Factors Related to Difficulty in Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is technically challenging, and research on predictive factors related to the difficulty in the procedure is limited. This study aimed to investigate the factors predicting the difficulty in esophageal ESD. METHODS: This retrospective study analyzed 303 lesions treated at our institution between April 2005 and June 2021. The following 13 factors were evaluated: sex, age, tumor location, tumor localization, macroscopic type, tumor size, tumor circumference, preoperative diagnosis of histological type, preoperative diagnosis of invasion depth, previous radiotherapy for esophageal cancer, metachronous lesion located close to post-ESD scar, operator's skill, and use of a clip-and-thread traction method. Difficult esophageal ESD cases were defined as those requiring long procedure time (>120 min). RESULTS: Fifty-one lesions (16.8%) met the defined criterion for difficult cases of esophageal ESD. Logistic regression analysis identified tumor size larger than 30 mm (odds ratio: 9.17, 95% confidence interval: 4.27-19.69, p < 0.001) and tumor circumference more than half that of the esophagus (odds ratio 2.53, 95% confidence interval: 1.15-5.54, p = 0.021) as independent predictive factors related to difficulty in esophageal ESD. CONCLUSION: Tumor size larger than 30 mm and tumor circumference more than half that of the esophagus can predict difficulty in performing esophageal ESD. This knowledge can provide useful information for developing ESD strategies and selecting a suitable operator on a case-by-case basis to achieve favorable clinical outcomes.

Usefulness of magnifying endoscopy with acetic acid and narrow-band imaging for the diagnosis of duodenal neoplasms: proposal of a diagnostic algorithm.

BACKGROUND: This study aimed to clarify the features of superficial non-ampullary duodenal epithelial tumors (SNADETs) on magnifying endoscopy with narrow-band imaging (M-NBI) and magnifying endoscopy with acetic acid and narrow-band imaging (M-AANBI), and evaluate the efficacy of M-NBI/M-AANBI to distinguish high-grade adenomas or adenocarcinomas (HGA/AC) from low-grade adenomas (LGA). METHODS: Clinicopathological data on 62 SNADETs in 58 patients who underwent preoperative M-NBI/M-AANBI and endoscopic resection were retrospectively reviewed. The pathological results were classified into two categories, LGA and HGA/AC. We evaluated microvascular patterns (MVPs) and microsurface patterns (MSPs) observed by M-NBI and MSPs observed by M-AANBI for characterizing LGA and HGA/AC. The kappa value was calculated to assess the interobserver and intraobserver agreements of evaluation of M-AANBI images. RESULTS: Pathologically, 38 lesions (61.3%) were LGA and 24 lesions (38.7%) were HGA/AC. HGA/AC tended to have irregular MVP and/or MSP on M-NBI. M-NBI diagnostic performance to distinguish HGA/AC from LGA showed 62.5% sensitivity, 68.4% specificity, and 66.1% accuracy. SNADETs had irregular MSP on M-AANBI. Three irregularity grades (iG) of MSP were observed by M-AANBI as follows: iG1, mild; iG2, moderate; iG3, significant. HGA/AC lesions had a significantly higher rate of iG3 than LGA lesions (p < 0.001). The iG2 was associated with HGA/AC in elevated lesions and LGA in depressed lesions. The diagnostic performance of M-AANBI was as follows: 95.8% sensitivity, 97.4% specificity, and 96.8% accuracy. The diagnostic accuracy of M-AANBI was significantly higher than that of M-NBI (p < 0.001). The kappa value for interobserver agreement on the diagnosis and irregularity grading of M-AANBI images was 0.742 and 0.719, respectively. These data indicate substantial interobserver agreement. Based on the above-mentioned results, we developed a M-AANBI diagnostic algorithm for SNADETs. CONCLUSION: The diagnostic algorithm for SNADETs using M-AANBI may be useful for differentiating between LGA and HGA/AC.

Clinical utility of endoscopic submucosal dissection using the pocket-creation method with a HookKnife and preoperative evaluation by endoscopic ultrasonography for the treatment of rectal neuroendocrine tumors.

BACKGROUND: Various endoscopic methods have been developed to remove small rectal neuroendocrine tumors (NETs). This study aimed to evaluate the clinical utility of endoscopic submucosal dissection using the pocket-creation method (ESD-PCM) with a HookKnife, following preoperative evaluation by endoscopic ultrasonography (EUS), for the treatment of rectal NETs. METHODS: We analyzed retrospectively consecutive patients who underwent ESD-PCM with a HookKnife for the removal of rectal NETs, with a size less than 10 mm, at Mie University Hospital between June 2015 and December 2019. All the rectal NETs were resected by ESD-PCM with a HookKnife. The R0 resection rate, procedure time, adverse event rate, diagnostic accuracy of tumor size and invasion depth evaluated by preoperative EUS, and follow-up outcome were evaluated retrospectively. RESULTS: The study group comprised 12 patients with 12 resected lesions. The median tumor size of the resected specimens was 5 mm and the size and invasion depth of each tumor was approximately equal to that predicted by preoperative EUS. R0 resection was achieved in all cases, without adverse events. The median procedure time was 50.5 min, which did not differ from previous studies. No recurrence was observed during the median follow-up period of 34.4 months (range, 5.2-60.0 months). CONCLUSIONS: ESD-PCM with a HookKnife provides a favorable clinical utility for removing rectal NETs, with high R0 resection rate and good follow-up outcome. In addition, EUS is useful for evaluating preoperatively the size and invasion depth of rectal NETs.

Utility of the narrow-band imaging international colorectal endoscopic classification for optical diagnosis of colorectal polyp histology in clinical practice: a retrospective study.

BACKGROUND: Narrow-band imaging (NBI) highlights the surface structures and vessels of colorectal polyps and is useful for determining the polyp histology. The narrow-band imaging international colorectal endoscopic (NICE) classification is a diagnostic tool for determining colorectal polyp histology based on NBI without optical magnification. In this study, we aimed to investigate the value of each type of the NICE classification for determining colorectal polyp histology using endoscopy data accumulated in a clinical setting. METHODS: Endoscopy data for 534 colorectal polyps (316 patients) treated at our facility were retrospectively analyzed. First, we investigated the diagnostic performance of each type of the NICE classification for the optical diagnosis of colorectal polyp histology. The procedures were performed by experienced endoscopists using high-definition colonoscopy without optical magnification. Second, inter-observer and intra-observer agreements were assessed after providing experts and non-experts with a short lecture on the NICE classification. Using 50 fine NBI images of colorectal polyps without optical magnification, the inter-observer and intra-observer agreements between five experts and five non-experts were assessed. RESULTS: The sensitivity, specificity, and accuracy values were 86.0%, 99.6%, and 98.5% for NICE type 1 lesions; 99.2%, 85.2%, and 97.8% for NICE type 2 lesions; and 81.8%, 99.6%, and 99.3% for NICE type 3 lesions, respectively. The inter-observer and intra-observer agreements ranged from substantial to excellent for both experts and non-experts. CONCLUSIONS: The NICE classification had good diagnostic ability in terms of determining the polyp histology and demonstrated a high level of reproducibility among experts and non-experts. Thus, the NICE classification is a useful clinical tool that can be used without optical magnification.

Protein S Exacerbates Chronic Liver Injury and Fibrosis.

Protein S is a vitamin K-dependent glycoprotein produced mainly in the liver with anticoagulant, anti-inflammatory, immune-modulatory, and antiapoptotic properties. Protein S exacerbates acute liver injury by prolonging the survival of liver immune cells. However, the effect of protein S on chronic liver injury and fibrosis is unknown. Here, we investigated whether human protein S can affect chronic liver injury and fibrosis. Liver injury/fibrosis was induced by carbon tetrachloride injection in mice overexpressing human protein S and in wild-type mice. Human protein S transgenic mice receiving carbon tetrachloride showed significantly higher circulating levels of liver transaminases, increased liver expression of inflammatory cytokines, significantly more extended liver fibrosis, and areas with DNA breakage after chronic injury compared with wild-type mice. Wild-type mice infused with exogenous human protein S exhibited exacerbated liver injury and increased number of hepatic stellate cells compared with untreated mice. Human protein S inhibited apoptosis and increased Akt pathway activation in hepatic stellate cells. The antiapoptotic activity of protein S may play a role in chronic liver injury and subsequent liver fibrosis.

Development of a sensitive immunochromatographic kit using fluorescent silica nanoparticles for rapid serodiagnosis of amebiasis.

We have previously shown that the C-terminal region of the intermediate subunit of Entamoeba histolytica galactose- and N-acetyl-D-galactosamine-inhibitable lectin (C-Igl) is a useful antigen for serodiagnosis of amebiasis. An immunochromatographic kit was developed using fluorescent silica nanoparticles coated with C-Igl prepared in Escherichia coli. Samples for examination were added to the freeze-dried particles and then applied to the immunochromatographic device, in which a test line on the membrane was also coated with C-Igl. Fluorescent intensity was measured using a hand-held reader. In an evaluation of the kit using a human monoclonal antibody, the minimum amount of C-Igl specific antibody showing positive results was 100 pg. In the evaluation of serum samples with different antibody titers in indirect immunofluorescent antibody tests in the kit, 20 µL of serum was sufficient to obtain positive results at 30 min. Serum samples from symptomatic patients with amebic colitis and amebic liver abscess and those from asymptomatic E. histolytica-cyst carriers showed positive results in the kit. Based on evaluation using sera from healthy controls and patients with other infectious diseases, the sensitivity and specificity of the kit were 100 and 97.6%, respectively. Therefore, we conclude that the newly developed kit is useful for rapid serodiagnosis of amebiasis.

Esophageal squamous cell neoplasia is an independent negative prognostic factor for head and neck cancer patients.

BACKGROUND: Patients with head and neck cancer (HNC) have a high incidence of esophageal squamous cell neoplasms (ESCN). ESCN also has a negative impact on the survival of HNC patients. However, recent endoscopic advances enable the early detection of ESCN, and novel treatments may lead to improving survival rates for HNC patients with ESCN. METHODS: HNC patients who underwent magnifying esophagogastroduodenoscopy (EGDS) from 2005 to 2012 were included in this study (n = 226). We analyzed the prevalence and prognostic value of ESCN in HNC patients and the difference in overall survival between HNC patients with and without ESCN. RESULTS: Thirty-four patients (15%) developed an ESCN during their clinical course. Of the 34 patients, 10 patients underwent endoscopic resection for ESCN and 10 patients underwent simultaneous chemoradiation therapy for HNC and ESCN. The 3-year survival rates in HNC patients with and without ESCN were 53% and 70%, respectively. Multivariate analysis identified the advanced clinical stage of the HNC [hazard ratio (HR) = 2.15; 95% confidence interval (CI) = 1.18-3.93; p = 0.012] and the presence of ESCN (HR = 1.73; 95% CI = 1.00-2.97; p = 0.049) as significant and independent determinants of overall survival. CONCLUSIONS: Our study suggests that although the survival of HNC patients with ESCN may be improved by routine EGDS during tumor surveys and by advances in endoscopy, the presence of ESCN still remains an independent negative prognostic factor for HNC patients.

18F-FDG uptake in the stomach on screening PET/CT: value for predicting Helicobacter pylori infection and chronic atrophic gastritis.

BACKGROUND: The aim of this study was to determine the value of 18F-FDG uptake on screening PET/CT images for the prediction of Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis. METHODS: Among subjects who underwent 18F-FDG PET/CT for cancer screening from April 2005 to November 2015, PET/CT images were analyzed in 88 subjects who had gastrointestinal fiberscopy within 6 months. The volumes of interest (VOIs) were placed in the fornix, corpus and antrum of the stomach to determine maximal standardized uptake value (SUVmax) and mean SUV (SUVmean). Receiver operating characteristic curve (ROC) analysis was performed to determine the diagnostic performance of SUV indicators in predicting H. pylori infection and chronic atrophic gastritis. RESULTS: SUV indicators of the stomach were significantly higher in subjects with H. pylori infection than those without (from P < 0.001 to P < 0.05). ROC analysis revealed that SUVmean had the highest performance in predicting H. pylori infection (AUC 0.807) and chronic atrophic gastritis (AUC 0.784). SUVmean exhibited the sensitivity of 86.5 % and the specificity of 70.6 % in predicting H. pylori infection, and the sensitivity of 75.0 % and 78.6 % in predicting chronic atrophic gastritis. CONCLUSION: Assessment of 18F-FDG uptake in the stomach reflecting active inflammation is useful in predicting patients with H. pylori infection and subsequent chronic atrophic gastritis which is closely associated with the risk of gastric neoplasms.

Endoscopic findings and lesion distribution in amebic colitis.

A retrospective cohort study was conducted in 55 symptomatic patients with amebic colitis that visited at St. Luke's International Hospital and Mie University Hospital from 1994 through 2013. To diagnose amebic colitis, 40 patients underwent total colonoscopy within 1 week after hospital visiting and before receiving any treatment. The percentage of characteristic endoscopic findings of amebic colitis including discrete ulcers or erosions with white or yellow exudates were 0% in terminal ileum, 93% in cecum, 28% in ascending, 25% in transverse, 15% in descending, 20% in sigmoid colon and 45% in rectum. The rectal lesions in 55% of patients with amebic colitis were nonspecific. The trophozoite identification rate by direct smear of intestinal tract washings performed during colonoscopy was 88%. The protozoan identification rate was 70% in biopsy specimens taken from the periphery of the characteristic discrete ulcers. Total colonoscopy should be considered for the diagnosis of amebic colitis.

Endoscopic submucosal dissection for superficial esophageal cancer in a diverticulum: A case report with literature review.

Superficial esophageal cancer (SEC) in a diverticulum is rare and has a high risk of perforation during endoscopic resection. Although endoscopic submucosal dissection (ESD) is a standard treatment option, it is challenging to perform. Here, we describe the case of a 79-year-old male patient with a history of ESD for SEC. Surveillance esophagogastroduodenoscopy identified a 20-mm-sized reddish depressed lesion in a diverticulum in the middle esophagus. The lesion was confirmed to be squamous cell carcinoma by biopsy. Magnification endoscopy with narrow-band imaging showed intraepithelial papillary capillary loops of type B1 according to the magnified endoscopic classification of the Japan Esophageal Society. Endoscopic ultrasonography revealed the presence of the muscular layer of the esophagus wall in the diverticulum. Therefore, the lesion was diagnosed as SEC, confined to the epithelium or lamina propria mucosae, in a Rokitansky diverticulum. Based on these findings, ESD was considered technically feasible. Traction-assisted ESD using clip with line was performed, and en bloc resection was achieved without adverse events. The resected specimen pathologically revealed a squamous cell carcinoma confined to the lamina propria mucosae without lymphovascular invasion, suggesting a curative resection. The patient recovered well, and no recurrence has been observed for 5 years after the ESD. Whether ESD is appropriate for the treatment of SEC in a diverticulum remains unclear. However, our case shows that it can be a treatment option in such cases due to its minimal invasiveness and good effectiveness.

The efficacy of rebamipide add-on therapy in arthritic patients with COX-2 selective inhibitor-related gastrointestinal events: a prospective, randomized, open-label blinded-endpoint pilot study by the GLORIA study group.

OBJECTIVE: We aimed to confirm the effect of combined treatment with celecoxib and rebamipide would be more effective than celecoxib alone for prevention of upper gastrointestinal (GI) events. METHODS: Patients with rheumatoid arthritis, osteoarthritis, and low back pain were enrolled in this study. Patients were randomized to two groups: a monotherapy group (100 mg celecoxib twice daily) and a combination therapy group (add on 100 mg of rebamipide three times a day). The GI mucosal injury was evaluated by endoscopic examination before treatment and at 3 months. The primary endpoint was to evaluate the preventive effect of the combination therapy group for GI events, endoscopic upper GI ulcers and intolerable GI symptoms, compared with the monotherapy group. RESULTS: Seventy-five patients were enrolled. Sixty-five patients were analyzed (16 males, 49 females; mean age: 67 ± 13 years). The prevalence of upper GI events, five of endoscopic GI ulcers and one of intolerable GI symptoms, were 6/34 (17.6%) in the monotherapy group and 0/31 in the combination therapy group, p = 0.0252. CONCLUSIONS: The combination therapy group was more effective than the monotherapy group for prevention of upper GI events in this study. Rebamipide might be a candidate for an option to prevent COX-2 selective inhibitor-induced upper GI events.

Invasive Colon Cancer Inadvertently Resected by Cold Snare Polypectomy.

A 74-year-old man with anemia underwent colonoscopy, which revealed a 4-mm polyp in the ascending colon. The polyp was subsequently diagnosed as an adenomatous lesion according to the narrow-band imaging (NBI) International Colorectal Endoscopic classification/Japan NBI Expert Team classification and resected via cold snare polypectomy (CSP). However, a pathological examination revealed a well-differentiated adenocarcinoma with a positive vertical margin. We performed additional endoscopic resection at the CSP scar area, revealing residual submucosal cancer with lymphatic involvement. The patient then underwent additional surgical resection. In such cases, additional endoscopic resection might be a treatment option.

Risk Factors Associated with Painful Colonoscopy and Prolonged Cecal Intubation Time in Female Patients.

Objectives: Few studies have examined risk factors leading to painful colonoscopy and prolonged cecal intubation time in female patients. We aimed to determine the factors associated with painful colonoscopy and prolonged cecal intubation time in female patients. Methods: This retrospective study analyzed prospectively collected data from a randomized controlled trial with female patients who underwent colonoscopy. Multivariate logistic and linear regression analyses were performed using the following factors that might be associated with painful colonoscopy and prolonged cecal intubation time, respectively: age, body mass index, history of colonoscopy, previous abdominal surgery, routine use of laxatives, inadequate bowel preparation, sigmoid colon diverticulosis, use of a small-caliber colonoscope, and an inexperienced operator. Results: The study enrolled 219 female patients aged >20 years. Using the receiver operating characteristic curve, painful colonoscopy was defined in cases where the visual analogue scale of overall pain was ≥50 mm. Logistic regression analysis for risk factors associated with painful colonoscopy revealed that sigmoid colon diverticulosis [odds ratio (OR), 2.496; 95% confidence interval (CI), 1.013-5.646; p=0.028] was a risk factor for painful colonoscopy; conversely, the use of a small-caliber colonoscope was a negative factor for painful colonoscopy (OR, 0.436; 95% CI, 0.214-0.889, p=0.022). In linear regression analysis, inadequate bowel preparation was significantly associated with prolonged cecal intubation time (ß-coefficient, 3.583; 95% confidence interval, 0.578-6.588; p=0.020). Conclusions: Female patients with sigmoid colon diverticulosis are more likely to experience severe pain during colonoscopy, and those with inadequate bowel preparation may require more time for cecal intubation.