Underwater endoscopic submucosal dissection for colorectal tumors decreases the incidence of post-electrocoagulation syndrome.

BACKGROUND AND AIMS: Underwater endoscopic submucosal dissection (U-ESD) is a recently developed procedure that has the potential to prevent post-ESD coagulation syndrome (PECS) owing to its heat-sink effect. We aimed to clarify whether U-ESD decreases the incidence of PECS compared with conventional ESD (C-ESD). METHODS: A total of 205 patients who underwent colorectal ESD (C-ESD: 125; U-ESD: 80) were analyzed. Propensity score matching analysis was performed to adjust for patient backgrounds. Ten C-ESD and two U-ESD patients with muscle damage or perforation during ESD were excluded when comparing PECS. The primary outcome was to compare the incidence of PECS between the U-ESD and C-ESD groups (54 matched pairs). Secondary outcomes were to compare procedural outcomes between the C-ESD and U-ESD groups (62 matched pairs). RESULTS: Among the 78 patients who underwent U-ESD, PECS occurred in only one patient (1.3%). Adjusted comparisons between the U-ESD and C-ESD groups demonstrated a significantly lower incidence of PECS in the U-ESD group (0% vs 11.1%; P = 0.027). Median dissection speed was significantly faster in the U-ESD than in the C-ESD group (10.9 mm2 /min vs 6.9 mm2 /min; P < 0.001). En bloc and complete resection rates were 100% in the U-ESD group. Although perforation and delayed bleeding occurred in one patient each (1.6%) as adverse events in the U-ESD group, there were no differences compared with the C-ESD group. CONCLUSIONS: Our study demonstrates that U-ESD effectively decreases the incidence of PECS and is a faster and safer method for colorectal ESD.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.

Targeted Metabolomic Profiling of Plasma Samples in Gastric Cancer by Liquid Chromatography-Mass Spectrometry.

INTRODUCTION: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. METHODS: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. RESULTS: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865-0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797-0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. CONCLUSION: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.

Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study.

BACKGROUND: A new scoring system, the BEST-J score, using ten risk factors to assign cases to different post-endoscopic submucosal dissection (ESD) risk groups for bleeding, has been shown to be accurate for risk stratification. We first aimed to validate the BEST-J score at four hospitals not specialized in performing ESD and then aimed to identify other risk factors for post-ESD bleeding. METHODS: We evaluated the incidence of post-ESD bleeding in 791 cases of early gastric cancer (EGC) between October 2013 and December 2020 as a retrospective, multi-center observational study conducted at four hospitals. Multivariate logistic regression models to examine the effect of independent variables on post-ESD bleeding firstly included ten possible factors raised by the BEST-J score and secondly included statistically significant (p < 0.01) in univariate analysis. The prediction accuracy of the model was evaluated by receiver-operating characteristic analysis and the areas under the curve (AUC). RESULTS: The incidence of post-ESD bleeding was 4.8% (38/791, 95% confidence interval [CI] 3.4-6.5%). On multivariate analysis, the risk factors were P2Y12 receptor antagonist (odds ratio [OR]: 5.870, 95% CI 1.624-21.219), warfarin (8.382, 1.658-42.322), direct oral anticoagulant (DOAC) (8.980, 1.603-50.322), and tumor location in lower third of stomach (2.151, 1.012-4.571), respectively. When we categorized cases into low-risk by BEST-J score, intermediate-risk, high-risk, and very high-risk groups, the bleeding rates were 2.8%, 7.3%, 12.8%, and 19.0%, respectively. The AUC for our cohort was 0.713 (95% CI 0.625-0.802) for the BEST-J score. In the multivariate analysis in our cohort, the risks were age, body mass index, P2Y12 receptor antagonist, warfarin, DOAC, respectively. DISCUSSION: The BEST-J score is equally accurate in risk stratification of patients with EGC for post-ESD bleeding at non-specialized facilities for ESD as in specialized hospitals. BMI and age may be helpful additional risk factors at hospitals not specialized.

Impact of perioperative antithrombotic strategies on clinical events in non-cardiac surgery.

Antithrombotic therapy including antiplatelet agents and anticoagulants are prescribed for secondary prevention in patients with established cardiovascular disease. Although antithrombotic therapy is often interrupted before non-cardiac surgery with or without perioperative bridging anticoagulation, the impact on thrombotic and bleeding events remains uncertain. A total of 360 patients chronically treated with antithrombotic therapy for secondary prevention underwent elective non-cardiac surgery under general anesthesia, with the complete interruption of antithrombotic agents. The study endpoints included all-cause death, thrombotic events, and major bleeding complications after surgical procedures. Of 360 patients, 190 (52.8%) and 200 (55.6%) received antiplatelet and anticoagulation perioperatively. Atrial fibrillation (32.8%) and coronary artery disease (22.5%) were the major indications for antithrombotic regimens. Antithrombotic therapy was interrupted from 5 [2, 7] days before the surgery to 4 [2, 7] days postoperatively. Perioperative bridging therapy with unfractionated heparin was employed in 113 (31.4%) patients. During the hospitalization, one (0.3%) patient died due to non-cardiovascular causes. Thrombotic events and major bleeding occurred in two (0.6%) and eight (2.2%) patients. Bridging therapy with heparin was significantly associated with an increased risk of bleeding events (5.3% vs. 0.8%, p = 0.02). Pre-operative bridging therapy with heparin and operative duration were significantly associated with bleeding complications. In the present study, complete interruption of antithrombotic therapy resulted in a few thrombotic events in patients undergoing elective non-cardiac surgery. Bridging therapy with heparin and longer operative duration were significantly associated with post-operative bleeding complications.

Differences of Recovery from Rocuronium-induced Deep Paralysis in Response to Small Doses of Sugammadex between Elderly and Nonelderly Patients.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complete recovery from rocuronium-induced muscle paralysis with sugammadex is reported to be delayed in elderly patients. The authors tested a hypothesis that recovery from deep neuromuscular block with low-dose sugammadex is slower (primary hypothesis) and incidence of recurarization is higher (secondary hypothesis) in elderly patients than in nonelderly patients. METHODS: In anesthetized elderly (n = 20; 76.9 ± 5.0 yr of age) and nonelderly patients (n = 20; 53.7 ± 12.8 yr of age) under deep paralysis with rocuronium, change of train-of-four ratio per minute (primary outcome variable) was measured with an acceleromyograph neuromuscular monitor during spontaneous recovery from rocuronium-induced muscle paralysis (0.6 mg/kg) and after infusion of low-dose sugammadex (50 µg · kg · min). Recurarization was defined as the negative change of train-of-four ratio. RESULTS: Spontaneous train-of-four ratio recovery rate was significantly slower in the elderly group (median [25th percentile, 75th percentile]: 1.89 [1.22, 2.90] %/min) than in the nonelderly group (3.45 [1.96, 4.25] %/min, P = 0.024). Train-of-four ratio change rate in response to low-dose sugammadex was significantly slower in elderly (0.55 [-0.29, 1.54] %/min) than in the nonelderly group (1.68 [0.73, 3.13] %/min, P = 0.024). Incidence of recurarization was significantly higher in the elderly group than in the nonelderly group (35% vs. 5%, P = 0.044). Multiple linear regression analyses indicate that slower spontaneous train-of-four ratio recovery rate and impaired renal function are two major contributing factors that decrease train-of-four ratio change rate in response to low-dose sugammadex. CONCLUSIONS: Elderly patients are at greater risk for recurarization and residual muscle paralysis when low-dose sugammadex is administered.

Rebleeding Risk of Acute Hemorrhagic Rectal Ulcer: A Multicenter Retrospective Study.

Objective Acute hemorrhagic rectal ulcer (AHRU) is characterized by sudden, painless, and massive bleeding from rectal ulcers. To date, few studies have analyzed the risk factors for AHRU rebleeding. In this study, we clarified the risk factors of rebleeding after initial hemostasis of AHRU through a multicenter study. Methods A total of 149 patients diagnosed with AHRU between January 2015 and May 2020 at 3 medical centers were enrolled. We retrospectively investigated the following factors: age, sex, body mass index (BMI), performance status (PS), Charlson Comorbidity Index (CCI), comorbidities, medications, laboratory examinations, endoscopic findings, view of the entire rectum on endoscopy, hemostasis method, blood transfusion history, shock, instructions for posture change after initial hemostasis, and clinical course. Results Rebleeding was observed in 35 (23%) of 149 patients. A multivariate analysis showed that significant factors for rebleeding were PS 4 [odds ratio (OR), 5.23; 95% confidence interval (CI), 1.97-13.9; p=0.001], a blood transfusion history (OR, 3.66; 95% CI, 1.41-9.51; p=0.008), low an estimated glomerular filtration rate (eGFR) levels (OR, 0.98; 95% CI, 0.97-0.99; p=0.001), poor view of the whole rectum on endoscopy (OR, 0.33; 95% CI, 0.12-0.90; p=0.030), and use of monopolar hemostatic forceps (OR, 4.89; 95% CI, 1.37-17.4; p=0.014). Conclusion Factors associated with rebleeding of AHRU were a poor PS (PS 4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Successful planned piecemeal endoscopic resection using gel immersion and an over-the-scope clip for a lesion extensively extended into the colonic diverticulum.

Video 1Successfully planned piecemeal endoscopic resection using gel immersion and an over-the-scope clip for a lesion extensively extended into the colonic diverticulum.

Significance of rescue hybrid endoscopic submucosal dissection in difficult colorectal cases.

BACKGROUND/AIMS: Hybrid endoscopic submucosal dissection (ESD), in which an incision is made around a lesion and snaring is performed after submucosal dissection, has some advantages in colorectal surgery, including shorter procedure time and preventing perforation. However, its value for rescue resection in difficult colorectal ESD cases remains unclear. This study evaluated the utility of rescue hybrid ESD (RH-ESD). METHODS: We divided 364 colorectal ESD procedures into the conventional ESD group (C-ESD, n=260), scheduled hybrid ESD group (SH-ESD, n=69), and RH-ESD group (n=35) and compared their clinical outcomes. RESULTS: Resection time was significantly shorter in the following order: RH-ESD (149 [90-197] minutes) >C-ESD (90 [60-140] minutes) >SH-ESD (52 [29-80] minutes). The en bloc resection rate increased significantly in the following order: RH-ESD (48.6%), SH-ESD (78.3%), and C-ESD (97.7%). An analysis of factors related to piecemeal resection of RH-ESD revealed that the submucosal dissection rate was significantly lower in the piecemeal resection group (25% [20%-30%]) than in the en bloc resection group (40% [20%-60%]). CONCLUSION: RH-ESD was ineffective in terms of curative resection because of the low en bloc resection rate, but was useful for avoiding surgery.

Visibility of early gastric cancers by texture and color enhancement imaging using a high-definition ultrathin transnasal endoscope.

We evaluated whether texture and color enhancement imaging (TXI) using a high-definition ultrathin transnasal endoscope (UTE) improves the visibility of early gastric cancer (EGC) compared with white-light imaging (WLI). This study included 31 EGCs observed by TXI mode 2 using a high-definition UTE prior to endoscopic submucosal dissection. The first outcome was to compare the color differences based on Commission Internationale de l'Eclairage L*a*b* color space between EGCs and the surrounding mucosa by WLI and TXI using the UTE (objective appearance of EGC). The second outcome was to assess the visibility of EGCs by WLI and TXI using the UTE in an image evaluation test performed on 10 endoscopists (subjective appearance of EGC). Color differences between EGCs and non-neoplastic mucosa were significantly higher in TXI than in WLI in all EGCs (TXI: 16.0 ± 10.1 vs. WLI: 10.2 ± 5.5 [mean ± standard deviation], P < 0.001). Median visibility scores evaluated by 10 endoscopists using TXI were significantly higher than those evaluated using WLI (TXI: 4 [interquartile range, 4-4] vs. WLI: 4 [interquartile range, 3-4], P < 0.001). TXI using high-definition UTE improved both objective and subjective visibility of EGCs compared with WLI.

Endoscopic submucosal dissection using traction by a spring-and-loop with clip for a laterally spreading tumor in the inferior aspect of the cecum: a nonreferral center experience.

Video 1Endoscopic submucosal dissection using traction by a spring-and-loop with clip for a laterally spreading tumor in the inferior aspect of the cecum: a nonreferral center experience.

Transcatheter aortic valve implantation for severe aortic stenosis in a patient with mucopolysaccharidosis type II (Hunter syndrome) accompanied by severe airway obstruction.

Mucopolysaccharidosis type II, known as Hunter syndrome, is a rare inherited metabolic disorder with glycosaminoglycan accumulation leading to progressive multisystem involvement, such as heart, respiratory, and central nervous systems. In particular, concurrence of major heart and respiratory problems in this syndrome often causes difficulty in performing curative and invasive treatments. Transcatheter aortic valve implantation (TAVI) has been an established therapy for severe aortic stenosis (AS). In patients who cannot undergo surgical aortic valve replacement because of high risk for general anesthesia, TAVI with local anesthesia has become an alternative therapy for severe AS. We report herein a case of 50-year-old man with Hunter syndrome accompanied by severe airway obstruction who underwent TAVI with local anesthesia for severe AS. .

A case of early rectal carcinoma with submucosal tumor-like morphology.

Submucosal tumor (SMT)-like colorectal cancer is relatively rare. The patient was a 59-year-old man who underwent colonoscopy after a positive fecal occult blood test. Colonoscopy showed a protruded lesion of 10 mm in the lower rectum. On initial observation, conventional endoscopy showed that the lesion was covered with normal mucosa and its surface was reddish with small dimples. A neuroendocrine tumor was suspected, and a biopsy was performed, but the pathological diagnosis was adenocarcinoma. Re-examination 3 weeks later showed a depression at the surface of the lesion owing to the biopsy. Magnifying NBI showed a vessel pattern of uneven and irregular distribution, and an irregular surface pattern in the depressed area. Magnifying observations with crystal violet staining showed irregular pit patterns. The preoperative diagnosis was submucosal invasive cancer, and operation was performed. The final pathological diagnosis was well-differentiated tubular adenocarcinoma with deep submucosal invasion. The tumor was primarily localized in the submucosal layer and was covered by non-neoplastic mucosa except for the depressed area. The tumor was not exposed on the surface and was proliferating under the mucosa, which resulted in an SMT-like morphology. Our present case indicates that colorectal cancers should be differentially considered when SMT lesions are detected.

Evidence for the direct interaction of spermine with the inwardly rectifying potassium channel.

The inwardly rectifying potassium channel (Kir) regulates resting membrane potential, K+ homeostasis, heart rate, and hormone secretion. The outward current is blocked in a voltage-dependent manner, upon the binding of intracellular polyamines or Mg2+ to the transmembrane pore domain. Meanwhile, electrophysiological studies have shown that mutations of several acidic residues in the intracellular regions affected the inward rectification. Although these acidic residues are assumed to bind polyamines, the functional role of the binding of polyamines and Mg2+ to the intracellular regions of Kirs remains unclear. Here, we report thermodynamic and structural studies of the interaction between polyamines and the cytoplasmic pore of mouse Kir3.1/GIRK1, which is gated by binding of G-protein betagamma-subunit (Gbetagamma). ITC analyses showed that two spermine molecules bind to a tetramer of Kir3.1/GIRK1 with a dissociation constant of 26 microM, which is lower than other blockers. NMR analyses revealed that the spermine binding site is Asp-260 and its surrounding area. Small but significant chemical shift perturbations upon spermine binding were observed in the subunit-subunit interface of the tetramer, suggesting that spermine binding alters the relative orientations of the four subunits. Our ITC and NMR results postulated a spermine binding mode, where one spermine molecule bridges two Asp-260 side chains from adjacent subunits, with rearrangement of the subunit orientations. This suggests the functional roles of spermine binding to the cytoplasmic pore: stabilization of the resting state conformation of the channel, and instant translocation to the transmembrane pore upon activation through the Gbetagamma-induced conformational rearrangement.