Effectiveness of second-look endoscopy after gastric endoscopic submucosal dissection in patients taking antithrombotic agents: a multicenter propensity score matching analysis.

BACKGROUND: The risk of bleeding after gastric endoscopic submucosal dissection (ESD) in antithrombotic agent users has increased, and its management remains a problem. Second-look endoscopy (SLE) following gastric ESD in antithrombotic agent users may be effective in preventing delayed bleeding, but this requires elucidation. Therefore, this study aimed to investigate the efficacy of SLE in reducing bleeding after gastric ESD in patients receiving antithrombotic agents. METHODS: This retrospective cohort study was conducted at 19 referral hospitals in Japan. A total of 1,245 patients who were receiving antithrombotic agents underwent gastric ESD between January 2013 and July 2018. The incidence of delayed bleeding was compared between SLE and non-SLE groups using propensity score matching analysis. RESULTS: Overall, 858 patients (SLE group, 657 patients; non-SLE group, 201 patients) were analyzed. After matching, 198 pairs were created. Delayed bleeding occurred in 10 patients (5.1%) in the SLE group and 16 patients (8.1%) in the non-SLE group [odds ratio (OR) 0.605, 95% confidence interval (CI) 0.23-1.46, p = 0.310]. In the subgroup analysis, SLE reduced the incidence of delayed bleeding in patients receiving heparin bridging therapy (6.3% and 40.0%, respectively; p = 0.004). In the SLE group, prophylactic coagulation did not significantly reduce delayed bleeding compared to the no treatment group (14.6% and 8.6%, respectively; p = 0.140). CONCLUSIONS: SLE was ineffective in reducing bleeding after gastric ESD in antithrombotic agent users, overall. A prospective comparative study is warranted to definitively evaluate the effectiveness of SLE in reducing bleeding in high-risk patients.

Clinical Outcomes of Vonoprazan-Treated Patients after Endoscopic Submucosal Dissection for Gastric Neoplasms: A Prospective Multicenter Observation Study.

BACKGROUND: Vonoprazan (VPZ) has the potential to prevent delayed bleeding and promote ulcer healing after endoscopic submucosal dissection (ESD) similar to proton pump inhibitors (PPIs). OBJECTIVE: We aimed to evaluate the outcomes of VPZ-treated patients after ESD and compared the efficacy and feasibility in preventing a delayed bleeding and in healing an artificial ulcer after ESD between the VPZ and PPI therapies. METHODS: This was a prospective, observation study in 11 Japanese medical institutions. We enrolled and evaluated 223 patients who underwent gastric ESD followed by VPZ treatment (VPZ group). We selected 385 patients who underwent gastric ESD followed by PPI treatment as historical controls (PPI group) to compare the outcomes between the VPZ and PPI groups using a propensity score matching analysis. RESULTS: Among the 223 patients treated with VPZ, 173 were men and 50 were women with a median age of 72 years and with a median tumor size of 12.0 mm. Rates of en bloc resection and complete resection were 99.1 and 94.2%, respectively. Lymphovascular invasion was found in 6 (6.3%) cases. Intraoperative perforation and delayed bleeding occurred in 3 (1.3%) and 10 patients (4.5%), respectively. Scarring of artificial post-ESD ulcer was found in 153 patients (68.6%) at 6 weeks after ESD. The 205 pairs of propensity score-matched patients were comparable between the VPZ and PPI groups. The rate of delayed bleeding in the VPZ and PPI groups was 3.9 and 4.4%, respectively (difference, 0.5 percentage points; 95% confidence interval, -3.7 to 2.8%; non-inferiority, p = 0.01). Therefore, VPZ therapy demonstrated non-inferiority against PPI therapy in reducing the rate of delayed bleeding. The scar-stage ulcer at 6 weeks in the VPZ group and 8 weeks in the PPI group was 68.3 and 74.6%, respectively (p = 0.19). CONCLUSIONS: VPZ therapy showed an efficacy and feasibility in preventing a delayed bleeding after ESD similar to the PPI therapy. VPZ for 6 weeks and PPI for 8 weeks were similarly effective for an artificial ulcer healing after ESD.

[A case of pembrolizumab responding to recurrent small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome].

An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.

[A case of disseminated carcinomatosis of the bone marrow associated with gastric cancer developed 10 years after endoscopic submucosal dissection].

A 59-year-old man was treated for early gastric cancer with endoscopic submucosal dissection (ESD) 10 years prior to the study. Two months after the first ESD, he was diagnosed with recurrence on the ESD scar and treated via ESD again. The horizontal margin could not be evaluated because of cauterization, and the patient was carefully observed. He was admitted to our hospital complaining of low backache and diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer after examination. Although he started chemotherapy, he died after 6 months. In this study, we report a rare case of disseminated carcinomatosis of the bone marrow associated with gastric cancer, which developed 10 years after ESD.

[A case of Listeria meningitis with active ulcerative colitis and a review of literature in the Japanese cases].

A 53-year-old man who had been diagnosed with moderate ulcerative colitis and treated with mesalazine and glucocorticoid steroid was admitted due to fever of unknown origin and diarrhea. Intravenous feeding and treatment with cephem antibiotics were started, but the febrile reaction did not improve at all. Physical examination and various tests showed no specific symptoms, including headache or meningeal irritation. However, the blood culture test showed a positive result of Gram-positive bacilli. Thus, a lumbar puncture was performed and the patient was finally diagnosed with Listeria monocytogenes bacteremia and meningitis. Administration of intravenous meropenem and ampicillin led to the improvement of symptoms without any neurological sequelae. In addition, several cases with opportunistic infection of L. monocytogenes have been reported in recent years in cases of inflammatory bowel disease (IBD) during immunosuppressive therapy. Consequently, L. monocytogenes infection should be considered as one of differential diagnosis when patients present with IBD patient and are treated by biological or immunosuppressive agents with a fever of unknown origin.

Frequently abnormal serum gamma-glutamyl transferase activity is associated with future development of fatty liver: a retrospective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. METHODS: We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. RESULTS: The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. CONCLUSIONS: The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.

[Clinical Evaluation of the Efficacy and Adverse Effects of Nivolumab Treatment for Patients with Advanced Gastric Cancer].

BACKGROUND: Nivolumab, a fully human IgG4 monoclonal antibody inhibitor of programmed death-1(PD-1), was approved for use in the treatment of patients with advanced gastric or gastroesophageal junction cancer who had been previously treated with B2 chemotherapy regimens in Japan. METHODS: We investigated the efficacy of nivolumab therapy in 15 consecutive patients with advanced gastric cancer between October 2017 and December 2018 in our facility. RESULTS: In our study, the 6-month overall survival rate was 67.7%, and the median survival time(MST)was 6.3 months. Immune-related adverse events(irAEs)occurred in the following patients: 2 patients, interstitial pneumonia(13%); 1 patient, myocarditis (6.7%); 1 patient, hypothyroidism(6.7%); and 1 patient, liver dysfunction(6.7%). Of the patients with an absolute lym- phocyte count(ALC)of C2,000/mL at baseline, 33%(4/12)experienced irAEs, while of those with an ALC of >2,000/mL, 67% had irAEs. The 6-month overall survival rate was better in patients with an ALC >1,600/mL(100%, 4/4)than in those with an ALC of C1,600/mL(35%, 4/11). The 6-month overall survival rate of the patients with a neutrophil-to-lymphocyte ratio(NLR)of <4 was 63%, which was better than the 33% rate in those with an NLR of B4. CONCLUSIONS: Nivolumab therapy was a safe and feasible treatment option. The cutoff values of ALC of 2,000/mL for irAEs and of ALC of 1,600/mL and NLR of 4 for prognosis might be effective surrogate markers in nivolumab treatment.

[LECS-Assisted Open Partial Gastrectomy for an Ulcerative GIST in an Elderly Patient].

Laparoscopy and endoscopy cooperative surgery(LECS)is an excellent surgical procedure that prevents excessive resection of the gastrointestinal wall and maintains gastrointestinal functions. However, LECS is not recommended for large gastrointestinal stromal tumor(GIST)sized more than 5 cm and/or ulcerative GIST because of the oncological risk of peritoneal dissemination. Here, we report the case of an elderly patient who was successfully treated with LECS-assisted open partial gastrectomy for an ulcerative GIST near the esophagogastric junction.

Efficacy and safety of Helicobacter pylori eradication therapy immediately after endoscopic submucosal dissection.

BACKGROUND AND AIMS: In the treatment of patients after endoscopic submucosal dissection (ESD), there is no consensus on the optimum time to start Helicobacter pylori eradication therapy or on whether eradication therapy improves ulcer healing rate after ESD. The aim of this study was to examine the effect of immediate eradication of H. pylori on ulcer healing after ESD in patients with early gastric neoplasms. METHODS: A total of 330 patients who underwent ESD for early gastric neoplasms were enrolled. Patients were assigned to either H. pylori eradication group (Group A: H. pylori eradication + proton pump inhibitor 7 weeks) or non-eradication group (Group B: proton pump inhibitor 8 weeks). The primary end point was gastric ulcer healing rate (Group A vs Group B) determined on week 8 after ESD. RESULTS: Patients in Group A failed to meet non-inferiority criteria for ulcer scarring rate after ESD compared with that in Group B (83.0% vs 86.5%, P for non-inferiority = 0.0599, 95% confidence interval: -11.7% to 4.7%). There were, however, neither large differences between the two groups in the ulcer scarring rate nor the safety profile. CONCLUSIONS: This study failed to demonstrate the non-inferiority of immediate H. pylori eradication therapy after ESD to the non-eradication therapy in the healing rate of ESD-caused ulcers. However, because the failure is likely to attribute to small number of patients enrolled, immediate eradication therapy may be a treatment option for patients after ESD without adverse effects on eradication therapy in comparison with the standard therapy.

Helicobacter pylori Eradication Therapy Ameliorates Latent Digestive Symptoms in Chronic Atrophic Gastritis.

BACKGROUND/AIMS: This study investigated the effect of Helicobacter pylori eradication therapy on latent digestive symptoms in chronic atrophic gastritis. METHODS: We enrolled 650 health checkup patients who underwent eradication therapy for chronic gastritis and completed a self-report questionnaire before and after the treatment between January 2014 and December 2016 at the Japanese Red Cross Society Kyoto Daiichi Hospital. RESULTS: H. pylori eradication therapy for chronic atrophic gastritis improved latent digestive symptoms, including both the acid reflux and dyspepsia components in the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) scores. The effect was sustained until 1 year after the treatment. Higher FSSG scores (≥8 points) before H. pylori eradication therapy and age <70 years were significantly associated with the improvement of digestive symptoms after H. pylori eradication therapy. CONCLUSION: H. pylori eradication therapy may improve patients' quality of life through the resolution of latent abdominal symptoms.

[A case of freeze-dried gas gangrene antitoxin for the treatment of Clostridium perfringens sepsis].

A 66-year-old man was admitted to our hospital with high fever. We diagnosed a gas-containing liver abscess and performed percutaneous abscess drainage. However, 15 hours after admission, he developed massive intravascular hemolysis and acidosis. Sepsis due to Clostridium perfringens was suspected and we treated the patient intensively with multidisciplinary approaches, including antibiotics, mechanical ventilation, and renal replacement therapy. Furthermore, we administered freeze-dried gas gangrene antitoxin. Despite intensive care, the patient died 43 hours after admission.

A case of needle tract seeding with endoscopic findings of progression over time.

An 83-year-old male underwent three transgastric punctures with endoscopic ultrasound-guided fine-needle aspiration for the examination of a pancreatic body tumor. After a diagnosis of resectable pancreatic cancer and undergoing distal pancreatectomy, the patient was administered postoperative adjuvant chemotherapy with oral S-1 for 6 months, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were bimonthly evaluated. Carbohydrate antigen 19-9 levels continually increased to 4638.1 U/mL at 45 months post-fine-needle aspiration. Endoscopic ultrasound-guided showed a 25 mm low-echoic, irregularly shaped, and heterogeneous tumor with clear margins protruding from the mucosa outside the gastric wall, and biopsy confirmed adenocarcinoma. Since the immunostaining findings of the specimen matched those of the previously resected specimen, needle tract seeding (NTS) due to puncture of the pancreatic cancer was identified as the cause. After a pylorus-preserving gastrectomy at 46 months post-fine-needle aspiration, postoperative chemotherapy initiation, comprising gemcitabine and nab-paclitaxel, was initiated; however, the patient died despite these interventions as he developed multiple peritoneal dissemination. Although rare, the incidence of NTS will increase in the future owing to the expected extended survival in post-pancreatic cancer resection cases. We suggest regular upper gastrointestinal endoscopy and endoscopic ultrasound-guided evaluations for patients who are at risk for NTS can facilitate early detection. Furthermore, it is extremely relevant to share experiences of encountered NTS cases in practice and extend knowledge of its varying endoscopic appearances.

A case of disseminated peritoneal metastases after 2-year conservative treatment for intramucosal colon carcinoma due to a perforation during endoscopic submucosal dissection.

A 70-year-old man was admitted to our hospital for the treatment of a large granular-type laterally spreading tumor in the splenic flexure of the descending colon. The preoperative diagnosis was intramucosal colon carcinoma and endoscopic submucosal dissection was performed. During treatment, a small perforation occurred accidentally. After conservative treatment with endoscopic suturing, the patient was discharged without additional surgery. The pathological diagnosis was an intramucosal carcinoma. One year after treatment, no local recurrence was observed on endoscopy, and abdominal computed tomography showed no obvious metastasis. Two years later, fluorodeoxyglucose-positron emission tomography/computed tomography, laparoscopic findings, and histopathologic findings by experimental excision of omentum revealed several disseminated peritoneal metastases from previously treated colon carcinoma. To the best of our knowledge, this is the first report of peritoneal dissemination after a small perforation during endoscopic submucosal dissection and conservative therapy for early-stage colon carcinoma. This report suggests the possibility of tumor dissemination in patients with small perforations during endoscopic procedures. Endoscopists should be aware of these rare potential risks and perform later surveillance carefully.

Endoscopic submucosal dissection for undifferentiated early gastric cancer as the expanded indication lesion.

BACKGROUND: Endoscopic submucosal dissection (ESD) has become the standard endoscopic treatment for early gastric cancer without lymph node metastasis. At present, undifferentiated type intramucosal cancers without ulcer findings <20 mm in size are often chosen as endoscopic treatment lesions for expanded indication. The purpose of this study was to examine the outcome of ESD treatment in undifferentiated carcinomas. METHOD: Forty-six patients who had undergone ESD from July 2002 until July 2010, where the final pathological diagnosis was undifferentiated carcinoma, were assessed for the en-bloc resection ratio, the accuracy rate of depth or extent of diagnosis and survival. RESULTS: In endoscopic ultrasonography studies, the accuracy rate of mucosal lesions was 86%. The rate of en-bloc resection was 91% (42/46) and 5 cases had a positive margin. Four cases had a positive margin in cases of piecemeal resection. Five cases underwent additional surgery, and residual cancer was found in 1 case. There were 2 cases of perforation, 2 of delayed hemorrhage, and no cases of delayed perforation. One case died of multiple liver metastases and 1 died of hepatocellular carcinoma. After a maximum of 8 years, an average of 3.8 years of observation, including 7 cases who had undergone additional surgery, recurrence occurred in only 1 case of liver metastasis. CONCLUSION: In this study the lesions of undifferentiated adenocarcinoma, which were limited to the mucosa, <20 mm in diameter and had been completely resected, showed no recurrence and were indicated for endoscopic treatment.

Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis.

BACKGROUND AND AIMS: MicroRNA (miRNA) are endogenous, approximately 22-nucleotide non-coding RNA that suppress gene expression at post-transcriptional levels by binding to the 3'-untranslated region of specific mRNA targets through base-pairing. It has been recently reported that miRNA have critical functions in key biological processes such as cell proliferation and cell death in various cancer cells. However, the relationship between intestinal inflammation and miRNA expression remains unclear. In the present study, we used microarray technology to identify miRNA induced in the colonic mucosa of patients with active ulcerative colitis (UC). METHODS: Two colonic biopsy specimens from patients with active stage (>Matts grade 2) of UC under colonoscopy and two colonic biopsy specimens from healthy volunteers were obtained for gene expression profiles. Total RNA was extracted, and miRNA expression profiles were investigated using miRNA Microarray. Subsequently, to confirm the result of the Microarray investigation, we checked the expression of several selected miRNA using real-time polymerase chain reaction (PCR) in 12 colonic biopsy specimens from patients with active UC under colonoscopy and 12 specimens from the healthy volunteers. RESULTS: In the microarray study, the expression of several miRNA was upregulated in the colonic mucosa of patients with active UC. Furthermore, two miRNA (miR-21, miR-155) were selected in the study using real-time PCR. CONCLUSION: Upregulated miRNA may be responsible for the development of intestinal inflammation in UC.

Management of recurrence of symptoms of gastroesophageal reflux disease: synergistic effect of rebamipide with 15 mg lansoprazole.

BACKGROUND: Proton pump inhibitors (PPIs) are effective in healing reflux esophagitis and relieving the symptoms of gastroesophageal reflux disease (GERD). Prevention of recurrence of symptoms has become a therapeutic aim in patients with these conditions. AIMS: We investigated the effects of rebamipide, a mucosal protective anti-ulcer agent, on recurrence of reflux symptoms during PPI maintenance therapy. METHODS: Patients with esophagitis of Los Angeles classification A or B were treated with PPIs for 8 weeks. Patients with relief of symptoms were enrolled for further study. Forty-one patients were randomized to maintenance therapy with 15 mg of lansoprazole daily or 15 mg of lansoprazole and 300 mg rebamipide daily, and recurrence of symptoms was monitored over 12 months. In some patients, concentration of rebamipide and interleukin(IL)-8 expression in the esophageal mucosa were estimated. RESULTS: During the 12-month period, 11/20 patients (52.4%) taking lansoprazole 15 mg daily suffered recurrence of symptoms, compared to 4/20 patients (20%) treated with lansoprazole 15 mg and rebamipide 300 mg daily (P < 0.05). Rebamipide was detected in the esophageal mucosa 90-180 min after oral administration. IL-8 mRNA expression in the esophageal mucosa of patients with rebamipide was significantly decreased compared with that of patients without rebamipide. CONCLUSIONS: Combination therapy with rebamipide and lansoprazole appears to be highly effective in preventing recurrence of symptoms during long-term maintenance treatment for GERD.

Idiopathic hypereosinophilic syndrome with formation of multiple liver mass lesions.

We report a case of idiopathic hypereosinophilic syndrome (IHES) characterized by multiple liver mass lesions in an 82-year-old man. Numerous hypoechoic lesions were observed on ultrasonography and were mainly distributed in the S4, S6, and S7 segments. Plain computed tomography (CT) scans revealed low-density lesions. Dynamic CT images revealed arterial and portal vein branches passing through these lesions, with marginal areas enhanced during the arterial phase. The enhanced areas were extended during the portal venous phase. Contrast-enhanced ultrasonography (CEUS) images revealed enhanced vasculature in the early vascular phase. CEUS images obtained in the late vascular phase revealed enhanced areas containing microbubbles extended into the parenchyma; a prolonged enhancement pattern was observed. Kupffer-phase images revealed large portions of the lesion filled with microbubbles and a star-like defect at the center of the nodule. F18-2-fluoro-2-deoxyglucose (FDG) positron emission tomography/CT scans revealed intense FDG uptake by these lesions, which was similar to that by the segments S4, S6, and S7. Liver biopsy revealed diffused eosinophils infiltrated. The patient was closely followed up and was completely cured 11 weeks later without any treatment. This is a rare case of IHES with multiple liver mass lesions, which was well researched using multi-imaging equipment and cured without any treatment.

[A case of rectal GIST treated with imatinib mesylate neoadjuvant therapy to preserve the anus].

A 64-year-old man was admitted to our hospital with anal pain on evacuation. MRI revealed a large rectal submucosal tumor, more than 6 cm in diameter. Fine needle histological diagnosis indicated GIST with moderate risk. The patient was treated with imatinib mesylate in order to preserve the anus. The anal pain and tumor size decreased. Trans-anal local excision was performed. This case suggests that imatinib mesylate can make it possible to treat large rectal GIST cases by preserving anus, if neoadjuvant chemotherapy can be effective.

A Bile Duct Stone Formation around a Fish Bone as a Nidus after Pancreatoduodenectomy.

We report a rare case of bile duct stone formation around an ingested fish bone as a nidus after pancreatoduodenectomy. A 78-year-old woman was admitted to our department for fever and epigastric pain. Abdominal computed tomography revealed an elongated bile duct stone containing a linearly shaped foreign body of bone density. Enteroscopic lithotomy was performed using single balloon enteroscopy to safely remove the stone and foreign body from the bile duct. The foreign body was determined to be a fish bone by pathological examination and component analysis.