Safety and Efficacy of Cold Snare Polypectomy Without Submucosal Injection for Large Sessile Serrated Lesions: A Prospective Study.

BACKGROUND & AIMS: Cold snare polypectomy (CSP) has become the standard resection method for small colorectal polyps (<10 mm). Sessile serrated lesions (SSL) have low prevalence of advanced histology irrespective of size, and thus could be amenable to CSP. In this study, we evaluated the safety and efficacy of CSP for SSLs ≥10 mm. METHODS: Between November 2018 and January 2020, we prospectively enrolled 300 consecutive patients who underwent CSP for 474 SSLs ≥10 mm. To delineate SSL borders, indigo carmine chromoendoscopy and/or image-enhanced endoscopy was conducted. Piecemeal CSP (pCSP) was performed in cases where en-bloc resection was difficult. Biopsy specimens were obtained from the margins of the post-polypectomy defect to confirm complete resection. Surveillance colonoscopy was performed to screen for local recurrence. RESULTS: All lesions were successfully resected using CSP without submucosal injection. The median diameter of the resected lesions was 14 mm, and pCSP was used to resect 106 (22%) lesions. Post-polypectomy biopsies revealed residual serrated tissue in only one case (0.2%). Adverse events included immediate bleeding in 8 (3%) patients; no delayed bleeding events occurred, irrespective of the use of antithrombotic drugs. During a 7-month median follow-up period, surveillance colonoscopies were performed for 384 lesions (81%), and no local recurrences were detected. CONCLUSIONS: CSP without submucosal injection is a safe and effective treatment for SSLs ≥10 mm. UMIN Clinical Trials, Number: UMIN000034763.

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats.

NEW FINDINGS: What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres by upregulating peroxisome proliferator-activated receptor-γ coactivator-1α and activating the calcineurin-nuclear factor of activated T-cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse. ABSTRACT: Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7 days before hindlimb unloading (HU) for 2 weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured. Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.

A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models.

PURPOSE: The clinical application of gemcitabine (GEM) is limited by its pharmacokinetic properties. The aim of this study was to characterize the stability in circulating plasma, tumor targeting, and payload release of liposome-encapsulated GEM, FF-10832. METHODS: Antitumor activity was assessed in xenograft mouse models of human pancreatic cancer. The pharmacokinetics of GEM and its active metabolite dFdCTP were also evaluated. RESULTS: In mice with Capan-1 tumors, the dose-normalized areas under the curve (AUCs) after FF-10832 administration in plasma and tumor were 672 and 1047 times higher, respectively, than after using unencapsulated GEM. The tumor-to-bone marrow AUC ratio of dFdCTP was approximately eight times higher after FF-10832 administration than after GEM administration. These results indicated that liposomal encapsulation produced long-term stability in circulating plasma and tumor-selective targeting of GEM. In mice with Capan-1, SUIT-2, and BxPC-3 tumors, FF-10832 had better antitumor activity and tolerability than GEM. Internalization of FF-10832 in tumor-associated macrophages (TAMs) was revealed by flow cytometry and confocal laser scanning microscopy, and GEM was efficiently released from isolated macrophages of mice treated with FF-10832. These results suggest that TAMs are one of the potential reservoirs of GEM in tumors. CONCLUSION: This study found that FF-10832 had favorable pharmacokinetic properties. The liposomal formulation was more effective and tolerable than unencapsulated GEM in mouse xenograft tumor models. Hence, FF-10832 is a promising candidate for the treatment of pancreatic cancer.

A new classification for the diagnosis of superficial non-ampullary duodenal epithelial tumors using endocytoscopy: A prospective study.

BACKGROUND AND AIM: Although the frequency of endoscopic diagnosis of superficial non-ampullary duodenal epithelial tumors (SNADETs) has been increasing in recent years, no criteria for the endoscopic diagnosis of these tumors have been established yet. The aim of this study was to assess the usefulness of endocytoscopy for diagnosis SNADETs and to establish new criteria. METHODS: This prospective study was conducted at the NTT Medical Center Tokyo from May 2019 to July 2020, and a total of 100 consecutive SNADETs were enrolled. All the endocytoscopic images of the lesions and surrounding normal mucosa were classified into three groups according to the degree of structural atypia and the nuclear morphology and size. The endocytoscopic diagnoses using endocytoscopic classification was compared with the final histopathological diagnoses. RESULTS: Data of 93 patients with 98 lesions were included in the analysis. The preoperative diagnosis by endocytoscopy coincided with the final histopathological diagnosis in 85 (86.7%) of 98 SNADETs. In addition, the sensitivity and specificity for VCL 4/5 were 87.7% and 85.4%, respectively. In contrast, the accuracy, sensitivity, and specificity of preoperative diagnosis by biopsy were 64.3%, 50.9%, and 82.9%, respectively. Preoperative diagnosis by endocytoscopy showed significantly superior accuracy and sensitivity as compared with preoperative biopsy diagnosis (P < 0.001, respectively). CONCLUSIONS: This new classification (endocytoscopic classification) allows prediction of the tumor histopathology in real time, during endocytoscopy without biopsy, and is expected to be of help in determining the appropriate therapeutic strategies for individual cases of SNADETs. (Clinical trial registration number: UMIN000038643.).

Risk factors of delayed bleeding after endoscopic resection of superficial non-ampullary duodenal epithelial tumors and prevention by over-the-scope and conventional clipping.

OBJECTIVES: This study was aimed to reveal risk factors for delayed bleeding after endoscopic resection (ER) of superficial non-ampullary duodenal epithelial tumors (SNADETs) and at exploring measures to prevent this complication. METHODS: A total of 235 consecutive patients with 249 SNADETs who had undergone ER were enrolled in this study. They were divided into two groups: OTSC group, consisting of the initial 114 cases in which the defects were closed only using OTSCs; and OTSC-c group, consisting of the later 135 cases in which conventional clips were additionally used to cover the inverted submucosa after post-procedure defect closure using OTSCs. The therapeutic outcomes were then compared between the OTSC and OTSC-c groups. RESULTS: All lesions were successfully resected en-bloc, and the R0 resection rate was 92.4%. The complete defect closure rate was 90.0% and no delayed perforation occurred when successful defect closure was achieved. The rate of delayed bleeding was significantly higher in the OTSC group than in OTSC-c group (11.4% vs. 1.5%, P = 0.001). Multivariate logistic regression analyses revealed that tumor location distal to the ampulla (OR 10.0; 95% CI 1.24-81.0, P = 0.03) and use of a DOAC (OR 8.83; 95% CI 1.13-68.7, P = 0.04) were significant independent predictors of delayed bleeding. Propensity score-matching analysis revealed that additional use of conventional clips was associated with a significantly reduced risk of delayed bleeding (P = 0.003). CONCLUSIONS: Additional use of conventional clips after prophylactic defect closure using OTSCs appears to be useful to reduce the risk of delayed bleeding after ER of SNADETs. UMIN Clinical Trials (No. 000035478).

Significance of the 7th postoperative day neutrophil-to-lymphocyte ratio in colorectal cancer.

PURPOSE: High neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and is associated with poor survival in localized or metastatic cancer. Preoperative NLR in colorectal cancer reportedly correlates with recurrence-free survival and is useful as a recurrence prediction factor. No reports have yet investigated recurrence factors using postoperative NLR. This study assessed the predictive value of NLR preoperatively and on the first (NLR1) and seventh day (NLR7) postoperatively in patients with stage II colorectal cancer. METHODS: We performed a retrospective cohort study involving patients undergoing colorectal resection at a single institution between January 2012 and December 2016; we used medical records of 176 consecutive patients with stage II colorectal cancer undergoing curative tumor resection. NLRs as well as clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with recurrence-free survival (RFS). RESULTS: Univariate analysis revealed that elevated NLR, NLR7, and lymphatic invasion were significantly associated with decreased RFS (p < 0.05). NLR7 was revealed as significant via multivariate analysis (p = 0.013). The 3-year RFS rate was 87.1% for patients with normal NLR7 and 70.3% for those with elevated NLR7. CONCLUSION: Elevated seventh-day postoperative NLR is a significant independent predictor of reduced RFS for patients with stage II colorectal cancer and may be a potential biomarker for identifying candidates for adjuvant chemotherapy.

Acute effects of lactic acid-fermented and enzyme-digested soybean on protein synthesis via mTOR signaling in the skeletal muscle.

Protein-containing nutrients result in the efficient hypertrophy of muscles by increasing muscle protein synthesis. Soybean is often ingested by athletes or individuals who exercise; however, it takes very long to be absorbed. Lactic acid-fermented and enzyme-digested (LFED) soybean is absorbed faster than untreated soybean. This study aims at determining muscle protein synthesis after ingesting a single bolus of soybean or LFED soybean produced by lactic acid bacteria and protease digestion. Eight-week-old overnight-fasted ICR mice were administered powdered or LFED soybean. Mice were euthanized at 7, 15, 30, 60, 90, and 120 min after soybean intake. We have demonstrated that LFED soybean administration was quicker in stimulating muscle protein synthesis by activating mammalian target of rapamycin (mTOR) signaling than orally ingesting untreated soybean in the gastrocnemius muscle. These results suggested that LFED soybean is a more efficient source of nutrition for muscle hypertrophy than untreated soybean.

G12V and G12C mutations in the gene KRAS are associated with a poorer prognosis in primary colorectal cancer.

PURPOSE: The increased incidence of colorectal cancer (CRC) has necessitated the development of novel prognostic and predictive factors from which new diagnostic tests could evolve. Evidence suggests the KRAS gene represents such a factor; its mutations are considered to be early indicators of CRC progression. This study assessed the prognostic impact of specific known KRAS codon 12/13 mutations on survival in patients with CRC. METHODS: Formalin-fixed paraffin-embedded tissue blocks or sections from primary were obtained from patients registered between 2014 and 2016 for genomic DNA extraction. KRAS gene was analyzed by direct sequencing or Luminex assay. The primary endpoint was the frequency of KRAS gene mutations and the secondary endpoints were differences in KRAS mutation rates by various stratification factors. Univariate and multivariate analyses were performed to investigate relationships between KRAS mutation rates and patient background factors. RESULTS: Sequencing of 200 CRC primary tumor samples demonstrated 74 (37.5%) with KRAS mutations in codons 12 (77%; 57/74) and 13 (23%; 17/74), all of which were TNM stages I-III. Tumors with KRAS mutations were more frequently located in the right side of the colon. Multivariate analysis indicated that G12V or G12C mutations were associated with poor prognosis [hazard ratio (HR) = 3.77, 95% confidence interval (CI), 1.54-8.39 and HR = 6.57; 95% CI, 1.90-17.7, respectively] in terms of recurrence-free survival. CONCLUSION: KRAS codon 12G-to-V or G-to-C mutations are independent prognostic factors in patients with stage I-III CRC.

Transcutaneous carbon dioxide attenuates impaired oxidative capacity in skeletal muscle in hyperglycemia model.

Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)-induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO2. STZ-induced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.

Isolation and characterization of rice cesium transporter genes from a rice-transporter-enriched yeast expression library.

A considerable portion of agricultural land in central-east Japan has been contaminated by radioactive material, particularly radioactive Cs, due to the industrial accident at the Fukushima Daiichi nuclear power plant. Understanding the mechanism of absorption, translocation and accumulation of Cs+ in plants will greatly assist in developing approaches to help reduce the radioactive contamination of agricultural products. At present, however, little is known regarding the Cs+ transporters in rice. A transporter-enriched yeast expression library was constructed and the library was screened for Cs+ transporter genes. The 1452 full length cDNAs encoding transporter genes were obtained from the Rice Genome Resource Center and 1358 clones of these transporter genes were successively subcloned into yeast expression vectors; which were then transferred into yeast. Using this library, both positive and negative selection screens can be performed, which have not been previously possible. The constructed library is an excellent tool for the isolation of novel transporter genes. This library was screened for clones that were sensitive to Cs+ using a SD-Gal medium containing either 30 or 70 mM CsCl; resulting in the isolation of 13 Cs+ sensitive clones. 137 Cs absorption experiments were conducted and confirmed that all of the identified clones were able to absorb 137 Cs. A total of 3 potassium transporters, 2 ABC transporters and 1 NRAMP transporter were among the 13 identified clones.

Gel immersion endoscopy: a novel method to secure the visual field during endoscopy in bleeding patients (with videos).

BACKGROUND AND AIMS: It is difficult to secure the visual field during endoscopy for GI bleeding or colonoscopy without preparation because the injected water is rapidly mixed with fresh blood or stool. We developed a novel method to secure the visual field in these situations. METHODS: Clear gel with the appropriate viscosity to prevent rapid mixing is injected through the accessory channel, instead of water. A vinyl tube was used as an in vitro GI bleeding model. After filling the lumen with indigo carmine dye, air insufflation and water injection are not effective for securing the visual field. However, after gel injection, the bleeding source is observed clearly in the space occupied by the gel. The efficacy of this method was evaluated subjectively in clinical use. From February 2014 until June 2015, gel immersion was used in 17 consecutive patients when the visual field could not be secured with routine insufflation. RESULTS: Of these 17 patients, gel injection was very effective in 10, effective in 5, slightly effective in 1, and not effective in 1. There were no adverse events associated with this method. CONCLUSION: Gel immersion endoscopy is safe and effective for securing the visual field, creating a space for endoscopic visualization and treatment in otherwise difficult situations.

Laparoscopy-assisted nonexposed endoscopic full-thickness resection for local resection after endoscopic submucosal dissection.

Video 1Nonexposed endoscopic wall inversion surgery for local resection of microscopic residual tumor after endoscopic submucosal dissection.

A case of small bowel aneurysm hemorrhage with submucosal tumor-like findings.

A 51-year-old woman visited our hospital with the chief complaint of tarry stools. Contrast-enhanced abdominal computed tomography revealed leakage of contrast medium into the lumen of the small intestine. Subsequently, a double-balloon endoscopy was performed, which revealed a submucosal mass-like lesion in the jejunum. Although hemostasis was attempted with clips, complete hemostasis was difficult to achieve, and angiographic embolization was performed. Nevertheless, the anemia progressed, and a small bowel resection was performed. Histopathological examination led to a diagnosis of a ruptured submucosal aneurysm of the small intestine. Endoscopic hemostasis is often difficult to achieve for submucosal aneurysms in the intestine. The submucosal tumor-like finding observed on endoscopy in submucosal aneurysms is termed an "SMT-like sign" and is considered an important finding to diagnose aneurysms.

A case of anal canal carcinoma with pagetoid spread that was curatively resected by multiple endoscopic and surgical treatments.

A 57-year-old woman with no significant medical history was referred after a colonoscopy for abdominal distension, which revealed a tumor in the lower rectum. Pre-operative colonoscopy showed the tumor was 12 mm in size, located from the anorectal junction to beyond the dentate line, and was diagnosed as high-grade intramucosal neoplasia or shallow submucosal invasive cancer. Endoscopic submucosal dissection was performed, and the lesion was resected en bloc. Pathological examination revealed moderately differentiated tubular adenocarcinoma with tubulovillous adenoma. The stratified squamous epithelium adjacent to the anal side of the lesion showed pagetoid spread of atypical cells with positive horizontal margins. We referred her to a surgeon for radical treatment. The mucosa surrounding the endoscopic submucosal dissection scar was normal on narrow-band imaging magnification. We marked its oral side endoscopically as the resected boundary. Transanal local excision was performed. The horizontal margins were positive because atypical cells had spread into the stratified squamous epithelium of the anorectal side of the lesion. The patient was followed on an outpatient basis. Sixty days postoperatively, residual tumor growth was observed. The second local resection was performed after mapping biopsy. All resection margins were negative, there was no lymphovascular invasion. One year after surgery, no recurrence was observed. Regarding endoscopic findings, there are no reports of endoscopic findings of the rectal mucosa, or the squamous epithelium of the anus of pagetoid spread. Here, we report a review of perianal Paget's Disease that resulted in difficulties in borderline diagnosis of pagetoid spread, resulting in multiple therapeutic interventions.

Comparison of cold snare polypectomy for sessile serrated lesions ≥10 mm between experienced and trainee endoscopists: A propensity score matching cohort study.

Objectives: Previous studies of cold snare polypectomy (CSP) for sessile serrated lesions (SSLs) ≥10 mm were performed by experienced endoscopists, and therefore their skills might have significantly influenced results. In this study, we compared the efficacy and safety of CSP for SSLs ≥10 mm between experienced and trainee endoscopists. Methods: In a 1:1 propensity score matched retrospective cohort study, we compared the complete resection rate, en-bloc resection rate, adverse event rate, and procedure time between experienced and trainee groups. Thirteen endoscopists performed CSP, and we defined the experienced group as endoscopists with board certification from the Japan Gastroenterological Endoscopy Society. Results: We examined 616 lesions with SSLs ≥10 mm resected by CSP between February 2018 and May 2022. We excluded 61 lesions from the analysis because they had simultaneously undergone hot snare polypectomy (n = 57) or had been taken over by experienced endoscopists from trainees in the CSP procedure (n = 4). Finally, we identified 217 propensity score-matched pairs (n = 434). Between experienced and trainee groups, the results were complete resection rate (100 vs. 100%; p = 1.00), en-bloc resection rate (73.2 vs. 75.6%; p = 0.24), adverse event rate (3.2 vs. 2.8%; p = 0.77), or procedure time (6.2 vs. 5.9 min; p = 0.64). Conclusions: We have demonstrated the safety and efficacy of CSP for SSLs ≥10 mm performed by experienced and trainee endoscopists.

Endoscopic management of gastric ectopic pancreas with repeated ulcerations and bleeding: A case report.

A 25-year-old man was referred to our center for investigation of a gastric submucosal tumor and an ulcer that had developed on its oral side. Endoscopic ultrasonography findings suggested the presence of an ectopic pancreas, and treatment with an oral proton pump inhibitor was planned for the ulcer. Over the subsequent 3 years, the patient endured recurring epigastric pain and episodes of passing black stools. Emergency endoscopy revealed that the morphology of the gastric submucosal tumor had transformed into a pedunculated polyp-like morphology with a bleeding ulcer at the apex of the lesion. Endoscopic hemostasis using hemostatic forceps was performed. However, the patient continued to pass black stools. In light of the persistent symptoms and unique morphology of the lesion, endoscopic resection was attempted as a curative approach. The lesion was excised by hot snare polypectomy. Post-treatment, the patient exhibited no signs of recurrence, marking a successful resolution. Three months later, a gastroduodenal endoscopy showed that the excised site had undergone scar formation without recurrence of the lesion. This case holds significant clinical value as it demonstrates the efficacy of a minimally invasive treatment strategy in managing repeated bleeding ulcerations of an ectopic pancreas, ultimately achieving a complete cure.

Wernicke encephalopathy: limitations in a laboratory and radiological diagnosis.

Wernicke encephalopathy is an emergent neurological disorder caused by vitamin B1 (thiamine) deficiency. Here, we present a case of Wernicke encephalopathy in a male patient in his 70s with normal serum thiamine levels and MRI findings on admission. He had a history of heavy alcohol consumption and a gradual decrease in food intake. On arrival at the hospital, his consciousness was impaired which persisted even after glucose replacement. Moreover, horizontal nystagmus and cerebellar ataxia were observed. Head CT scan and MRI revealed no abnormal findings. Further, his serum thiamine level was within the normal range. The patient was clinically diagnosed with Wernicke encephalopathy, and high-dose thiamine therapy was started. Then, his symptoms improved immediately. Thus, in case of clinical suspicion, treatment for Wernicke encephalopathy must be initiated promptly even in patients with normal serum thiamine levels.

The usefulness of a newly invented transparent silicon attachment: static electricity fastening tape hood.

Video 1Presentation of a newly invented transparent silicon attachment, the static electricity fastening tape hood, and its creation process, durability, and usefulness for various endoscopic procedures.