Clinical outcomes and learning curve of Tip-in endoscopic mucosal resection for 15-25 mm colorectal neoplasms among non-experts.

BACKGROUND AND AIM: Tip-in endoscopic mucosal resection (EMR) has a high en bloc resection rate for large colorectal neoplasms. However, non-experts' performance in Tip-in EMR has not been investigated. We investigated whether Tip-in EMR can be achieved effectively and safely even by non-experts. METHODS: This retrospective study included consecutive patients who underwent Tip-in EMR for 15-25 mm colorectal nonpedunculated neoplasms at a Japanese tertiary cancer center between January 2014 and December 2020. Baseline characteristics, treatment outcomes, learning curve of non-experts, and risk factors of failing self-achieved en bloc resection were analyzed. RESULTS: A total of 597 lesions were analyzed (438 by experts and 159 by non-experts). The self-achieved en bloc resection (69.8% vs 88.6%, P < 0.001) and self-achieved R0 resection (58.3% vs 76.5%, P < 0.001) rates were significantly lower in non-experts with <10 cases of experience than in experts, but not in non-experts with >10 cases. Adverse event (P = 0.165) and local recurrence (P = 0.892) rates were not significantly different between experts and non-experts. Risk factors of failing self-achieved en bloc resection were non-polypoid morphology (OR 3.4, 95% CI 1.6-7.3, P = 0.001), lesions with an underlying semilunar fold (OR 3.6, 95% CI 1.6-7.3, P < 0.001), positive non-lifting sign (OR 3.1, 95% CI 1.2-8.0, P = 0.023), and non-experts with an experience of ≤10 cases (OR 3.6, 95% CI 2.1-6.3, P < 0.001). CONCLUSION: The clinical outcomes of Tip-in EMR for 15-25 mm lesions performed by non-experts were favorable.

Robot-assisted distal gastrectomy and local resection for gastric cancer and gastrointestinal stromal tumor.

Gastrointestinal stromal tumors surrounding the esophagogastric junction are often challenging to resect, with no consensus regarding the optimal surgical technique. Here in, we present a case of concurrent gastric cancer in the antrum and gastrointestinal stromal tumors adjacent to the esophagogastric junction. The patient underwent simultaneous distal gastrectomy and local resection assisted by a surgical robot, avoiding the need for total gastrectomy. The utilization of robot-assisted surgery has become an increasingly popular technique, holding promise for simplifying complex surgical procedures across diverse medical settings.

Gel immersion endoscopic mucosal resection for early gastric neoplasms: a multicenter case series study.

Several cases have been reported that suggest the efficacy of gel immersion endoscopic mucosal resection (GI-EMR) for gastric neoplasms. However, no study has evaluated treatment outcomes of GI-EMR for gastric neoplasms. This study aimed to investigate the efficacy and safety of GI-EMR for early gastric neoplasms. Nine patients (17 lesions) undergoing gastric GI-EMR were included, with a median lesion size of 10 mm (interquartile range [IQR] 5-13 mm). All lesions were protruding or flat elevated. The median procedure time was 3 minutes (IQR 2-5) and en bloc resection was achieved in all cases. Among 15 neoplastic lesions, the R0 resection rate was 86.7% (13/15 lesions). Adverse events included immediate bleeding requiring hemostasis in two cases, which was controlled endoscopically. No delayed bleeding or perforation occurred. In conclusion, GI-EMR may be a safe and effective treatment for early, small gastric neoplasms. However, due to the small sample in the present study, further investigation is required regarding the indication for this technique.

Evaluating false-positive detection in a computer-aided detection system for colonoscopy.

BACKGROUND AND AIM: Computer-aided detection (CADe) systems can efficiently detect polyps during colonoscopy. However, false-positive (FP) activation is a major limitation of CADe. We aimed to compare the rate and causes of FP using CADe before and after an update designed to reduce FP. METHODS: We analyzed CADe-assisted colonoscopy videos recorded between July 2022 and October 2022. The number and causes of FPs and excessive time spent by the endoscopist on FP (ET) were compared pre- and post-update using 1:1 propensity score matching. RESULTS: During the study period, 191 colonoscopy videos (94 and 97 in the pre- and post-update groups, respectively) were recorded. Propensity score matching resulted in 146 videos (73 in each group). The mean number of FPs and median ET per colonoscopy were significantly lower in the post-update group than those in the pre-update group (4.2 ± 3.7 vs 18.1 ± 11.1; P < 0.001 and 0 vs 16 s; P < 0.001, respectively). Mucosal tags, bubbles, and folds had the strongest association with decreased FP post-update (pre-update vs post-update: 4.3 ± 3.6 vs 0.4 ± 0.8, 0.32 ± 0.70 vs 0.04 ± 0.20, and 8.6 ± 6.7 vs 1.6 ± 1.7, respectively). There was no significant decrease in the true positive rate (post-update vs pre-update: 95.0% vs 99.2%; P = 0.09) or the adenoma detection rate (post-update vs pre-update: 52.1% vs 49.3%; P = 0.87). CONCLUSIONS: The updated CADe can reduce FP without impairing polyp detection. A reduction in FP may help relieve the burden on endoscopists.

A novel low-power pure-cut hot snare polypectomy for 10-14 mm colorectal adenomas: An ex vivo and a clinical prospective feasibility study (SHARP trial).

BACKGROUND AND AIM: Hot snare polypectomy using blend or coagulation current is widely used; however, it causes deeper tissue heat injury, leading to adverse events. We hypothesized that hot polypectomy using low-power pure cut current (PureCut, effect 1 10 W) could reduce deeper tissue heat injury. We conducted animal experiments to evaluate the deeper tissue heat injury and conducted a prospective clinical study to examine its cutting ability. METHODS: In a porcine rectum, hot polypectomy using Blend current (EndoCut, effect 3 40 W) and low-power pure cut current was performed. The deepest part of heat destruction and thickness of the non-burned submucosal layer were evaluated histologically. Based on the results, we performed low-power pure cut current hot polypectomy for 10-14 mm adenoma. The primary endpoint was complete resection defined as one-piece resection with negative for adenoma in quadrant biopsies from the defect margin. RESULTS: In experiments, all low-power pure-cut resections were limited within the submucosal layer whereas blend current resections coagulated the muscular layer in 13% (3/23). The remaining submucosal layer was thicker in low-power pure cut current than in blend current resections. In the clinical study, low-power pure-cut hot polypectomy removed all 100 enrolled polyps. For 98 pathologically neoplastic polyps, complete resection was achieved in 84 (85.7%, 95% confidence interval, 77-92%). The lower limit of the 95% confidence interval was not more than 15% below the pre-defined threshold of 86.6%. No severe adverse events occurred. CONCLUSIONS: A novel low-power pure-cut hot polypectomy may be feasible for adenoma measuring 10-14 mm. (UMIN000037678).

Ultrafast Geminate Recombination Facilitated by Hydrogen-Atom Transfer in Charge Transfer Reactions from Hydroxide and Methoxide Ions.

Previous transient absorption spectroscopy (TAS) hinted at an exceptionally rapid geminate recombination process in charge transfer reactions involving OH- or OD- ions in liquid water and CH3O- ions in liquid methanol. However, a comprehensive investigation of these dynamics using TAS has been hindered by the technical challenges stemming from the ultrafast spectral shift that spans a wide wavelength range from the mid-infrared to the visible on the subpicosecond time scale. To address these challenges, we have employed ultraviolet time-resolved photoelectron spectroscopy of aqueous solutions, enabling us to observe and analyze the complete dynamics, including electron detachment, solvation, and geminate recombination. Our findings are consistent with those of Iglev et al. ( J. Phys. Chem. Lett. 2015, 6, 986-992), supporting the hypothesis that the structural diffusion of OH/OD/CH3O induced by a presolvated electron plays a pivotal role in facilitating ultrafast geminate recombination.

Investigation of vertical margin involvement in endoscopic resection for T1 colorectal cancer.

OBJECTIVES: The resection of vertical margin-negative submucosally invasive colorectal cancer (CRC) relies on the pathological risk assessment of lymph node metastasis. However, no large-scale study has clarified the endoscopic resection (ER) outcome for submucosally invasive CRC, focusing on the vertical margin status. This retrospective study aimed to examine vertical margin involvement in ER for submucosally invasive CRC and explore the treatment consequences associated with vertical margin status. METHODS: We analyzed 395 submucosally invasive CRC cases in 389 patients who underwent ER at our hospital between 2008 and 2020. The presence of residual tumors and simultaneous lymph node metastasis in patients who underwent additional surgery was assessed and compared between the vertical incomplete ER and the vertical margin-negative groups. RESULTS: Among the patients, 270 were men, with a median age of 69 years. The vertical incomplete ER rate was 21.5%, with positive vertical margins and unclear vertical margins identified in 12.2% and 9.3% of the cases, respectively. Among 154 patients who underwent additional surgery after ER, the vertical incomplete ER group had a significantly higher residual tumor rate than the vertical margin-negative group (P = 0.001). The vertical incomplete ER group had a significantly higher lymph node metastasis rate than the vertical margin-negative group (P = 0.029). CONCLUSION: This study clarified the substantial risk of vertical incomplete ER in submucosally invasive CRC and revealed the high risk of residual tumor and lymph node metastasis in vertical incomplete ER for submucosal CRC.

Local recurrence risk of esophageal squamous cell carcinoma due to intralesional damage during endoscopic submucosal dissection.

BACKGROUND AND AIM: It is unclear whether additional treatment should be considered given the recurrence risk after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) when the vertical margin is positive or unclear (VM1/VMX) due to intralesional damage. This study aimed to elucidate the local recurrence risk of ESCC caused by intralesional damage during ESD. METHODS: Among consecutive patients with pT1a ESCCs initially treated by ESD at our institution between January 2006 and December 2018, ESCCs diagnosed as VM1/VMX were retrospectively reviewed. Exclusion criteria were piecemeal resection and any additional treatment after ESD. Intralesional damage included the following three types: a macroscopic hole inside the lesion, an incision from the lateral margin of the specimen into the lesion, and crushing injury or burn effect into the deepest area of the lesion without an obvious hole. The local recurrence rate after ESD was primarily analyzed. RESULTS: Of 1174 pT1a ESCCs initially treated using ESD, 22 lesions were histopathologically diagnosed as VM1/VMX due to intralesional damage (1.9%; 95% confidence interval [CI], 1.2-2.8%). At a median follow-up period of 60.0 (interquartile range, 15.0-84.0) months, no local recurrence was observed (0.0%; 95% CI, 0.0-13.3%) among 21 lesions finally evaluated. CONCLUSIONS: The impact of intralesional damage during ESD for ESCC on local recurrence might be negligible. Follow-up without additional treatment may be acceptable even if intralesional damage occurs and results in VM1/VMX after ESD for pT1a ESCCs.

Optimization of endoscopic ultrasound-guided tissue sample acquisition for commercially available comprehensive genome profiling.

BACKGROUND AND AIM: Optimal tumor samples are crucial for successful analysis using commercially available comprehensive genomic profiling (CACGP). However, samples acquired by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are occasionally insufficient, and no consensus on the optimal number of needle passes required for CACGP exists. This study aimed to explore the optimal number of needle passes required for EUS-TA to procure an ideal sample fulfilling the prerequisite criteria of CACGPs. METHODS: Patients who underwent EUS-TA for solid masses between November 2019 and July 2021 were retrospectively studied. The correlation between the acquisition rate of an ideal sample and the number of needle passes mounted on a microscope slide was evaluated. Additionally, the factors predicting a successful analysis were investigated in patients scheduled for CACGP using EUS-TA-obtained samples during the same period. RESULTS: EUS-TAs using 22- and 19-gauge (G) needles were performed in 336 and 57 patients, respectively. There was a positive correlation between the acquisition rate and the number of passes using a 22-G needle (38.9%, 45.0%, 83.7%, and 100% for 1, 2, 3, and 4 passes, respectively), while no correlation was found with a 19-G needle (84.2%, 83.3%, and 85.0% for 1, 2, and 3 passes, respectively). The analysis success rate in patients with scheduled CACGP was significantly higher with ideal samples than with suboptimal samples (94.1% vs 55.0%, P < 0.01). CONCLUSIONS: The optimal estimated number of needle passes was 4 and 1-2 for 22- and 19-G needles, respectively.

A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2.

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient's lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma. Systemic chemotherapy including an anti-PD-L1 antibody was effective for >1 year, but brain metastases developed. Pathology of the brain tumors showed mucinous adenocarcinoma without expression of MSH2 and MSH6, while multi-gene panel testing demonstrated not only high microsatellite instability and a high tumor mutation burden, but also germline BRCA2 variants. Further, germline testing in relatives confirmed both variants were from the paternal line, from which many LS-related cancers develop, but not BRCA-related cancer.

Efficacy and Safety of Gel Immersion Endoscopic Mucosal Resection for Non-Pedunculated Colorectal Polyps.

Underwater endoscopic mucosal resection (UEMR) has become a popular endoscopic resection method for large colorectal neoplasms. However, visualization can be poor during UEMR due to the presence of intestinal fluid. Gel immersion endoscopic mucosal resection (GIEMR), using a specially developed gel (Viscoclear®, Otsuka Pharmaceutical Factory, Tokushima, Japan), can improve the visual field. However, reports of GIEMR for colorectal polyps are limited. Herein, we evaluated the short-term outcomes of GIEMR for non-pedunculated colorectal neoplasms (NPCRN). This single-center, retrospective, and observational study includes 25 lesions in 20 patients with NPCRN who underwent GIEMR between January and October 2022. The short-term outcomes and adverse events were evaluated. The lesion locations were as follows: right colon, 18 lesions; left colon, 7 lesions; and rectum, none. The median tumor diameter was 15 (IQR, 10-18) mm. Histological classification was as follows: sessile serrated lesion, 9 cases; adenoma, 12 cases; and intramucosal adenocarcinoma, 4 cases. The overall en bloc resection rates and R0 resection rates were 80% (20/25) and 72% (18/25). For NPCRN in 10-19 mm, the en bloc resection rate was 75% (12/16), with an R0 resection rate of 69% (11/16). No post-polypectomy bleeding, perforation, or post-coagulation syndrome were observed. The findings of our study provide preliminary evidence of the efficacy and safety of GIEMR for NPCRN. Therefore, GIEMR may be a promising novel endoscopic resection method for NPCRN.

Distortion Correction of Low-Energy Photoelectron Spectra of Liquids Using Spectroscopic Data for Solvated Electrons.

Time-resolved photoelectron spectroscopy (TRPES) enables real-time observation of ultrafast electronic dynamics in solutions. When extreme ultraviolet (EUV) probe pulses are employed, they can ionize solutes from all electronic states involved in the dynamics. However, EUV pulses also produce a strong ionization signal from a solvent that is typically 6 orders of magnitude greater than the pump-probe photoelectron signal of solutes. Alternatively, UV probe pulses enable highly sensitive and selective observation of photoexcited solutes because typical solvents such as water are transparent to UV radiation. An obstacle in such UV-TRPES measurements is spectral distortion caused by electron scattering and a yet to be identified mechanism in liquids. We have previously proposed the spectral retrieval (SR) method as an a posteriori approach to removing the distortion and overcoming this difficulty in UV-TRPES; however, its accuracy has not yet been verified by comparison with EUV-TRPES results. In the present study, we perform EUV-TRPES for charge transfer reactions in water, methanol, and ethanol, and verify SR analysis of UV-TRPES. We also estimate a previously undetermined energy-dependent intensity factor and expand the basis sets for SR analysis. The refined SR method is employed for reanalyzing the UV-TRPES data for the formation and relaxation dynamics of solvated electrons in various systems. The electron binding energy distributions for solvated electrons in liquid water, methanol, and ethanol are confirmed to be Gaussian centered at 3.78, 3.39, and 3.25 eV, respectively, in agreement with Nishitani et al. [ Sci. Adv. 2019, 5(8), eaaw6896]. An effective energy gap between the conduction band and the vacuum level at the gas-liquid interface is estimated to be 0.2 eV for liquid water and 0.1 eV for methanol and ethanol.

Ultrafast Electronic Relaxation in 6-Methyluracil and 5-Fluorouracil in Isolated and Aqueous Conditions: Substituent and Solvent Effects.

We report ultrafast extreme ultraviolet photoelectron spectroscopy of 6-methyluracil (6mUra) and 5-fluorouracil (5FUra) in the gas phase and 6mUra and 5-fluorouridine in an aqueous environment. In the gas phase, internal conversion (IC) occurs from 1ππ* to 1nπ* states in tens of femtoseconds, followed by intersystem crossing to the 3ππ* state in several picoseconds. In an aqueous solution, 6mUra undergoes IC almost exclusively to the ground state (S0) in about 100 fs, which is essentially the same process as that for unsubstituted uracil, but much faster than that for thymine (5-methyluracil). The different dynamics for C5 and C6 methylation suggest that IC from 1ππ* to S0 is facilitated by out-of-plane (OOP) motion of the C5 substituent. The slow IC for C5-substituted molecules in an aqueous environment is ascribed to the solvent reorganization that is required for this OOP motion to occur. The slow rate for 5FUrd may arise in part from an increased barrier height due to C5 fluorination.

Ultrafast Ring Closure Reaction of Gaseous cis-Stilbene from S1(ππ*).

cis-Stilbene (cis-St) is a well-known benchmark system for cis-trans photoisomerization. cis-St also produces 4a,4b-dihydrophenanthrene (DHP) in solution with a quantum yield of less than 0.19. The ring closure reaction, however, has never been identified for gaseous cis-St, and a recent computational simulation predicted the quantum yield of DHP to be only 0.04. In the present study, we identified an ultrafast ring closure reaction of gaseous cis-St for the first time using extreme ultraviolet time-resolved photoelectron spectroscopy. Surface hopping trajectory calculations at the SA3-XMS-CASPT2(2,2) level of theory reproduce the features of the observed time-resolved photoelectron spectra and predict the cis-St:DHP:trans-St branching ratio to be 0.55:0.41:0.04, in contrast with previous estimates. The results indicate that photoexcited cis-St favors ring closure over cis-trans isomerization under the isolated condition.

Formation of Long-Lived Dark States during Electronic Relaxation of Pyrimidine Nucleobases Studied Using Extreme Ultraviolet Time-Resolved Photoelectron Spectroscopy.

Ultrafast electronic relaxation of nucleobases from 1ππ* states to the ground state (S0) is considered essential for the photostability of DNA. However, transient absorption spectroscopy (TAS) has indicated that some nucleobases in aqueous solutions create long-lived 1nπ*/3ππ* dark states from the 1ππ* states with a high quantum yield of 0.4-0.5. We investigated electronic relaxation in pyrimidine nucleobases in both aqueous solutions and the gas phase using extreme ultraviolet (EUV) time-resolved photoelectron spectroscopy. Femtosecond EUV probe pulses cause ionization from all electronic states involved in the relaxation process, providing a clear overview of the electronic dynamics. The 1nπ* quantum yields for aqueous cytidine and uracil (Ura) derivatives were found to be considerably lower (<0.07) than previous estimates reported by TAS. On the other hand, aqueous thymine (Thy) and thymidine exhibited a longer 1ππ* lifetime and a higher quantum yield (0.12-0.22) for the 1nπ* state. A similar trend was found for isolated Thy and Ura in the gas phase: the 1ππ* lifetimes are 39 and 17 fs and the quantum yield for 1nπ* are 1.0 and 0.45 for Thy and Ura, respectively. The result indicates that single methylation to the C5 position hinders the out-of-plane deformation that drives the system to the conical intersection region between 1ππ* and S0, providing a large impact on the photophysics/photochemistry of a pyrimidine nucleobase. The significant reduction of 1nπ* yield in aqueous solution is ascribed to the destabilization of the 1nπ* state induced by hydrogen bonding.

Endoscopic causes and characteristics of missed gastric cancers after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Because endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) preserves the entire stomach, missed gastric cancers (MGCs) are often found in the remaining gastric mucosa. However, the endoscopic causes of MGCs remain unclear. Therefore, we aimed to elucidate the endoscopic causes and characteristics of MGCs after ESD. METHODS: From January 2009 to December 2018, all patients undergoing ESD for initially detected EGC were enrolled. According to a review of EGD images before ESD, we identified the endoscopic causes (perceptual, exposure, sampling errors, and inadequate preparation) and characteristics of MGC in each endoscopic cause. RESULTS: Of 2208 patients who underwent ESD for initial EGC, 82 patients (3.7%) had 100 MGCs. The breakdown of endoscopic causes of MGCs was as follows: 69 (69%) perceptual errors, 23 (23%) exposure errors, 7 (7%) sampling errors, and 1 (1%) inadequate preparation. Logistic regression analysis showed that the risk factors for perceptual error were male sex (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.16-5.18), isochromatic coloration (OR, 3.17; 95% CI, 1.47-6.84), greater curvature (OR, 2.31; 95% CI, 1.121-4.40), and lesion size ≤12 mm (OR, 1.74; 95% CI, 1.07-2.84). The sites of exposure errors were around the incisura angularis (11 [48%]), posterior wall of the gastric body (6 [26%]), and antrum (5 [21%]). CONCLUSIONS: We identified MGCs in 4 categories and clarified their characteristics. Quality improvements in EGD observation, with attention to the risks of perceptual and site of exposure errors, can potentially prevent missing EGCs.

Charge Transfer Reactions from I- to Polar Protic Solvents Studied Using Ultrafast Extreme Ultraviolet Photoelectron Spectroscopy.

Charge transfer reactions from I- to solvent water, methanol, and ethanol were studied using extreme ultraviolet time-resolved photoelectron spectroscopy (EUV-TRPES). This technique eliminates spectral broadening, previously seen in UV-TRPES, caused by electron inelastic scattering in liquids, and enables clear observation of the temporal evolution of the spectral shape. The peak position, width, and intensity of the electron binding energy distribution indicate electron detachment and subsequent solvation and thermalization processes. Geminate recombination between detached electrons and iodine atoms is discussed using a diffusion equation and a global fitting analysis based on a kinetics model.

Clinical outcomes of endoscopic submucosal dissection for superficial circumferential esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Our aim was to elucidate the clinical outcomes of endoscopic submucosal dissection (ESD) for superficial circumferential esophageal squamous cell carcinoma (cESCC). METHODS: Consecutive patients who underwent ESD for cESCC between 2009 and 2020 were retrospectively reviewed. Short-term outcomes were en-bloc resection, R0 resection, procedure time, and adverse events, whereas long-term outcomes were overall survival (OS), disease-specific survival (DSS), cumulative recurrence rate (CRR), and clinical course. RESULTS: Fifty-two patients with 52 cESCCs (median tumor length, 5.0 cm; interquartile range [IQR], 4.0-6.3) were evaluated. The en-bloc resection and R0 resection rates were 100% (95% confidence interval [CI], 94.4-100) and 69.2% (95% CI, 54.9-81.3), respectively. The median procedure time was 112 minutes (IQR, 87-162). Intraoperative perforations and delayed bleeding occurred in 4 (7.7%) and 1 (1.9%) patients, respectively. Among the 42 patients who underwent ESD alone, 36 (85.7%) experienced esophageal strictures. Within a median follow-up of 49.1 months (IQR, 25.7-74.7), the 4-year OS, DSS, and CRR were 86.2% (95% CI, 71.6-93.6), 95.5% (95% CI, 83.1-98.9), and 11.5% (95% CI, 4.1-23.1), respectively. There was no significant difference in the OS between patients with low-risk cESCC (pT1a, negative lymphovascular invasion, and negative vertical margin) and high-risk lesions, regardless of undergoing additional treatment (P = .93). In 31 patients with low-risk cESCC who were treated with ESD alone, the 4-year OS, DSS, and CRR were 93.2%, 100%, and 0%, respectively. CONCLUSIONS: ESD is a highly curative treatment for cESCC with favorable long-term outcomes, especially in low-risk patients. Stricture-prevention techniques should be improved to optimize the benefits of ESD for cESCC.