Prospective comparison of diagnostic performance of magnifying endoscopy and biopsy for sessile serrated adenoma/polyp.

Background: Magnifying narrow-band imaging (M-NBI) has recently improved the accuracy of endoscopic diagnosis of gastrointestinal tumors, including colorectal polyps. However, it can be difficult to distinguish between sessile serrated adenoma/polyps (SSA/Ps) and other polyps, especially hyperplastic polyps (HPs), by histological biopsy, because diagnostic features of SSA/Ps can be detected around the colon crypt bases. We aimed to evaluate the accuracy of endoscopic diagnosis of SSA/Ps using M-NBI compared with histological biopsy. Methods: We prospectively enrolled patients diagnosed with SSA/Ps by preoperative endoscopy and assessed the diagnostic accuracy. The primary outcome was the diagnostic accuracy of endoscopy and biopsy. Results: Between August 2015 and October 2017, 295 lesions were resected by polypectomy or endoscopic mucosal resection, and 79 endoscopically resected specimens that were endoscopically diagnosed as SSA/P underwent biopsy for histological examination. Two lesions were excluded because the specimens were too small for histological examination. Finally, 77 endoscopically resected specimens and 77 biopsy specimens were included in the analysis. Histopathological examination showed 67 SSA/Ps, 8 HPs, and 2 adenomas. The sensitivity, specificity and accuracy of endoscopic M-NBI diagnosis for SSA/Ps were 95.7%, 95.5% and 95.6%, respectively. The sensitivity, specificity and accuracy of histological diagnosis of a single biopsy specimen were 71.6%, 90.0% and 74.0%, respectively. The McNemar test showed significant differences between biopsy and endoscopy diagnoses (P=0.001). Conclusion: This study shows that biopsy may be avoided by using M-NBI in patients with suspected SSA/Ps.

Gastric Hyperplastic Polyps Can Shrink After Discontinuation of Proton Pump Inhibitors: A Case Series Compared With Continuation of Proton Pump Inhibitors.

GOAL: This study investigated whether gastric hyperplastic polyps (GHPs) shrink after discontinuation of proton pump inhibitor (PPI) alone. BACKGROUND: Long-term use of PPIs has been reported to increase the incidence of GHPs, which sometimes bleed and cause anemia. We experienced a patient whose recurrent hemorrhagic GHPs associated with long-term use of PPIs had disappeared after discontinuation of PPIs. STUDY: This study was conducted retrospectively at Kyoto University Hospital. Patients with histologically confirmed GHPs who had been taking PPIs for >6 months and who had undergone a repeat endoscopy within 2 years were included. Polyp shrinkage was defined as the disappearance of polyps or a reduction of >50% in the long diameter of the largest polyp. RESULTS: Six patients who discontinued PPIs were compared with 17 patients who continued PPIs. Polyp shrinkage was significantly more frequent in the PPI-discontinuation group (5/6, 83%) than in the PPI continuation group (0/17, 0%) (P<0.001). In 2 patients in the PPI-discontinuation group, the polyps completely disappeared finally. CONCLUSION: These findings suggest that discontinuation of PPIs can shrink GHPs in patients using PPIs.

Efficacy of Underwater Endoscopic Mucosal Resection for Nonpedunculated Colorectal Polyps: A Systematic Review and Meta-Analysis.

Recently, underwater endoscopic mucosal resection (UEMR) without submucosal injection was introduced as a new replacement for conventional EMR (CEMR) and was reported to be useful for resecting large colonic polyps. Here, we aimed to assess the efficacy and safety of these two methods by a systematic review and meta-analysis. We comprehensively searched multiple databases until July 2021 to identify randomized controlled trials (RCTs) comparing UEMR with CEMR. The primary outcomes were the proportion of R0 resection and mean procedure time, and the secondary outcomes were the proportion of en bloc resection and all adverse events. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in www.protocols.io (Protocol Integer ID: 40849). We included six RCTs (1,374 polyps). We judged that a meta-analysis was not available, and the data were summarized narratively for the proportion of R0 resection. Regarding procedure time, UEMR likely resulted in a large reduction (mean difference = -64.3 seconds; 95% confidence interval (CI) = -122.5 to -6.0 seconds; I2 = 86%; moderate certainty of evidence). UEMR likely resulted in a large increase in en bloc resection (odds ratio = 1.85; 95% CI = 1.15 to 2.98; I2 = 60%; moderate certainty of evidence). Percentages of adverse events were 0-17% with CEMR and 0-16% with UEMR. In summary, UEMR might have higher efficacy than CEMR in the endoscopic resection of nonpedunculated colorectal polyps, with likely a large reduction in procedure time.

Indolent feature of Helicobacter pylori-uninfected intramucosal signet ring cell carcinomas with CDH1 mutations.

BACKGROUND: In Helicobacter pylori (Hp)-uninfected individuals, diffuse-type gastric cancer (DGC) was reported as the most common type of cancer. However, the carcinogenic mechanism of Hp-uninfected sporadic DGC is largely unknown. METHODS: We performed whole-exome sequencing of Hp-uninfected DGCs and Hp-uninfected normal gastric mucosa. For advanced DGCs, external datasets were also analyzed. RESULTS: Eighteen patients (aged 29-78 years) with DGCs and nine normal subjects (28-77 years) were examined. The mutation burden in intramucosal DGCs (10-66 mutations per exome) from individuals aged 29-73 years was not very different from that in the normal gastric glands, which showed a constant mutation accumulation rate (0.33 mutations/exome/year). Unbiased dN/dS analysis showed that CDH1 somatic mutation was a driver mutation for intramucosal DGC. CDH1 mutation was more frequent in intramucosal DGCs (67%) than in advanced DGCs (27%). In contrast, TP53 mutation was more frequent in advanced DGCs (52%) than in intramucosal DGCs (0%). This discrepancy in mutations suggests that CDH1-mutated intramucosal DGCs make a relatively small contribution to advanced DGC formation. Among the 16 intramucosal DGCs (median size, 6.5 mm), 15 DGCs were pure signet ring cell carcinoma (SRCC) with reduced E-cadherin expression and a low proliferative capacity (median Ki-67 index, 2.4%). Five SRCCs reviewed endoscopically over 2-5 years showed no progression. CONCLUSIONS: Impaired E-cadherin function due to CDH1 mutation was considered as an early carcinogenic event of Hp-uninfected intramucosal SRCC. Genetic and clinical analyses suggest that Hp-uninfected intramucosal SRCCs may be less likely to develop into advanced DGCs.

Genetic analysis of a case of Helicobacter pylori-uninfected intramucosal gastric cancer in a family with hereditary diffuse gastric cancer.

Germline mutations in CDH1, encoding E-cadherin, are known to be the causative mechanism of hereditary diffuse gastric cancer (HDGC). We encountered two cases of gastric cancer in a Japanese family with HDGC. A 28-year-old man (Case 1) died of advanced gastric cancer. His younger sister aged 27 (Case 2) was diagnosed with intramucosal signet ring cell carcinoma (SRCC). Both had identical germline CDH1 mutations, but Case 1 was positive for Helicobacter pylori infection, whereas Case 2 was negative. Case 2 underwent total gastrectomy. Whole-exome sequencing of an intramucosal SRCC in Case 2 revealed seven somatic mutations including one in CDH1. The six non-CDH1 mutations were classified as non-driver mutations. Decreased expression of E-cadherin in intramucosal SRCC was confirmed by immunohistochemistry. Our report demonstrated that CDH1 mutation was the only active driver mutation in Helicobacter pylori-uninfected intramucosal SRCC.

[Evaluation of the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years].

Endoscopic treatments, including endoscopic mucosal resection or endoscopic submucosal dissection, are well accepted as standard treatments for early gastric cancers. However, there are few studies evaluating the safety and efficacy of this approach for early gastric cancers in patients aged over 80 years, and the post-treatment prognosis remains unclear. Here, we retrospectively analyzed the medical records and evaluated the safety and efficacy of endoscopic treatment for early gastric cancers in patients aged over 80 years (group A) compared with non-elderly patients aged 65-79 years (group B) and under 65 years (group C). In this study, we enrolled 53 patients (mean age, 82 years) in group A, 217 patients (mean age, 73 years) in group B, and 89 patients (mean age, 60 years) in group C who received endoscopic treatment at Kyoto University Hospital between 2001 and 2010. The incidence of treatment-related complications including aspiration pneumonia, bleeding, and perforation was 19% (10/53) in group A, 9.7% (21/217) in group B, and 6.7% (6/89) in group C, respectively. In particular, only the incidence of aspiration pneumonia was significantly higher in group A [11% (6/53) ] than in the other two groups [1.8% (4/217) in group B and 1.1% (1/89) in group C]. There was no significant difference in the curative resection rate and recurrence rate including metachronous lesions among the three groups. In group A, the median survival calculated using the Kaplan-Meier method was 8.0 years, and the 5-year survival rate was 73%. No gastric cancer-related deaths were observed in all groups. In conclusion, endoscopic treatment for early gastric cancers may contribute to an improvement in life expectancy, even among patients aged over 80 years, provided an experienced gastroenterologist selects the appropriate patients based on not only the endoscopic findings for the lesion but also the severity of any comorbidities. However, it is noteworthy that our elderly group aged over 80 years had a high risk of developing aspiration pneumonia.

Instability of IGF-IGFBP complex as a cause of the different performance of serum and EDTA-plasma after storage: EDTA-plasma is preferable for evaluating bioactive IGF especially in the mouse.

OBJECTIVE: The insulin-like growth factor (IGF) signaling pathway is recognized as a potential target for treating several cancers, and strategies targeting the IGF type 1 receptor (IGF-1R) have been evaluated in many clinical trials. These suggested that the pretreatment level of circulating free IGF gives an estimate of IGF bioactivity and might be a predictive biomarker of the response to anti-IGF-1R antibodies. However, there is no defined protocol for measuring free and bioactive IGF concentrations, partly because the measurement procedures, including sample collection and handling, have not been standardized. We investigated the effects of sample collection methods and storage conditions on bioactive IGF measurement using a modified kinase receptor activation (KIRA) assay in human and mouse samples. DESIGN: Blood samples were obtained from healthy men and women, and from healthy male and female wild-type BALB/c mice. Serum and ethylenediaminetetraacetic acid (EDTA)-plasma samples were collected and used immediately or stored in small quantities at 4 °C or -80 °C for 3, 7, or 14 days. A bioassay directed against the phosphorylated IGF-1R using western blot analysis was developed as a modification of the KIRA assay, in which the level of phosphorylation of IGF-1R represented the IGF bioactivity in blood samples. RESULTS: The levels of bioactive IGFs in mouse serum stored at 4 °C increased markedly in a time-dependent manner; the increase was slightly reduced in samples stored at -80 °C. Analysis of mouse EDTA-plasma stored at 4 °C showed a similar pattern, but the time-dependent increase was less than in the serum samples. By contrast, the levels of bioactive IGFs in EDTA-plasma stored at -80 °C were stable over 14 days. The levels of human bioactive IGFs in both serum and EDTA-plasma stored at 4 °C increased slightly with time, but the increases were much smaller than in mouse samples. The levels of human bioactive IGF in both serum and EDTA-plasma stored at -80 °C were stable over 14 days. CONCLUSIONS: The use of EDTA-plasma avoids the problems with long-term storage. Therefore, EDTA-plasma should be used when measuring circulating IGF bioactivity, especially in mouse samples. All samples should be stored at -80 °C when long-term storage is unavoidable. Because of the large difference in the stability of the IGF-IGF-binding protein complex between the human and mouse in vitro, all samples should be handled carefully to ensure the accurate evaluation of IGF bioactivity, especially in mouse samples.

Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia.

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome characterized by persistent, severe hypoglycemia with a wide variety of solid tumors. It is considered to cause hypoglycemia by increasing the insulin-like bioactivity of the circulating insulin-like growth factor (IGF) system, however, the precise mechanism of hypoglycemia remains unclear. In this manuscript, we report on a patient suffering from NICTH caused by a small cell carcinoma of the colon. This is the first report focusing on the role of bioactive IGFs for this pathological condition. First, we demonstrated that the IGF signal pathway has been activated in this tumor in an autocrine and/or paracrine manner using immunohistochemical analysis. Second, we confirmed that bioactive IGFs in the patient's serum were increased using a modified kinase receptor activation assay, thus bioactive IGFs (mainly IGF-2) could be considered to play a major pathogenic role in enhanced hypoglycemic insulin-like activity. Third, increased IGF bioactivity in the patient's serum was completely inhibited by an anti-IGF neutralizing antibody in vitro. These results suggest that neutralization of bioactive IGFs might become a novel therapeutic strategy for NICTH to relieve the hypoglycemic symptoms together with the tumor suppressive effect.

Endoscopic band ligation for colonic diverticular hemorrhage.

BACKGROUND: The number of sample cases of colonic diverticular hemorrhage treated with endoscopic band ligation (EBL) has been small to date. OBJECTIVE: To elucidate the safety and efficacy of EBL for colonic diverticular hemorrhage. DESIGN: Retrospective study. SETTING: General hospital. PATIENTS: A total of 29 patients with 31 colonic diverticula with stigmata of recent hemorrhage (SRH). INTERVENTIONS: Urgent colonoscopy was performed after bowel preparation. When diverticula with SRH were identified, marking with hemoclips was done near the diverticula. The endoscope was removed and reinserted after a band-ligator device was attached to the tip of endoscope. At first, EBL was attempted. In patients who could not be treated with EBL, epinephrine injection or endoscopic clipping was performed. MAIN OUTCOME MEASUREMENTS: Procedure time, rate of hemostasis and rebleeding, complications. RESULTS: The mean procedure time was 47 ± 19 minutes. EBL was successfully completed in 27 colonic diverticula (87%); except in 3 diverticula with a small orifice and large dome and 1 diverticula in which the orifice was too large. Early rebleeding after EBL occurred in 3 of 27 cases (11%). Although 2 cases of sigmoid rebleeding could be managed by repeat EBL or conservatively, right hemicolectomy was performed in 1 ascending diverticulum, in which the bleeding source was not identified on repeat colonoscopy. Scar formation at previously banded diverticula was identified in 7 of 11 patients who underwent follow-up colonoscopy. There were no complications after EBL in any of the patients. LIMITATIONS: Retrospective study. CONCLUSIONS: EBL is a safe and effective treatment for colonic diverticular hemorrhage, and colonic diverticula resolve after EBL.

Enodoscopic band ligation (EBL) is superior to endoscopic clipping for the treatment of colonic diverticular hemorrhage.

BACKGROUND: Recently, endoscopic band ligation (EBL) has been used to treat colonic diverticular hemorrhage, but the number of EBL cases treated to date has been limited. This study aimed to evaluate the clinical outcomes of EBL in the treatment of colonic diverticular hemorrhage compared with those of endoclips. METHODS: At St. Luke's International Hospital in Tokyo, 66 patients were treated with EBL or endoclips from January 2004 to October 2010. Early rebleeding was defined as clinical evidence of recurrent bleeding within 30 days after initial treatment. Patients' demographics, rate of early rebleeding, and complications were retrospectively evaluated. RESULTS: Of the 66 patients, 18 were treated with EBL. The initial success rate for hemostasis with EBL was 100% with no complications. Early rebleeding was observed in one patient (6%), for whom eversion of a bleeding diverticulum in the sigmoid colon could not be obtained and early loss of the O-band occurred. However, the patient could be retreated with EBL. On the other hand, complete eversion could be obtained for all 10 patients with right-sided diverticula, and no early rebleeding occurred. Endoclips were used to treat 48 patients. Although the initial success rate for hemostasis was 100% without any complications, the rate of early rebleeding was 33% (16 patients), which was significantly higher than the rate for the EBL-treated group (P = 0.018). CONCLUSIONS: According to the findings, EBL should be considered safe, effective, and superior to endoclips for the treatment of colonic diverticular hemorrhage. The EBL procedure should be attempted as the initial therapy especially for the right-sided disease.

Endoscopic band ligation with a water-jet scope for the treatment of colonic diverticular hemorrhage.

Although lower gastrointestinal bleeding generally has a less severe course and stops spontaneously in most cases without therapeutic intervention, some patients require endoscopic, surgical, or angiographic treatment depending on the nature of the bleeding. We applied endoscopic band ligation (EBL) with a water-jet scope to bleeding colonic diverticula and evaluated the efficacy and safety of EBL retrospectively. Five consecutive patients were diagnosed as having colonic diverticular hemorrhage, and were treated with EBL at St Luke's International Hospital in Tokyo from June 2009 to August 2009. Comorbid diseases, usage of anti-platelet agents, hemoglobin level on admission, procedural time, complications such as perforation and abscess formation, and rebleeding after EBL were retrospectively evaluated. In all cases, EBL achieved successful immediate hemostasis without any procedural complications. In four of five cases, bleeding colonic diverticula were everted after EBL. The mean length of hospital stay after EBL was 5 days (range 4-8 days). No patient exhibited clinical evidence of further bleeding during the mean follow-up period of 3 months (range 2-4 months), and no further intervention was needed after EBL. EBL with a water-jet scope is considered to be a safe and effective endoscopic treatment for colonic diverticular hemorrhage.

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for superficial esophageal neoplasia. Is it safe for elderly patients?

BACKGROUND: Safety and efficacy of endoscopic submucosal dissection (ESD) for esophageal neoplasias have not been adequately investigated in elderly patients. This study was designed to evaluate the safety and efficacy of ESD for esophageal neoplasias in elderly patients. METHODS: Fifty-three superficial esophageal neoplasias treated with ESD using a combination of small-caliber-tip transparent hood and flex knife from May 2006 to June 2009 were divided into elderly group (aged 70 years or older: 25 lesions in 23 patients) and nonelderly group (younger than aged 70 years: 28 lesions in 25 patients). Therapeutic efficacy, complications, and follow-up results were evaluated retrospectively. RESULTS: The history of cerebral infarction or cardiopulmonary disease and the usage of antiplatelet agents or anticoagulants were significantly higher in elderly group (p 0.0050 and p 0.0013, respectively). Median procedural times in the elderly group and the nonelderly group were 93 ± 53 (range, 42-235) min and 95 ± 55 (range, 40-230) min (p 0.73), respectively. Median sizes of the neoplasias and the resected specimens were 14 ± 11 (range, 5-45) mm and 15 ± 17 (range, 5-83) mm (p 0.56), and 35 ± 12 (range, 18-60) mm and 38 ± 17 (range, 18-90) mm (p 0.38), respectively. En bloc resection rate was 100% in each group. Body temperature and white blood cell counts of the next day after ESD were significantly higher in the nonelderly group than in the elderly group (p 0.0087 and p 0.0043, respectively). There were no complications, such as postoperative bleeding or perforation, in each group. The median follow-up period of 23 ± 10 (range, 4-35) months in the elderly group revealed no local or distant metastasis. CONCLUSIONS: ESD with a combination of small-caliber-tip transparent hood and flex knife is a safe and effective treatment for superficial esophageal neoplasia in elderly and nonelderly patients.

Endoscopic submucosal dissection with a combination of small-caliber-tip transparent hood and flex knife for large superficial colorectal neoplasias including ileocecal lesions.

BACKGROUND: Large superficial neoplasias of the ileocecal region pose an increased degree of complexity for endoscopic resection. This study aimed to evaluate the safety and efficacy of endoscopic submucosal dissection (ESD) for large superficial colorectal neoplasias including ileocecal lesions. METHODS: A total of 33 superficial colorectal neoplasias, including eight neoplasias in the ileocecal region, were treated with ESD from December 2005 to April 2009. Therapeutic efficacy, complications, and follow-up results were retrospectively evaluated among three groups: ileocecal region, colon, and rectum. RESULTS: The mean size of all resected neoplasias was 35 +/- 15 mm (range, 20-80 mm) and that of all resected specimens was 41 +/- 15 mm (range, 23-82 mm). The mean procedural time was 121 +/- 90 min (range, 22-420 min). The difference in mean values among the three groups was not significant. The overall rate of en bloc resection was 91% (30/33). Histopathologically, both the lateral and vertical margins in the specimens resected en bloc tested negative (30/30). The rate for en bloc resection in the ileocecal region did not differ significantly from that for the other two groups (p = 0.20 compared with the rate for the colon and p = 0.12 compared with the rate for the rectum). Complications such as perforation and postoperative bleeding did not occur in the ileocecal group. No recurrence was observed in any cases during the mean follow-up period of 20 +/- 12 months (range, 4-44 months). CONCLUSIONS: The ESD approach is safe and effective for treating large superficial neoplasias of the ileocecal region such as other colorectal neoplasias.