Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer

Purpose@#Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). @*Materials and Methods@#CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). @*Results@#In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). @*Conclusions@#CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

Cholecystitis after Placement of Covered Self-Expandable Metallic Stents in Patients with Distal Malignant Biliary Obstructions

Background/Aims@#Cholecystitis can occur after the placement of covered self-expandable metallic stents for distal malignant biliary obstructions. We aimed to identify risk factors for cholecystitis following covered self-expandable metallic stent placement. @*Methods@#We investigated risk factors related to cholecystitis following covered self-expandable metallic stent placement in 118 patients with distal malignant biliary obstructions between January 1, 2015 and April 30, 2019. Endoscopic assessments and tumor invasion to the arteries feeding the gallbladder were determined by a pancreaticobiliary endoscopist and a radiologist, respectively. @*Results@#The median patient age was 72 years (men, 61.0%). The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct were observed in 35 (29.7%) and 35 (29.7%) patients, respectively. During the observation period (median, 179 days), cholecystitis occurred in 18 (15.3%) patients. Multivariate analysis revealed the flow of the contrast agent into the gallbladder (p=0.023) and tumor involvement in the orifice of the cystic duct (p=0.005) as significant independent risk factors associated with cholecystitis. @*Conclusions@#The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct are potential independent risk factors for cholecystitis following the placement of covered self-expandable metallic stents. A follow-up prospective study is warranted to validate their influence.

Cholecystitis after Placement of Covered Self-Expandable Metallic Stents in Patients with Distal Malignant Biliary Obstructions

Background/Aims@#Cholecystitis can occur after the placement of covered self-expandable metallic stents for distal malignant biliary obstructions. We aimed to identify risk factors for cholecystitis following covered self-expandable metallic stent placement. @*Methods@#We investigated risk factors related to cholecystitis following covered self-expandable metallic stent placement in 118 patients with distal malignant biliary obstructions between January 1, 2015 and April 30, 2019. Endoscopic assessments and tumor invasion to the arteries feeding the gallbladder were determined by a pancreaticobiliary endoscopist and a radiologist, respectively. @*Results@#The median patient age was 72 years (men, 61.0%). The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct were observed in 35 (29.7%) and 35 (29.7%) patients, respectively. During the observation period (median, 179 days), cholecystitis occurred in 18 (15.3%) patients. Multivariate analysis revealed the flow of the contrast agent into the gallbladder (p=0.023) and tumor involvement in the orifice of the cystic duct (p=0.005) as significant independent risk factors associated with cholecystitis. @*Conclusions@#The flow of the contrast agent into the gallbladder and tumor involvement in the orifice of the cystic duct are potential independent risk factors for cholecystitis following the placement of covered self-expandable metallic stents. A follow-up prospective study is warranted to validate their influence.

Pancreatic granular cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration biopsy.

Pancreatic granular cell tumors (GCTs) are rare and making an imaging diagnosis of pancreatic GCT is difficult because it has no definite characteristics on contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging (MRI) owing to varying findings. We report about a 32-year-old woman who presented with an incidental finding of a pancreatic tumor with a past history of excision of a right forearm GCT nodule 12 years ago. CE-CT revealed a 23-mm-sized homogeneous low enhancement tumor in the arterial phase in the pancreatic body. Abdominal MRI revealed a lobulated hypointense mass in T1WI and high signal in DWI. Endoscopic ultrasonography (EUS) revealed that the tumor was oval, hypoechoic with posterior echo enhancement, and had a well-defined border. Although EUS-guided fine needle aspiration revealed benign granular cells of the pancreas, she underwent laparoscopic surgery because the metastatic tumor from the past lesion was not excluded. The pathological finding was benign GCT of the pancreas and it was considered as an original lesion. In the previous reports, most of the resected cases were considered to be pancreatic cancer or neuroendocrine tumor preoperatively. Compared to CE-CT and MRI, EUS imaging and EUS-FNA are more reliable diagnosis tools for pancreatic GCT. Although malignant GCT accounts for approximately 1-2% of all cases, surgical resection or strict follow-up should be considered because it is difficult to predict its biological behavior.

Analysis of the diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in patients with a suspected pancreatic malignanc

Objectives: to determine the diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) for suspected pancreatic malignancy. As well as to identify factors that affect the incidence of false-negative cases and evaluate the value of repeated EUS-FNA in patients with inconclusive results. Methods: we retrospectively evaluated the data of patients who underwent EUS-FNA due to a suspected pancreatic malignancy in our hospital from January 2015 to December 2016. Results: a total of 194 EUS-FNA procedures performed and 175 cases were analyzed. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 83.4% (151/181), 100% (13/13), 100% (151/151), 30.2% (13/43), and 84.5% (164/194), respectively. The combination of cytological and histological examination significantly increased the diagnostic performance compared to either method alone. The diagnostic sensitivity in metastatic tumors was significantly lower than that for adenocarcinoma. EUS-FNA performed using standard needles combined with the "slow-pull" technique had a lower sensitivity than other methods. According to the multivariate analysis, neither the combination of needle type and suction technique nor final diagnosis were independent factors that affected the diagnostic sensitivity. The sensitivity of repeated EUS-FNA was 50.0% (8/16). Definitive results after a repeated puncture were more likely for pancreatic body and tail masses, heterogeneous lesions and poorly demarcated lesions. However, the difference was not significant. Conclusions: EUS-FNA was accurate for the evaluation of a suspected pancreatic malignancy. Metastatic tumors and the use of a standard needle in combination with the slow-pull technique may increase the incidence of false-negative results. Repeated EUS-FNA has limited value but should be considered for selected cases where the suspicion of malignancy persists

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Analysis of the diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration in patients with a suspected pancreatic malignancy.

OBJECTIVES: to determine the diagnostic yield of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) for suspected pancreatic malignancy. As well as to identify factors that affect the incidence of false-negative cases and evaluate the value of repeated EUS-FNA in patients with inconclusive results. METHODS: we retrospectively evaluated the data of patients who underwent EUS-FNA due to a suspected pancreatic malignancy in our hospital from January 2015 to December 2016. RESULTS: a total of 194 EUS-FNA procedures performed and 175 cases were analyzed. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 83.4% (151/181), 100% (13/13), 100% (151/151), 30.2% (13/43), and 84.5% (164/194), respectively. The combination of cytological and histological examination significantly increased the diagnostic performance compared to either method alone. The diagnostic sensitivity in metastatic tumors was significantly lower than that for adenocarcinoma. EUS-FNA performed using standard needles combined with the "slow-pull" technique had a lower sensitivity than other methods. According to the multivariate analysis, neither the combination of needle type and suction technique nor final diagnosis were independent factors that affected the diagnostic sensitivity. The sensitivity of repeated EUS-FNA was 50.0% (8/16). Definitive results after a repeated puncture were more likely for pancreatic body and tail masses, heterogeneous lesions and poorly demarcated lesions. However, the difference was not significant. CONCLUSIONS: EUS-FNA was accurate for the evaluation of a suspected pancreatic malignancy. Metastatic tumors and the use of a standard needle in combination with the slow-pull technique may increase the incidence of false-negative results. Repeated EUS-FNA has limited value but should be considered for selected cases where the suspicion of malignancy persists.

Roles of Capsule Endoscopy and Single-Balloon Enteroscopy in Diagnosing Unexplained Gastrointestinal Bleeding

BACKGROUND/AIMS: The diagnostic algorithms used for selecting patients with obscure gastrointestinal bleeding (OGIB) for capsule endoscopy (CE) or balloon-assisted enteroscopy (BE) vary among facilities. We aimed to demonstrate the appropriate selection criteria of CE and single balloon-assisted enteroscopy (SBE) for patients with OGIB according to their conditions, by retrospectively comparing the diagnostic performances of CE and BE for detecting the source of the OGIB. METHODS: We investigated 194 patients who underwent CE and/or BE. The rate of positive findings, details of the findings, accidental symptoms, and hemostasis methods were examined and analyzed. RESULTS: CE and SBE were performed in 103 and 91 patients, respectively, and 26 patients underwent both examinations. The rate of positive findings was significantly higher with SBE (73.6%) than with CE (47.5%, p<0.01). The rate of positive findings was higher in overt bleeding cases than in occult bleeding cases for both BE and SBE. Among the overt bleeding cases, the rate was significantly higher in ongoing bleeding cases than in previous bleeding cases. CONCLUSIONS: Both CE and SBE are useful to diagnose OGIB. For overt bleeding cases and ongoing bleeding cases, SBE may be more appropriate than CE because endoscopic diagnosis and treatment can be completed simultaneously.

Recent Advances of Biliary Stent Management

Recent progress in chemotherapy has prolonged the survival of patients with malignant biliary strictures, leading to increased rates of stent occlusion. Even we employed metallic stents which contributed to higher rates and longer durations of patency, and occlusion of covered metallic stents now occurs in about half of all patients during their survival. We investigated the complication and patency rate for the removal of covered metallic stents, and found that the durations were similar for initial stent placement and re-intervention. In order to preserve patient quality of life, we currently recommend the use of covered metallic stents for patients with malignant biliary obstruction because of their removability and longest patency duration, even though uncovered metallic stents have similar patency durations.

[Clinical development of S-1 (TS-1) for advanced gastric cancer].

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.