Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

Prospective study on the risk of transmission due to droplets and aerosols during an endoscopic procedure and the usefulness of extraoral suction devices.

OBJECTIVES: Endoscopy poses a high risk of severe acute respiratory syndrome coronavirus 2 infection for medical personnel due to the dispersal of aerosols from the patient. We investigated the location and size of droplets generated during esophagogastroduodenoscopy (EGD) and endoscopic submucosal dissection (ESD), the contamination of the surrounding area before and after the procedures, and the effectiveness of using an extraoral suction device (Free arm arteo; TOKYO GIKEN, Inc., Tokyo, Japan). METHODS: Patients who consented to the study and underwent EGD or ESD between December 8, 2020, and April 15, 2021, at the National Cancer Center East Hospital were included. Adenosine triphosphate (ATP) hygiene monitoring tests and a particle counter were used for measurements. RESULTS: Assessments were performed on 22 EGD and 15 ESD cases. ATP hygiene monitoring tests showed significant elevations at three sites near the patient, and two sites 1.5 m away, for EGD, and at four sites near the patient and 1.5 m away for ESD. In both ESD and EGD, extraoral suction devices reduced the extent of the contamination. Particles <5 µm in size were generated during endoscopic procedures and dispersed from both the forceps hole and the patient's mouth. The extraoral suction device did not reduce the number of particles generated. CONCLUSIONS: During endoscopic procedures, cleaning the surrounding environment is important in addition to standard precautions the endoscopist and caregivers take. The use of extraoral suction devices can also potentially reduce contamination of the surrounding environment.

Usefulness of endoscopic ultrasound in predicting treatment efficacy of salvage endoscopic therapy for local failure after chemoradiotherapy for esophageal squamous cell carcinoma.

BACKGROUND: Salvage endoscopic therapy, including endoscopic resection (ER) and photodynamic therapy (PDT), is effective for esophageal squamous cell carcinoma (ESCC) in local failure after chemoradiotherapy (CRT). Resection with pathologically vertical margin-negative (VM0) for ER and local complete response (L-CR) for PDT are important surrogate prognostic markers for each therapy's efficacy. We aimed to evaluate the usefulness of endoscopic ultrasound (EUS) in predicting the efficacy of salvage endoscopic therapy in local failure after CRT for ESCC. METHODS: We included patients who underwent EUS followed by ER or PDT for local failure after CRT or radiotherapy for ESCC from 2006 to 2020. We evaluated EUS findings associated with VM0 resection for ER and L-CR for PDT, which included the status of the outermost part of the submucosal layer, tumor thickness, and tumor invasion length into the muscularis propria (MP) layer. RESULTS: Thirty and 47 patients were enrolled into the ER and PDT groups, respectively. The VM0 resection rate in the ER group was 87% (26/30). The EUS findings associated with VM0 resection were tumor thickness < 2.3 mm (p = 0.01) and preserved hyperechoic line of the outermost part of the submucosa layer (p < 0.01). The L-CR rate in the PDT group was 69% (32/47). The EUS findings associated with L-CR were tumor thickness < 5.0 mm (p < 0.01) and tumor invasion length into the MP layer < 1.6 mm (p = 0.03). CONCLUSIONS: EUS can be useful in predicting the efficacy of salvage endoscopic treatment for local failure after CRT for ESCC.

Long-term clinical outcome after endoscopic resection of esophageal squamous cell carcinoma invading the muscularis mucosae without lymphovascular invasion.

BACKGROUND AND AIMS: Lymph node recurrence (LNR) after endoscopic resection (ER) in patients with esophageal squamous cell carcinoma (ESCC) pathologically invading the muscularis mucosae (pMM) without lymphovascular invasion (LVI) has been reported as non-negligible in the ER guidelines for esophageal cancer by the Japan Gastroenterological Endoscopy Society. However, these data were not regarded as high-level evidence because several retrospective case series were tabulated without sufficient long-term follow-up. Hence, this guideline stated that the administration of additional treatment after ER could not be determined for this population. This study aimed to clarify the long-term clinical outcomes after ER of pMM ESCC without LVI. METHODS: Between January 2009 and November 2017, we enrolled followed patients who underwent ER and were diagnosed with pMM ESCC without LVI with no additional treatments. We retrospectively investigated the cumulative recurrence rate and recurrence-free, overall, and disease-specific survival at 5 years after ER. RESULTS: Eighty-seven patients were enrolled. During the median follow-up period of 64 months (range, 12-117), 3 patients developed lymph node and/or distant recurrence, and 2 of these cases occurred more than 3 years after ER; all 3 patients died of the primary disease. The 5-year cumulative recurrence rate was 4.3%, and the 5-year recurrence-free, disease-specific, and overall survival rates were 88.8%, 98.2%, and 91.7%, respectively. CONCLUSIONS: The long-term outcome for patients with pMM ESCC without LVI was favorable after ER; however, this population had a risk of recurrence directly leading to death. Long-term follow-up is necessary, with attention to the timing of recurrence.

The safety and feasibility of endoscopic submucosal dissection using a flexible three-dimensional endoscope for early gastric cancer and superficial esophageal cancer: A prospective observational study.

BACKGROUND AND AIM: Endoscopic submucosal dissection (ESD) is performed as one of standard treatments for patients with early gastric cancer (EGC) and superficial esophageal squamous cancer (SESCC). A prototype of a flexible endoscope with a 3-D system has been recently developed. This study aimed to investigate the safety and feasibility of ESD using a 3-D flexible endoscope (3-D ESD) for EGC and SESCC. METHODS: This single-center, prospective, observational study enrolled patients who underwent planned 3-D ESD. The clinical outcomes, including the incidence of adverse events and treatment results, were analyzed. Visibility and manipulation during 3-D ESD were evaluated using a visual analog scale (VAS). We also evaluated the effect of the 3-D system on the endoscopist using VAS and the critical flicker fusion frequency (CFFF). RESULTS: We analyzed 47 EGC and 20 SESCC cases. There are no bleeding cases that required transfusion and perforation during 3-D ESD in both EGC and SESCC patients. However, the incidence of delayed bleeding and delayed perforation was 1.5% (one case) each. The mean VAS scores for recognizing the submucosal layer during the submucosal dissection, visual perception of blood vessel, and depth perception were 72.7 ± 22.2, 74.7 ± 21.8, and 78.2 ± 19.9, respectively. In contrast, the mean VAS score for manipulation was 25.4 ± 19.7. Among endoscopists, there was no significant difference in the VAS of eyestrain and headache before and after ESD, and there was no significant difference in the CFFF. CONCLUSION: The safety and feasibility of 3-D ESD for EGC and SESCC are acceptable in both patients and endoscopists.

Salvage endoscopic resection for cT1N0M0 local recurrence after chemoradiotherapy for esophageal squamous cell carcinoma: endoscopic submucosal dissection versus endoscopic mucosal resection.

OBJECTIVES: Salvage endoscopic resection is recommended when the local recurrence at primary site after chemoradiotherapy for esophageal squamous cell carcinoma is localized and superficial. This retrospective study aimed to comparatively analyse the short-term outcomes and local control of salvage endoscopic submucosal dissection versus salvage endoscopic mucosal resection for local recurrence after chemoradiotherapy or radiotherapy. METHODS: A total of 96 patients who underwent initial salvage endoscopic resection for cT1N0M0 local recurrence after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma between December 1998 and August 2019 patients were assigned to either the salvage endoscopic submucosal dissection (40 patients; 40 lesions) or salvage endoscopic mucosal resection (56 patients; 56 lesions) group. We evaluated the en bloc and R0 resection rates, severe adverse events and local failure rate after salvage endoscopic resection. Multivariate analysis was conducted to identify risk factors of local failure after salvage endoscopic resection. RESULTS: The en bloc resection rate was significantly higher in the salvage endoscopic submucosal dissection group than in the salvage endoscopic mucosal resection group (95% versus 63%; P < 0.001). There were no differences in R0 resection rate between the two groups (73% versus 52%, P = 0.057). One patient (3%) in the salvage endoscopic submucosal dissection group had perforation. The 3-year cumulative local failure rate of salvage endoscopic mucosal resection was significantly higher than that of salvage endoscopic submucosal dissection (27% versus 5%, P = 0.032). In multivariate analysis, salvage endoscopic mucosal resection (hazard ratio: 2.7, P = 0.044) was the only independent risk factor of local failure after salvage endoscopic resection. CONCLUSIONS: Salvage endoscopic submucosal dissection is the effective treatment for local recurrence based on the short-term outcomes and local efficacy.

The characteristics of missed pharyngeal and laryngeal cancers at gastrointestinal endoscopy.

OBJECTIVES: Understanding the miss rate and characteristics of missed pharyngeal and laryngeal cancers during upper gastrointestinal endoscopy may aid in reducing the endoscopic miss rate of this cancer type. However, little is known regarding the miss rate and characteristics of such cancers. Therefore, the aim of this study was to investigate the upper gastrointestinal endoscopic miss rate of oro-hypopharyngeal and laryngeal cancers, the characteristics of the missed cancers, and risk factors associated with the missed cancers. METHODS: Patients who underwent upper gastrointestinal endoscopy and were pathologically diagnosed with oro-hypopharyngeal and laryngeal squamous cell carcinoma from January 2019 to November 2020 at our institution were retrospectively evaluated. Missed cancers were defined as those diagnosed within 15 months after a negative upper gastrointestinal endoscopy. RESULTS: A total of 240 lesions were finally included. Eighty-five lesions were classified as missed cancers, and 155 lesions as non-missed cancers. The upper gastrointestinal endoscopic miss rate for oro-hypopharyngeal and laryngeal cancers was 35.4%. Multivariate analysis revealed that a tumor size of <13 mm (odds ratio: 1.96, P=0.026), tumors located on the anterior surface of the epiglottis/valleculae (odds ratio: 2.98, P=0.045) and inside of the pyriform sinus (odds ratio: 2.28, P=0.046) were associated with missed cancers. CONCLUSIONS: This study revealed a high miss rate of oro-hypopharyngeal and laryngeal cancers during endoscopic observations. High-quality upper gastrointestinal endoscopic observation and awareness of missed cancer may help reduce this rate.

The usefulness of a double-balloon endolumenal interventional platform for colorectal endoscopic submucosal dissection by non-expert endoscopists in a porcine model (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is an optimal treatment for colorectal tumors; however, it is technically difficult, especially for non-experts. Therefore, a device that helps non-experts perform colorectal ESD would be beneficial. A double-balloon endolumenal interventional platform (DEIP) was recently developed to assist colorectal ESD through endoscope stabilization and traction. This study assessed the usefulness of colorectal ESD using the DEIP (DEIP-ESD) by endoscopists, including non-experts, in a living porcine model. METHODS: Two pigs were used to perform eight DEIP-ESD and eight conventional cap-assisted ESD (C-ESD) procedures. Three experts and five non-experts each resected one lesion using DEIP-ESD and one using C-ESD. We evaluated the treatment outcomes and performed stratified analyses between the experts and non-experts. RESULTS: Dissection speed was significantly faster in DEIP-ESD than in C-ESD (13.3 mm2/min vs 28.5 mm2/min, P = 0.002). However, the total procedure time did not differ significantly between DEIP-ESD and C-ESD. In the stratified analyses, the dissection speed of non-experts was significantly faster in DEIP-ESD than in C-ESD (10.9 mm2/min vs 25.1 mm2/min, P = 0.016), while that of experts increased in DEIP-ESD but to a lesser extent (19.1 mm2/min vs 28.8 mm2/min, P = 0.1). The total procedure time did not differ between DEIP-ESD and C-ESD for both experts and non-experts. The self-completion rate of non-experts also increased in DEIP-ESD. Moreover, the number of muscularis propria injuries induced by non-experts was fewer in DEIP-ESD than in C-ESD. CONCLUSIONS: DEIP could facilitate colorectal ESD by improving dissection efficiency without increasing adverse events, especially when performed by non-experts.

Recurrent metastasis risk factors in esophageal cancer after salvage endoscopic resection for local failure following chemoradiotherapy.

OBJECTIVES: Although salvage endoscopic resection is an optimal treatment for local failure after chemoradiotherapy for esophageal squamous cell carcinoma, recurrent metastasis (lymph node and/or distant metastasis) after salvage endoscopic resection may occur with a certain degree of unavoidable frequency and is associated with a poor prognosis. However, the risk factors for recurrent metastasis are unclear. This study aimed to evaluate the risk factors for recurrent metastasis after salvage endoscopic resection. METHODS: Patients who underwent salvage endoscopic resection for local failure after chemoradiotherapy/radiotherapy were analyzed in this single-center, retrospective study. We evaluated the cumulative incidence rates of recurrent metastases, overall survival, and the risk factors for recurrent metastasis after salvage endoscopic resection. RESULTS: We analyzed 132 patients. The 5-year cumulative incidence rate of recurrent metastases after salvage endoscopic resection was 25.7%. The 5-year overall survival rates in all patients and in patients with recurrent metastasis were 66.8% and 22.5%, respectively. Local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy (subdistribution hazard ratio 2.34; P = 0.012) and the presence of lymphatic invasion in salvage endoscopic resection specimen (subdistribution hazard ratio 3.20; P = 0.002) were significant risk factors for recurrent metastasis. CONCLUSIONS: Patients with local failure pattern with a residual lesion after chemoradiotherapy/radiotherapy and presence of lymphatic invasion have a high risk for recurrent metastasis. Thus, appropriate surveillance for these patients should be considered.

Efficacy and safety of second photodynamic therapy for local failure after salvage photodynamic therapy for esophageal cancer.

OBJECTIVES: Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. METHODS: We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer, <3 cm in size, and <3/4 of the esophageal circumference; not suitable for salvage surgery; and absence of metastasis. Second PDT was avoided when lesions were apparently refractory to first PDT, e.g. persistence of submucosal tumor-like protruded component or rapid regrowth of tumor at the ulceration after first PDT. L-CR was defined as endoscopic disappearance of tumor and post-PDT ulcer and absence of cancer cells histologically. RESULTS: Among 82 patients who underwent first PDT, 27 underwent second PDT. The L-CR rates with first and second PDT were 63.0% and 40.7%, respectively. The 2-year overall survival rates after second PDT in patients with L-CR and local-nonCR were 79.5% and 40.5%, respectively. Five of 11 patients with L-CR survived without any recurrence. No grade ≥3 adverse events occurred. CONCLUSIONS: Second PDT demonstrated excellent safety and acceptable efficacy; therefore, it could be a useful treatment for local failure after first PDT.

Factors of technical difficulty in conventional and traction-assisted esophageal endoscopic submucosal dissection.

BACKGROUND: The traction assisted (TA) method has reduced the technical difficulty associated with esophageal endoscopic submucosal dissection (ESD). However, it is unclear which factors associated with difficulty have been improved by the TA-ESD method. We aimed to evaluate and compare difficulty factors between conventional and TA-ESD. METHODS: We retrospectively enrolled patients treated by ESD from Apr 2010 to Jun 2014 for the conventional ESD cohort and from Jan 2016 to Dec 2019 for the TA-ESD cohort. Difficult cases were defined as; (1) ≥ 120 min ESD procedure time, (2) intraoperative perforation, or (3) piecemeal resection. We explored and compared the factors associated with technical difficulty in each cohort. RESULTS: The conventional and TA-ESD cohorts included 285 (299 lesions) and 387 (421 lesions) patients, respectively. For difficult cases, the conventional and TA-ESD cohorts had 91 (30%) and 71 (17%) lesions, respectively. Multivariate logistic regression showed that ≥ 30 mm lesion length (odds ratio (OR) 6.85, 95% confidence interval (CI) 3.47-13.50), lower esophagus (OR 2.37, 95% Cl 1.34-4.21), > 1/2 circumference (OR 2.26, 95% CI 1.28-3.99), and left wall (OR 2.72, 95% CI 1.42-5.20) in the conventional ESD cohort, and ≥ 30 mm lesion length (21.30, 95% CI 4.75-95.30), lower esophagus (OR 3.05, 95% CI 1.52-6.13), and > 1/2 circumference (OR 6.40, 95% CI 3.06-13.40) in the TA-ESD cohort, were independently associated with technical difficulty. CONCLUSIONS: TA-ESD can reduce the difficulty in cases including lesions in the left wall; however, cases in the lower esophagus and large lesions were still difficult to simplify.

Long-term clinical outcomes of patients diagnosed with pT1a-muscularis mucosae with lymphovascular invasion or pT1b after endoscopic resection for cT1N0M0 esophageal squamous cell carcinoma.

BACKGROUND: Endoscopic resection (ER) is performed for early esophageal squamous cell carcinoma (ESCC) cases. Additional esophagectomy or chemoradiotherapy is recommended for non-curative resection (NCR) even with pathologically negative vertical margins (pVM0); however, their clinical outcomes remain unknown. We examined the long-term clinical outcomes of NCR for ESCCs according to additional treatments. METHODS: We retrospectively analyzed the data of patients who underwent ER for cT1N0M0 ESCC between 2009 and 2017 judged to have NCR, which defined when pathologically diagnosed as invading the submucosa (SM) or muscularis mucosae (MM) involving lymphovascular invasion (LVI), pVM0, and endoscopically judged as negative horizontal margin. Additional esophagectomy (involving three-field lymphadenectomy), chemoradiotherapy [mainly cisplatin and 5-fluorouracil with concurrent radiotherapy (41.4 Gy)], or observation was undertaken. Thereafter, computed tomography was performed every 6-12 months. The cumulative recurrence (CRR) and recurrence-free survival (RFS) rates were evaluated. RESULTS: Eighty-nine patients were included. Among them, 14 had pathologically diagnosed pMM with LVI; 9 and 6, and 32 and 28 patients had pSM1 and pSM2 without and with LVI. Twenty-one patients underwent observation, whereas 18 and 50 underwent esophagectomy and chemoradiotherapy. During the 60.6-month median follow-up period, nine patients had recurrence; among them, six patients had occurrence at > 4 years after ER. The 5-year CRR/RFS rates were 35.7%/48.1%, 13.4%/80.4%, and 0.0%/98.0% in the observation, esophagectomy, and chemoradiotherapy groups, respectively (observation vs. chemoradiotherapy; P < 0.001). CONCLUSIONS: Additional treatments showed better long-term outcomes than observation for patients with NCR. As recurrence may occur at > 4 years after ER, careful long-term follow-up examinations are needed.

Endoscopic resection combined with the Cryoballoon focal ablation system in the porcine normal esophagus: a preclinical study.

BACKGROUND: The Cryoballoon focal ablation system (CbFAS) for dysplastic Barrett's esophagus is simple, time-saving and has high therapeutic efficacy. This study aimed to evaluate the technical feasibility and tissue damage with combination therapy of endoscopic resection (ER) and CbFAS in porcine models. METHODS: Three pigs (A, B, and C) were included, and all ER procedures were performed by endoscopic mucosal resection using the Cap method (EMR). Combination therapy for each pig was performed as follows: (a) CbFAS was performed for a post-EMR mucosal defect for Pig A; (b) CbFAS for post-EMR scar for Pig B, and (c) EMR for post-CbFAS scar for Pig C. All pigs were euthanized at 32 days after the initial procedure, and the tissue damage was evaluated. RESULTS: All endoscopic procedures were followed as scheduled. None of the subjects experienced anorexia, rapid weight loss, bleeding, and perforation during the observation period. They were euthanized at 32 days after the initial endoscopic procedure. On histological assessment, there was little difference between the tissue that was treated with CbFAS alone and that treated with CbFAS in combination with ER. CONCLUSION: Combination therapy with ER and CbFAS can be technically feasible, and its outcome was not significantly different from CbFAS alone in terms of tissue damage.

Over 1000 nm Near-Infrared Multispectral Imaging System for Laparoscopic In Vivo Imaging.

In this study, a laparoscopic imaging device and a light source able to select wavelengths by bandpass filters were developed to perform multispectral imaging (MSI) using over 1000 nm near-infrared (OTN-NIR) on regions under a laparoscope. Subsequently, MSI (wavelengths: 1000-1400 nm) was performed using the built device on nine live mice before and after tumor implantation. The normal and tumor pixels captured within the mice were used as teaching data sets, and the tumor-implanted mice data were classified using a neural network applied following a leave-one-out cross-validation procedure. The system provided a specificity of 89.5%, a sensitivity of 53.5%, and an accuracy of 87.8% for subcutaneous tumor discrimination. Aggregated true-positive (TP) pixels were confirmed in all tumor-implanted mice, which indicated that the laparoscopic OTN-NIR MSI could potentially be applied in vivo for classifying target lesions such as cancer in deep tissues.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

BACKGROUND: Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. METHODS: We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. RESULTS: Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. CONCLUSIONS: The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients.

Enhanced tumor response to radiotherapy after PD-1 blockade in metastatic gastric cancer.

BACKGROUND: Immune checkpoint inhibitors may enhance the efficacy of radiotherapy (RT) in cancer treatment but the effect remains unknown in metastatic gastric cancer (mGC). This study aimed to compare the tumor shrinkage by palliative RT for mGC patients with or without previous exposure to anti-PD-1 therapy. METHODS: Data of 36 mGC patients who had received palliative RT from April 2013 to May 2019 were analyzed. Primary tumor responses were evaluated through a volumetric measurement-based method using computed tomography (CT) and endoscopic responses were evaluated in patients who underwent endoscopy before and after RT. Tumor microenvironment (TME) immune status was investigated by analyzing tumor-infiltrating lymphocytes by flow cytometry. RESULTS: Among 36 patients, 18 had previous exposure to anti-PD-1 before RT showing no significant differences in baseline characteristics with the other 18 patients without exposure to anti-PD-1 treatment. Tumor responses were observed in 28% (5/18) and none (0/18) in the anti-PD-1-exposed vs. naïve group, respectively (P = 0.045). Five out of eight patients in the anti-PD-1-exposed group, who underwent endoscopy after RT showed partial response, but none in the anti-PD-1-naïve patients showed response (P = 0.026). Increase in the CD8+ T cell/effector regulatory T cell ratio in TILs after anti-PD-1 therapy was noted in three responders to RT, but not in the other three non-responders. CONCLUSIONS: Prior exposure to anti-PD-1 therapy increases tumor response to RT. Immune profiling suggests that anti-PD-1 therapy may enhance the efficacy of RT by immunoactivation in the TME.

Endoscopic prediction of advanced histology in colorectal lesions sized <10 mm using the Japan Narrow-band imaging Expert Team classification.

BACKGROUND AND AIM: Endoscopic diagnosis of advanced histology in colorectal lesions sized <10 mm is essential for appropriate selection of resection methods. The Japan Narrow-band imaging Expert Team (JNET) classification has been recently validated for the evaluation of colorectal lesions. Our objective was to investigate the diagnostic value of the JNET classification for advanced histology in colorectal lesions sized <10 mm. METHODS: We enrolled 680 patients with 1472 colorectal lesions sized <10 mm diagnosed according to the JNET classification and who subsequently underwent endoscopic or surgical resection between January and December 2017. We retrospectively examined the relationship between the JNET findings and pathological histology. Multivariate analysis was carried out to assess the predictive power of the JNET findings and clinical characteristics of lesions. RESULTS: Advanced histology was present in 29 (2.0%) lesions. Advanced histology was absent in 68 lesions diagnosed as JNET type 1, whereas 1389 lesions diagnosed as JNET type 2A included 19 lesions of advanced histology (1.4%) with high-grade dysplasia alone. Eleven lesions diagnosed as JNET type 2B comprised eight lesions of advanced histology (72.7%) with four high-grade dysplasia and four submucosal invasive cancer, and two lesions diagnosed as JNET type 3 were submucosal invasive cancer. Multivariate analysis showed that JNET type 2B + 3 was a stronger predictive factor for advanced histology than other clinical risk factors. CONCLUSION: Narrow-band imaging with magnification according to the JNET classification may be a useful modality for identification of advanced histology in colorectal lesions sized <10 mm.

Human epidermal growth factor receptor 2-, epidermal growth factor receptor-, and mesenchymal epithelial transition factor-positive sites of gastric cancer using surgical samples.

BACKGROUND: Receptor tyrosine kinases (RTKs) play critical roles in gastric cancer (GC) progression and are potential targets for novel molecular-targeted agents or photo-immunotherapies. During patient selection, targeted biopsy is the first step. However, heterogeneous expression of RTKs based on the macroscopic appearance in GC has not been extensively addressed. Accordingly, in this study, we evaluated differences in RTK expression associated with macroscopic appearance in GC. METHODS: In total, 375 consecutive patients who had undergone gastrectomy at the National Cancer Center Hospital East and who had histologically proven adenocarcinoma, available archived tumor sample, and no history of chemotherapy were enrolled in this study. For these cases, tissue microarray (TMA) samples were examined using immunohistochemistry (IHC). Based on the results of IHC, cases were selected for detailed examination. We re-evaluated IHC scores in more than three tumor blocks per case and comparatively evaluated differences in IHC expression in RTKs between the mucosal portion (MuP) and invasive portion (InP). RESULTS: Human epidermal growth factor receptor 2 (HER2)-, epidermal growth factor receptor (EGFR)-, and mesenchymal epithelial transition factor (c-MET)-positive rates were 6, 9, and 20%, respectively. Twenty-two cases were then analyzed to assess differences in IHC expression levels in the same lesion. Concordance rates of positive staining of HER2, EGFR, and MET between MuP and whole tumor were 100, 40, and 56% and those with InP were 46, 100, and 56%. CONCLUSIONS: To avoid underestimating expression status, biopsies must be taken from MuP for HER2, InP for EGFR, and both proportions for c-MET.

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum ß-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan.

Objective evaluation of the visibility of colorectal lesions using eye tracking.

BACKGROUND AND AIM: To assess the visibility of colorectal lesions using blue laser imaging (BLI)-bright and linked-color imaging (LCI) with an eye-tracking system. METHODS: Eleven endoscopists evaluated 90 images of 30 colorectal lesions. The lesions were randomly selected. Three images of each lesion comprised white light imaging (WLI), BLI-bright, and LCI in the same position. Participants gazed at the images, and their eye movements were tracked by the eye tracker. We analyzed whether the participants could detect the lesion and how long they took to detect the lesion. We assessed the miss rate and detection time among the imaging modalities. RESULTS: One endoscopist was excluded, and 10 endoscopists were assessed. Overall, 12.6% of lesions were missed with WLI, 6.0% with BLI-bright, and 4.3% with LCI; the miss rate of BLI-bright and LCI was significantly lower than that of WLI (P < 0.01), with no significant difference between the former modalities (P = 0.54). Mean (± SD) detection times were 1.58 ± 1.60 s for WLI, 1.01 ± 1.21 s for BLI-bright, and 1.10 ± 1.16 s for LCI. Detection time for BLI-bright and LCI was significantly shorter than that for WLI (P < 0.0001), with no significant difference between the former modalities (P = 0.34). Regarding the miss rate and detection time between the expert and the non-experts, there was a significant difference with WLI but not with BLI-bright and LCI. CONCLUSION: Blue laser imaging-bright and LCI improved the detection of colorectal lesions compared with WLI using an eye-tracking system.