Feasibility of Endoscopic Screening for Upper Gastrointestinal Malignancy in a Comprehensive Health Checkup.

Objective In an effort to reduce mortality from gastric cancer, endoscopic screening was introduced in 2016 as a nationwide screening program in Japan. Recent developments in high-definition endoscopic imaging and diagnostic strategies have enabled the simultaneous detection of other upper gastrointestinal (U-GI) malignancies. Therefore, we conducted a study to evaluate the feasibility of endoscopic screening for U-GI malignancy in a comprehensive health checkup. Methods We retrospectively reviewed the data of 13,120 participants who had received a comprehensive health checkup in a single institution between April 2012 and March 2018. Participants were divided into two groups [gastrointestinal endoscopy (GIE) group (n=9,142) and gastrointestinal X-ray (X-ray) group (n=3,978)] and compared with regards to the screening results, adverse events, and detection rate of U-GI malignancies (gastric cancer or other) using a propensity-score matched analysis. Results The gastric cancer detection rate was significantly higher in the GIE group [34/9,142 (0.48%)] than in the X-ray group [3/3,978 (0.08%)] (p=0.003). Other U-GI malignancies were found only in the GIE group and comprised two hypopharyngeal cancers, five esophageal cancers, two duodenal cancers, and one duodenal gastrointestinal stromal tumor. Adverse events occurred in 6/9,142 (0.07%) participants in the GIE group and 18/3,978 (0.45%) participants in the X-ray group (p<0.0001). A propensity-score matched analysis yielded 1,551 matched pairs, and the detection rate of gastric cancer and other U-GI malignancies remained significantly higher in the GIE group than in the X-ray group. Conclusion This study indicated that not only gastric cancer but also other U-GI malignancies can be detected by endoscopic screening.

Feasibility of gastric endoscopic submucosal dissection without using proton pump inhibitor injection: a propensity score analysis.

Purpose: Endoscopic submucosal dissection is a promising method for the resection of superficial gastric neoplasms. To date, several institutions have used proton pump inhibitor injections over the perioperative period. However, there is very little evidence regarding their efficacy. To overcome this limitation, we compared procedural outcomes and the prevention of adverse events of proton pump inhibitor injection with an orally administered active potassium-competitive acid blocker alone. Participants and Methods: We enrolled a total of 150 patients treated for superficial gastric neoplasms at a single institution between April 2015 and December 2018. Patients treated for 2 days with proton pump inhibitor injections following 12 days of oral potassium-competitive acid blocker (proton pump inhibitor group=80) were compared with patients treated for 14 days orally with potassium-competitive acid blocker alone (potassium-competitive acid blocker group=70) using propensity score analysis. We evaluated intragastric pH levels prior to endoscopic submucosal dissection, frequency of intraoperative major bleeding, procedure time, en bloc resection rate, curability, ulcer reduction rate 14 days after endoscopic submucosal dissection, and adverse events (including perforation and postoperative bleeding). Results: Propensity score analysis yielded 43 matched pairs. The comparison demonstrated similar values for the outcomes. For all cases, we observed intragastric pH levels >6.4 prior to endoscopic submucosal dissection. Postoperative bleeding rates were 2.3% (1/43) in the proton pump inhibitor group and 0.0% (0/43) in the potassium-competitive acid blocker group (P=0.315). Conclusions: Oral potassium-competitive acid blocker alone was as effective as proton pump inhibitor injection, with a low incidence of adverse events. Based on these results, proton pump inhibitor injection might be omitted during gastric endoscopic submucosal dissection.

Effect of Continued Administration of Low-dose Aspirin for Intraoperative Bleeding Control in Gastric Endoscopic Submucosal Dissection.

BACKGROUND: The use of antithrombotic agents for the prevention of cerebro-cardioembolic events has increased, and recent guidelines have recommended the continued administration of low-dose aspirin (LDA) during endoscopic procedures with a high risk of bleeding. However, the influence of LDA on intraoperative bleeding control status during Endoscopic submucosal dissection (ESD) remains unclear. METHODS: We examined 293 consecutive patients who underwent ESD for gastric cancers between January 2014 and February 2018. Patients administered with LDA (n = 52) were compared with those without antithrombotic therapy (n = 241; control) by propensity-score matching (PSM) concerning outcomes of ESD. RESULTS: PSM analysis yielded 50 matched pairs. Comparison showed similar values for frequency of intraoperative major bleeding: 1 (0-4) times (median [range]) in the LDA group and 0 (0-5) in the control group respectively (p = 0.710). Others (frequency of preventive coagulation, procedure time, decrease of hemoglobin levels, en bloc resection, complete resection) were the same with a few adverse events including perforation (0%), and thromboembolism (0%). Postoperative bleeding rate was 1.9% in LDA group. Multivariate analysis indicated that location U and circumference on the posterior wall were associated with for multiple major intraoperative bleeding. CONCLUSION: The study suggests that gastric ESD can be safely accomplished without cessation of LDA.

Short-term efficacy of potassium-competitive acid blocker following gastric endoscopic submucosal dissection: a propensity score analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a promising method for the resection of superficial gastric neoplasms. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that is currently considered as a potential alternative to proton pump inhibitors (PPIs) for the treatment of acid-related diseases. However, the utility of vonoprazan in ESD-related ulcers is unclear. Therefore, we compared the short-term efficacies of vonoprazan and the PPI lansoprazole in ESD-related ulcer healing during the first two weeks following intervention. METHODS: This study included 115 superficial gastric neoplasms that were treated by ESD at Hiraka General Hospital between April 2015 and January 2017. Patients treated with P-CAB (20 mg vonoprazan, n = 62) or PPI (30 mg lansoprazole, n = 53) were compared using propensity-score matching analysis. Primary outcome was rate of ulcer reduction at two weeks after ESD. Secondary outcomes were coverage ratio of ulcer base by granulation tissue and incidence of postoperative bleeding. RESULTS: The rate of ulcer reduction was significantly higher (median [range], 80.6% [67.6%-94.5%] vs. 62.7% [33.4%-85.2%]; p < .0001) and coverage ratio of the ulcer base by granulation tissue was significantly accelerated (median [range], 84.1% [67.7%-95.3%] vs. 61.9% [12.1%-90.1%]; P < 0.0001) in the P-CAB group compared with the PPI group. Postoperative bleeding was not observed in either group. CONCLUSIONS: P-CAB achieved rapid artificial ulcer healing with promotion of granulation tissue formation. However, conventional PPI with initial intravenous infusion might be sufficient for prevention of postoperative bleeding following gastric ESD.

Feasibility of Knife-Coagulated Cut in Gastric Endoscopic Submucosal Dissection: A Case-Control Study.

BACKGROUND/AIMS: Intraoperative bleeding remains a challenge during endoscopic submucosal dissection (ESD). Forceps-coagulated cut (FCC) was found to be effective to reduce this bleeding. However, this involved frequent device replacement, and therefore, knife-coagulated cut (KCC) might ensure an easier and smoother procedure. We aimed to assess the effectiveness of KCC with Flushknife-BT at a super-low-output setting. METHODS: In this prospective study, we compared the hemostasis condition during ESD in 40 pairs of gastric lesions treated by FCC (Group F) or KCC (Group K). The primary outcome was frequency of major bleeding with an analysis by tumor location. The secondary outcomes included frequency of exchanging devices, procedure time, en bloc resection rate, and adverse event rate. RESULTS: In terms of the frequency of major bleeding, there was no significant difference between Group F and K (0.95 ± 0.12 vs. 0.88 ± 0.17, p = 0.282). Lesions located on the upper third of the stomach involved repeated hemostasis (p = 0.012). The frequency of exchanging devices was higher in Group F than in Group K (6.95 ± 0.42 vs. 0.88 ± 0.17, p = 0.000). Procedure time was reduced in Group K by 15.6%. Other aspects were the same in both groups. CONCLUSION: KCC prevented intraoperative bleeding just as FCC did. But it decreased device replacement and saved time and only a low risk was involved. This technique could ensure the conduct of a smooth and safe procedure during gastric ESD. UMIN000017229.

Proper muscle layer damage affects ulcer healing after gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is the established therapy for superficial gastrointestinal neoplasms. However, management of the artificial ulcers associated with ESD has become important and the relationship between ulcer healing factors and treatment is still unclear. We aimed to evaluate ESD-related artificial ulcer reduction ratio at 4 weeks to assess factors associating with ulcer healing after ESD that may lead to optimal treatment. METHODS: Between January 2009 and December 2013, a total of 375 lesions fulfilled the expanded criteria for ESD. We defined ulcer reduction rate <90% as (A) poor-healing group; and rate ≥90% as (B) well-healing group. After exclusion, 328 lesions were divided into two groups and analyzed. These two groups were compared based on clinicopathological/endoscopic features, concomitant drugs, and treatment. RESULTS: Ulcer reduction rate was significantly correlated with factors related to the ESD procedure (i.e. procedure time, submucosal fibrosis, and injury of the proper muscle layer, in univariate analysis. Multivariate logistic regression analysis showed that submucosal fibrosis (F2) (P = 0.03; OR, 16.46; 95% CI, 1.31-206.73) and injury of the proper muscle layer (P = 0.01; OR, 4.27; 95% CI, 2.04-8.92) were statistically significant predictors of delayed healing. CONCLUSION: This single-center retrospective study indicated that ESD-induced artificial ulcer healing was affected by submucosal fibrosis and injury of the proper muscle layer, which induced damage to the muscle layer. Therefore, the preferable pharmacotherapy can be determined on completion of the ESD procedure.

Prospective randomized controlled study comparing cell block method and conventional smear method for pancreatic juice cytology.

AIM: To elucidate the diagnostic efficacy of the cell block (CB) method by comparing it with that of conventional smear cytology for pancreatic juice obtained by endoscopic retrograde cholangiopancreatography (ERCP) in a randomized controlled trial fashion. METHODS: A total of 170 patients with pancreatic lesions suspicious of being malignant who underwent pancreatic juice collection without giving secretin under ERCP were enrolled in this study. After sampling, the pancreatic juice was randomized to the CB method (n = 85) or to smear cytology (n = 85). CB sections were subjected to hematoxylin-eosin, periodic acid Schiff-Alcian blue, and immunohistochemical stains. Both Papanicolaou stain and Giemsa stain were used for smear cytology. RESULTS: The final diagnosis was malignancy in 54 patients: pancreatic cancer, 45; intraductal papillary-mucinous carcinoma, six; and endocrine tumor, three. The number of patients with a cytological borderline malignancy in the CB group (3.5%) was significantly smaller than that in the smear group (27.1%) (P < 0.001). The diagnostic accuracy of the CB method and that of smear cytology were 76.5% (65/85) and 74.1% (63/85), respectively (P = 0.72), and their respective sensitivities were 50% (14/28) and 38.5% (10/26) (P = 0.39). The sensitivity of the CB method (88.9%) was better than that of smear cytology (42.9%) for invasive ductal carcinoma in the pancreas head (P = 0.048). CONCLUSIONS: The CB method using immunostaining for pancreatic juice cytology showed a much lower rate of equivocal borderline malignancy and a tendency for a higher diagnostic yield compared with smear cytology. Its diagnostic sensitivity, however, was not satisfactory except for pancreatic-head cancer.

[A case of mucinous cystadenoma of the pancreas resected after a 10-year follow-up].

A 40-year-old woman was hospitalized because of acute pancreatitis. CT showed a monolocular cyst thought to be a pseudocyst. The patient was followed as an outpatient. The size of the cyst decreased 6 years later. Ultrasonography 10 years later demonstrated an enlarged cyst with a cyst-in-cyst formation. A tendency to increase in size and the irregular wall thickening indicated that the cyst was a malignant mucinous cystic neoplasm (MCN) and distal pancreatectomy was performed. The tumor was diagnosed histologically as a mucinous cystadenoma. A case of MCN resected after long-term follow-up is extremely rare. The present case is thought to be important for elucidation of the natural history of MCNs.

Lateral spread along the main pancreatic duct in branch-duct intraductal papillary-mucinous neoplasms of the pancreas: usefulness of intraductal ultrasonography for its evaluation.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend to spread intraepithelially along the pancreatic duct wall. We evaluated histopathological intraductal lateral spread (LS) along the main pancreatic duct (MPD) from branch-duct IPMN and investigated the usefulness of intraductal ultrasonography (IDUS) for its preoperative diagnosis. PATIENTS AND METHODS: Twenty-four patients with branch-duct IPMN who had undergone preoperative IDUS and surgery were reviewed clinicopathologically. The prevalence and histological length of LS along the MPD from branch-duct IPMN, characteristics of the patients with LS, and efficacy of LS assessment by IDUS were examined. RESULTS: LS along the MPD was observed in 54% of the subjects. In the group of patients with LS, its mean length was 25.2±16.8mm (5-50mm) and the diameter of the MPD was 6mm or greater. Of the patients with LS, those in whom the length of LS along the MPD was longer than the diameter of the cystically dilated branch accounted for 30%. The diameter of the MPD in the group with LS was significantly greater than that in the group without LS (P=0.03). The sensitivity, specificity, and overall accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively. CONCLUSION: LS along the MPD was detected in about half of the resected cases of branch-duct IPMN. Preoperative transpapillary IDUS may be beneficial for the determination of the resection line, especially in those branch-duct IPMN patients in whom the MPD is 6 mm or greater in diameter.

Single-session endoscopic bilateral y-configured placement of metal stents for hilar malignant biliary obstruction.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of endoscopic bilateral biliary metal stent placement for hilar malignant obstruction. PATIENTS AND METHODS: Twenty patients with unresectable malignant hilar biliary obstruction who had undergone endoscopic bilateral Y-configured biliary drainage with metal stents were enrolled as a study group (YMS group). Thirty-seven patients who had undergone bilateral drainage with plastic stents were selected as a historical control (PS group). Two newly designed metal stents for bilateral Y-configured placement were endoscopically deployed in a partial stent-in-stent manner in one session. Technical success, early complications, and stent patency were evaluated. RESULTS: The technical success rate in the YMS group was 100%. Mild post-endoscopic retrograde cholangiopancreatography pancreatitis occurred in one patient in the YMS group and in two in the PS group. The success rate of biliary decompression was 95% in the YMS group and 89% in the PS group (P=0.65). During a median follow-up period of 7.3months, the incidence of stent occlusion in the YMS group was significantly lower than that in the PS group (30% vs 62%, P=0.028). Mean stent patency in the YMS group was 250days and that in the PS group was 115days (P=0.0061). Risk factors for stent occlusion were bile duct cancer (P=0.035) and the PS group (P=0.07) by multivariate analysis. CONCLUSION: Single-session endoscopic bilateral biliary placement of newly designed metal stents for hilar malignant obstruction is safe and useful with a high technical success rate and a long patency period.

A case of early carcinoma of the papilla of Vater confined to the mucosa and continuative epithelium of glands in Oddi's sphincter (m-God) treated by endoscopic papillectomy.

We herein report a case of early stage ampullary cancer, treated by endoscopic papillectomy, in which tumor extension was confined to the mucosa and adjacent epithelium of the glands in Oddi's sphincter. A 77-year-old man underwent screening esophagogastroduodenoscopy, which revealed a mass in the papilla of Vater, which was well-differentiated adenocarcinoma as proven by biopsy. The tumor was diagnosed as T1 and endoscopic papillectomy was performed. Histological examination showed adenocarcinoma limited to the mucosa of the common channel and continuative epithelium of the neighboring glands in Oddi's sphincter. No signs of recurrence have been observed during a follow-up of 23 months.

Newly developed fully covered metal stent for unresectable malignant biliary stricture.

We herein report two patients with unresectable malignant biliary stricture who underwent stenting with a newly developed fully-covered metal stent. In the first case of lower-middle bile duct cancer, a stent was placed through the stenosis. In the second case of middle bile duct stricture due to lymph node metastases from gallbladder cancer, a stent was placed in the bile duct across the stenosis. No procedure-related complications were observed. Unevenness of the outer surface and a low shortening ratio are expected to lessen the occurrence of complications characteristic of covered metal stents such as stent migration and bile duct kinking.

Endosonography-guided biliary drainage with one-step placement of a newly developed fully covered metal stent followed by duodenal stenting for pancreatic head cancer.

An 83-year-old man was admitted to our department, presenting with jaundice, fever, and nausea. CT revealed a pancreatic head tumor with duodenal invasion. Endoscopic transpapillary biliary drainage was unsuccessful due to stenosis at the second portion of the duodenum and tumor invasion to the papilla of Vater. Using a convex linear array echoendoscope, a fully-covered metal stent was placed across the puncture tract to bridge the duodenum and the bile duct. After improvement of jaundice, a duodenal metal stent was placed across the stricture of the duodenum. No procedure-related complications occurred. Neither migration nor obstruction of the two stents was observed during the three months followup period. Combination of ESBD using a fully covered metal stent and duodenal stenting is a feasible technique and possibly a less invasive treatment option for malignant biliary and duodenal obstruction compared to surgery.

Efficacy and safety of therapeutic ERCP for the elderly with choledocholithiasis: comparison with younger patients.

OBJECTIVE: To clarify the efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography for the elderly with choledocholithiasis compared with younger patients. METHODS: Consecutive therapeutic ERCPs performed between 2005 and 2007 at our institution for 118 patients aged 80 years or older (group A) and 205 patients younger than 80 years old (group B) were retrospectively reviewed. Successful cannulation rate, complete stone clearance rate, complications and prognosis were compared between the two groups. RESULTS: Successful cannulation was achieved in 99.2% in group A versus 99.5% in group B. The complete stone clearance rate was significantly lower in group A than in group B (92.4% versus 99.0%, p<0.01). Plastic stent placement was performed for patients with incomplete duct clearance. There was no significant difference in the early complication rate between group A (5.5%) and group B (6.6%). Procedure-related mortality did not occur. Cholangitis-free survival was similar between the two groups. The short-term prognosis was comparable between those with complete duct clearance and those with biliary stent placement. CONCLUSION: With a duct clearance rate of more than 90% and plastic stent placement for patients with poor general condition, therapeutic ERCP for choledocholithiasis in patients 80 years of age or older is comparable in safety and effectiveness to that in younger patients.

Intraductal papillary mucinous neoplasms of the pancreas showing fistula formation into other organs.

BACKGROUND: This study assessed the mechanism of fistula formation in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: A total of 274 patients with IPMN who had been diagnosed by endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography (EUS) at our center were enrolled. The patients with IPMN which had fistula formation into other organs were investigated retrospectively as to (1) clinical prevalence and the organs penetrated by IPMN, (2) analysis of the mechanism of fistula formation by immunohistopathological study, (3) efficacy of EUS in progression assessment, and (4) prognosis. RESULTS: Among the subjects, fistula formation into other organs was observed in 18 patients (6.6%) and into 28 organs. There were 7 patients (39%) in whom multiple organs were penetrated. Of 16 patients who had undergone investigation of the expression of mucin markers, 94% had an intestinal-type tumor. Of 9 patients who had undergone surgery or autopsy, 67% showed mechanical penetration without invasion around the fistula. Only papillary protrusions were seen by EUS in 4 of these patients with noninvasive papillary adenocarcinoma showing mechanical penetration. All 5 patients who had pancreatic parenchymal invasion showed a mass with a mixed-echo pattern in addition to papillary protrusions shown by EUS, corresponding to colloid carcinoma. CONCLUSIONS: There were 2 processes in the development of fistulas in IPMN. Of those patients showing fistula formation, 94% had intestinal-type IPMN, and 67% showed mechanical penetration. Delineation of a mass with the mixed-echo pattern suggested an invasive penetration due to colloid carcinoma.