Submucosal Injection Using Epinephrine-Added Saline in Cold Snare Polypectomy for Colorectal Polyps Shortens Time Required for Resection: A Randomized Controlled Study.

AIMS: Immediate bleeding after cold snare polypectomy (CSP) for colorectal polyps might interfere with confirmation of residuals and prolong the time required for resection. We investigated whether submucosal epinephrine-added saline injection reduces the time required for the CSP procedure. METHODS: We conducted a single-center, prospective, randomized controlled trial (clinical trial registration number: UMIN000046770). Patients with colorectal polyps ≤ 10 mm were randomly allocated to either CSP with epinephrine-added submucosal injection (CEMR group) or conventional CSP (CSP group). The primary outcome was the time required for resection defined as the time from the initiation of resection (the first insertion of the snare in the CSP group or the injection needle in the CEMR group) to the end of resection (confirming complete resection endoscopically after recognizing the cessation of immediate bleeding) in each lesion, and the secondary outcome was the time to spontaneous cessation of immediate bleeding after resection defined as the time from ensnaring the lesion to confirming the spontaneous cessation of immediate bleeding. RESULTS: A total of 126 patients were randomly assigned. Finally, 261 lesions in 118 patients (CEMR group, n = 59; CSP group, n = 59) were analyzed. The time required for resection calculated using the least-square mean was significantly shorter in the CEMR group (106.3 s, 95% CI 97.5 to 115.4 s) than in the CSP group (130.9 s, 95% CI 121.2 to 140.7 s) (P < 0.001). The time to spontaneous cessation of immediate bleeding was also significantly shorter in the CEMR group (20.4 s, 95% CI 14.3 to 26.5 s) than in the CSP group (74.2 s, 95% CI 67.6 to 80.7 s) (P < 0.001). Neither group had cases requiring hemostasis, perforation, or delayed bleeding. CONCLUSIONS: CEMR shortened the time for resection by shortening the time to cessation of immediate bleeding compared with conventional CSP in colorectal polyps ≤ 10 mm.

Hemostasis using a covered self-expandable metal stent for pseudoaneurysm bleeding from the perihilar bile duct.

Although there are many reports of hemostasis with covered self-expandable metal stent (CSEMS) for bleeding from the papilla of Vater and the intrapapillary and distal bile duct, there are rare reports of its use for hemostasis in the perihilar bile duct. We report the case of a patient undergoing supportive care for perihilar cholangiocarcinoma with acute cholecystitis after side-by-side placement of uncovered SEMS for perihilar bile duct obstruction. Percutaneous transhepatic gallbladder aspiration was performed upon admission, and hematemesis occurred the next day. Since computed tomography scanning showed a pseudoaneurysm in the right uncovered SEMS, hemostasis by interventional radiology (IVR) was performed thrice for massive bleeding; however, hemostasis could not be achieved. When endoscopic retrograde cholangiopancreatography was performed for scrutiny and treatment of melena and increased hepatobiliary enzyme, the endoscopic visual field could not be secured by bleeding, and changes in hemodynamics were observed; thus, IVR was required, but it was difficult to perform. Since bleeding from the right bile duct was expected, hemostasis was performed using CSEMS. This is the first report of hemostasis performed by placing a covered SEMS for bleeding from a pseudoaneurysm of the intrahepatic bile duct.

Risk Factors Indicating Difficulty During Gastric Endoscopic Submucosal Dissection for Inexperienced Endoscopists: A Retrospective Study.

AIM: Factors that may make endoscopic submucosal dissection (ESD) difficult for operators have been evaluated according to results based on the performance of experienced endoscopists. This study aimed to verify the predictors of difficult gastric ESD for ESD beginners. METHODS: From January 2015 to December 2021, 466 superficial gastric neoplasms were treated with ESD at Showa University Hospital. Excluding 103 lesions that performed ESD by experts who experienced more than 80 ESDs, a total of 363 lesions were included. The lesions were divided into two groups according to the ESD performance experience of the operator: ESD beginner (EB; ESD experience≤30 cases) and ESD intermediate (EI; ESD experience 31-80 cases) groups. Relationships between difficult ESD (having at least one of the following: procedure time>60 min, incomplete resection, change of operator, and occurrence of severe complications) and clinicopathological findings of the lesion were analyzed. RESULTS: The complete resection rates and the difficult ESD rates in the EB and EI groups were 99.3%, 94.8%, and 61.2%, 50.7%, respectively. In the EB group, univariate analysis showed that difficult ESD rate was significantly higher in the non-lower third lesions, the lesser curvature lesions, and cancerous lesions. In the EI group, univariate analysis showed that difficult ESD rate was significantly higher in lesion with ≥20 mm size, lesser curvature lesions, lesions with ulcers, and submucosal cancers. Multivariate analysis showed that the lesser curvature location and cancerous histology in the EB group and ≥20 mm lesion size, the lesser curvature location and submucosal invasion in the EI group were independent predictors of difficult ESD. CONCLUSIONS: The lesser curvature location is recognized as independent ESD difficulty factor for both beginners and intermediates. Cases with lesions located in the lesser curvature should not be selected for gastric ESD training by beginners.

Frequent and Specific Involvement of Changes of the p16-RB Pathway in Esophageal Neuroendocrine Carcinoma.

AIM: This study investigated the immunohistochemical expression of retinoblastoma (RB) protein and p16 protein in 10 neuroendocrine carcinomas (NECs), in comparison to two mixed-type NECs; 28 squamous cell carcinomas (SCCs), and 12 carcinosarcomas (CSs) from patients with esophageal cancer. MATERIALS AND METHODS: Immunohistochemical staining was performed using the avidin-biotin complex detection method. The staining was evaluated as diffusely positive, heterogeneous (in 5-95% of tumor cells), or diffusely negative. RESULTS: The combination of a diffuse loss of RB and the diffuse overexpression of p16, which is found in highly aggressive malignant tumors and is considered to convincingly suggest changes in the p16-RB pathway, was found in all NECs (10/10). In contrast no mixed-type NECs, one SCC and one CS showed this finding. Coexisting intraepithelial carcinoma was detected in seven NECs and only one lesion showed the combination of diffuse RB loss and p16 overexpression. CONCLUSION: These data suggest that changes in the p16-RB pathway were universally and specifically involved in the development and invasion of esophageal NECs and that it may be a useful diagnostic marker and a potential therapeutic target.

Electric polarizability of DNA in aqueous salt solution.

Monte Carlo simulations are performed to determine the anisotropy of the electric polarizability of a model DNA fragment in aqueous salt solution. By taking into consideration the participation of coions in the electroneutrality condition, at every simulation step, we obtain a list of counterions constituting the net charge arranged in increasing order of their distance from the DNA and calculate the contribution to the dipole moment from the first n counterions in the list. We define a partial polarizability tensor due to these n counterions to understand the origin of the polarizability in close relation to the solution structure. The ionic distributions are described by the counterion condensation theory. Characteristic features of the electric properties of polyelectrolytes are reproduced. The anisotropy of the electric polarizability Deltaalpha of DNA decreases with the addition of salt, yielding values comparable to experiment. The effect of electrophoretic motion of the polyion is examined by estimating its upper limit.

Thickness monitoring of optical filters for DWDM applications.

A method for thickness monitoring and turning-point prediction during deposition of narrow band pass optical filters (NBPF) for dense-wavelength-division-multiplexing (DWDM) applications is proposed. The method is based on a recurrent approach, with relative transmittance .tting, and includes partial coherence and monochromator bandpass e.ects. We show that the partial coherence e.ects in thin .lm structures are signi.cant and can not be neglected. The proposed method is applicable for precise thickness monitoring and deposition control of any complex multilayer coating.

[Assay method for uracil, dihydrouracil, 5-fluorouracil and 5-fluoro-5, 6-dihydrouracil by high-performance liquid chromatography].

In humans, 80-90% of the administered dose of 5-fluorouracil (5-FU) is degraded by dihydropyrimidine dehydrogenase (DPD), the initial rate-limiting enzyme in pyrimidine catabolism. In a previous report, the concentration ratio of uracil (U) and its dihydrogenated metabolite dihydrouracil (DHU) in human plasma before 5-FU treatment was found to be useful as an index of optimal 5-FU dosage, and was reported to be helpful in identifying patients with metabolic deficiency and anticipated risk of toxicity. We established an assay method for U, DHU, 5-FU and 5-fluoro-5,6-dihydrouracil (5-FDHU) in human serum and rat plasma using reverse-phase HPLC. After deproteinization of serum or plasma with perchloric acid, the supernatant was injected into HPLC with a column switching device and quantitated by UV detection. Separation was achieved by 3 columns whose characters were different and a mobile phase of 5 mmol/l sulfuric acid. In normal human serum, concentrations of U and DHU were 7.67-12.1 ng/ml and 70.4-103 ng/ml respectively, giving a DHU/U concentration ratio of 7.59-11.8. We determined U and DHU concentrations in rat plasma administered with 5-FU, and examined the correlation between DHU/U concentration ratio and DPD activity in the liver. Consequently, it was confirmed that U and DHU concentrations in rat plasma and DHU/U ratio were affected by 5-FU treatment. Also, there was a weakly significant, positive correlation between plasma DHU/U ratio and liver DPD activity (r = 0.44, p = 0.035). We expect that the serum DHU/U ratio obtained easily with this method can be utilized as a new index for safety with 5-FU treatment.

High-performance liquid chromatographic determination of oxatomide and its metabolite and its application to pharmacokinetic study in rat plasma.

Oxatomide (CAS 60607-34-3) is an antiallergic agent effective against allergic rhinitis, urticaria, pruritus dermatitis, eczema dermatitis and bronchial asthma. The aim of this study was to establish the method for simultaneously determining oxatomide and its major metabolite M-11 in human serum, human plasma and rat plasma by high-performance liquid chromatography (HPLC). The method was applied to study the influences of alimentation on pharmacokinetics of oxatomide in rats. After extracting oxatomide and its metabolite M-11 from human serum, human plasma or rat plasma with diethyl ether under alkaline condition, sulfuric acid was added to the organic layer and oxatomide and M-11 were back-extracted. The aqueous layers were analysed by HPLC equipped with a fluorimetric detector. The method was highly sensitive and precise for quantitation of oxatomide and M-11 in human serum, human plasma and rat plasma in the concentration range of 1 to 125 ng/ml. Plasma concentration of oxatomide decreased biphasically with an elimination half-life (T1/2) of 1.59 h after intravenous administration of oxatomide (1 mg/kg) to non-fasting male rats. After oral administration of oxatomide (30 mg/kg) to fasting male rats, plasma concentration of oxatomide increased rapidly, and reached the maximum concentration of 188 ng/ml (Cmax) at 1.0 h. Plasma concentration of oxatomide decreased monophasically. The T1/2 was 2.58 h. The bioavailability was 6.74%. Plasma concentration of M-11 increased rapidly, and reached Cmax of 64.3 ng/ml at 0.7 h, and decreased monophasically with T1/2 of 3.79 h. After oral administration of oxatomide to non-fasting male rats, plasma concentration of oxatomide reached Cmax of 378 ng/ml at 3.3 h. The T1/2 was 3.27 h and the bioavailability was 17.5%. The Cmax and AUC0-infinity of M-11 were larger than those after oral administration of oxatomide to fasting male rats. These results demonstrated the usefulness of this method for monitoring and basic examination of biological samples and the influence of alimentation on absorption of oxatomide. Determination of plasma oxatomide concentrations would provide a useful indication of therapeutic efficacy.