Functional Peptide-Modified Liposomes for siRNA Delivery to Rat Retinal Pigment Epithelium Cells: Effect of Peptide Sequences.

Most retinal diseases involve the degeneration of choroidal retinal pigment epithelial (RPE) cells. Because of a blood-retina barrier (tight junction formation), RPE cells restrict the entry of hydrophilic macromolecules (e.g., small interfering RNA (siRNA)) through blood stream and eye drops. A cytoplasm-responsive stearylated (STR) peptide, STR-CH2R4H2C (CH2R4) enables stable siRNA complexation, cell permeation, and intracellular dynamics control. We previously demonstrated how CH2R4-modified liposomes promoted siRNA efficacy. We investigated the influence of amino acid sequences of functional peptides on cellular uptake pathways, siRNA transfection efficacy, and the permeation of peptide-modified liposomes in rat RPE-J cells. Four STR-peptides, consisting of arginine (R), cysteine (C), histidine (H), lysine (K) or serine (S), were designed based on CH2R4. We prepared siRNA-loaded, peptide-modified cationic liposomes (CH2R4-, CH2K4-, CH2S4-, SH2R4-, and SH2S4-lipoplexes). CH2R4-, CH2K4-, and SH2R4-lipoplexes induced cellular uptake by macropinocytosis by activating cytoskeletal F-actin, possibly due to cationic amino acids (arginine, lysine). SH2R4-lipoplexes were trapped in endosomes, whereas CH2R4- and CH2K4-lipoplexes enhanced endosomal siRNA release suggesting cysteine contributes to endosomal escape. Although cationic liposome-based, CH2S4- and SH2S4-lipoplexes (not including arginine and lysine) showed lower siRNA transfection efficiency. This difference may be because siRNAs were retained on both peptide moieties and cationic liposomes in CH2R4-, CH2K4- and SH2R4-lipoplexes, whereas in CH2S4- and SH2S4-lipoplexes, siRNAs were loaded to the cationic liposomes, but not on peptides. In three-dimensional spheroids, CH2R4- and CH2K4-modified liposomes promoted permeation through tight junctions. Thus, cationic amino acids and cysteine within peptide sequences of CH2R4 could be effective for siRNA delivery to the retina using functional peptide-modified liposomes.

A case of non-neutropenic invasive pulmonary aspergillosis under immune checkpoint inhibitor therapy for malignant melanoma.

The patient was a 70-year-old man with diabetes mellitus, alcoholic liver disease and bronchial asthma treated with corticosteroid and long-acting ß-agonist inhalants. He had also been treated with nivolumab for advanced malignant melanoma for two years with a partial response. He presented to our department with intractable cough, which was attributed to uncontrolled bronchial asthma. Two weeks later, he presented with a high fever and worsened cough. He was diagnosed with bacterial pneumonia based on severe inflammation revealed by laboratory tests and right upper lung consolidation on chest radiography. Antibiotics via either oral or parenteral administration were ineffective and no pathogen was detected in sputum or blood cultures. Based on the air-crescent sign observed on chest computed tomography and a diffuse pseudomembranous lesion on the airway epithelium that was observed via bronchoscopy along with positive serum Aspergillus antigen, a clinical diagnosis of invasive pulmonary aspergillosis (IPA) was made and liposomal amphotericin B was initiated. Three days later, the patient developed massive hemoptysis, and he died of respiratory failure. Later, aspergillus-like mycelia were observed in the pathology of bronchial biopsy, supporting the clinical diagnosis of IPA. Although the use of immune checkpoint inhibitors has been reported to be beneficial for patients with some infectious diseases, it does not seem to be the case for patients with other infectious diseases including our patient.

Dramatic response to alectinib in an ALK-positive LCNEC patient with a poor performance status: A case report.

The echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene, a driver mutation in lung carcinoma, is fairly common in lung adenocarcinoma but rare in large cell neuroendocrine carcinoma (LCNEC). Here we report a case of stage IV LCNEC positive for this fusion gene in a patient with a poor performance status (PS) who was effectively treated with alectinib. The patient was a 72-year-old non-smoking man diagnosed as LCNEC with multiple metastases. Because of his poor PS, cytotoxic chemotherapy was not indicated, but he was later found to be positive for the ALK fusion gene and treated with alectinib as first-line therapy. One month later, the tumour had shrunk remarkably, and the therapeutic effect was rated as a partial response. The PS also improved from 4 to 1. Investigating actionable driver mutations seems worth doing for advanced LCNEC, especially if the patient's PS is poor.

Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

Background and study aims A white opaque substance (WOS) has been observed in the epithelia of gastric, duodenal, and colorectal epithelial adenomas and carcinomas, using magnifying endoscopy (ME). The WOS has been reported to be derived from a dense accumulation of minute lipid droplets in the epithelium. This study aimed to investigate whether the WOS in colorectal hyperplastic polyps was derived from lipid droplets accumulated in the epithelium, as observed in the case of gastric, duodenal, and colorectal epithelial neoplasms. Patients and methods We analyzed 30 consecutive patients who were positive for the WOS, as visualized in colorectal hyperplastic polyps by ME with narrow-band imaging and 30 consecutive patients who were negative for the WOS. Biopsy specimens obtained from the polyps were immunostained with anti-adipophilin antibody to determine the correlation between the presence of the WOS and that of lipid droplets in the epithelium. Results In all patients, the epithelial cells were histologically positive for adipophilin. However, the area of adipophilin-positive epithelial cells in the WOS-positive group was significantly larger than that in the WOS-negative group ( P  < 0.001). The density of the WOS was strongly and positively correlated with the area of adipophilin-positive cells. Conclusions This study reveals that the WOS visualized in the superficial layers of colorectal hyperplastic polyps is produced by a dense accumulation of minute lipid droplets in the epithelia of the polyps.

Erratum: Nature of a white opaque substance visualized by magnifying endoscopy in colorectal hyperplastic polyps.

[This corrects the article DOI: 10.1055/a-1452-9669.].

[A Case of Hepatocellular Carcinoma Complicated by Liver Metastasis of Colon Cancer during the Course of Treatment].

A 72‒year‒old man with hepatocellular carcinoma(HCC)was treated with transarterial chemoembolization(TACE)and radiofrequency ablation(RFA). Six months after RFA, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd‒ EOB‒DTPA)‒enhanced magnetic resonance imaging(MRI)revealed multiple metastatic recurrences in the liver. TACE was performed for the recurrent HCC. However, the treatment response on the Gd‒EOB‒DTPA‒enhanced MRI showed that the lesions had advanced and that the liver metastatic nodules had ring‒shaped contrast effects. We suspected metastatic liver cancer based on the MRI findings and performed colonoscopy. Finally, we diagnosed the patient with multiple hepatic metastases of sigmoid colon cancer based on the results of the endoscopic colon biopsy and percutaneous liver tumor biopsy. In conclusion, we had a teachable case of the treatment of HCC.

Significant therapeutic effectiveness of durvalumab after chemoradiotherapy for a patient with post-operative recurrent pulmonary pleomorphic carcinoma.

Pulmonary pleomorphic carcinoma (PPC) is a poorly differentiated non-small cell lung cancer. Because of its rarity, no standard therapy has been established for advanced disease. We herein report on a 62-year-old man with recurrent post-operative PPC, for whom durvalumab after chemoradiotherapy was effective. He was referred to our hospital because of an abnormal shadow in the right upper lung on chest X-ray. After surgical resection was performed, the imaging and histopathological findings revealed PPC (T4N0M0, stage IIIA) with elevated expression of programmed cell death-ligand 1 (PD-L1). A metastasis was found in the left hemithorax 22 months later, and chemoradiotherapy consisting of 60 Gy of radiation and cisplatin plus tegafur/gimeracil/oteracil potassium was administered. Durvalumab was then begun as consolidation therapy. The efficacy of the treatments has continued for longer than 10 months. This case suggests that multidisciplinary treatment with chemoradiotherapy and consolidation immunotherapy may improve the prognosis of locally advanced PPC.

White Opaque Substance, a New Optical Marker on Magnifying Endoscopy: Usefulness in Diagnosing Colorectal Epithelial Neoplasms.

BACKGROUND/AIMS: A white substance that is opaque to endoscopic light is sometimes observed in the epithelium during narrowband imaging with magnifying endoscopy of gastric or colorectal epithelial neoplasms. This prospective observational study aimed to determine whether the morphology of the white opaque substance (WOS) allows differential diagnosis between colorectal adenoma and carcinoma. METHODS: A consecutive series of patients with colorectal adenomas or early carcinomas who underwent endoscopic resection or surgical excision were studied. The morphology of the WOS was determined based on endoscopic images before the histopathological diagnosis was performed. The primary outcome was the diagnostic performance of an irregular WOS as a marker of colorectal carcinoma. RESULTS: The study analyzed 125 lesions. A total of 33 lesions showed an irregular WOS, and 92 lesions showed a regular WOS. Among the 33 lesions found to show an irregular WOS, 30 were carcinomas. Among the 92 lesions showing a regular WOS, 79 were adenomas. With irregular WOS as a marker of carcinoma, the diagnostic accuracy was 87%, sensitivity was 91%, and specificity was 86%. CONCLUSION: This study demonstrated the potential usefulness of the morphology of the WOS as a marker for the differential diagnosis between adenoma and carcinoma in cases of colorectal epithelial neoplasms.

Myositis induced by durvalumab in a patient with non-small cell lung cancer: A case report.

Immune checkpoint inhibition is associated with a broad spectrum of immune toxicities referred to as immune-related adverse events (irAEs). Myositis is known to be a potentially fatal irAE. Here, we report a case of immune-related myositis after the administration of durvalumab. A 60-year-old man with stage IIIA lung adenocarcinoma was treated with durvalumab after concurrent chemoradiation therapy. After the third dose of durvalumab, his serum CK level was elevated, and soon thereafter myalgia of the proximal muscles and blepharoptosis were observed. We diagnosed immune-related myositis based on the results of pathological examination and initiated systemic corticosteroid therapy. His symptoms then improved and the serum CK level immediately dropped to within a normal range. Clinicians should be aware of possible myositis during the early phase of durvalumab therapy.

Microsatellite Instability-high Intrahepatic Cholangiocarcinoma with Portal Vein Tumor Thrombosis Successfully Treated with Pembrolizumab.

A 60-year-old man presented with postoperative recurrence of intrahepatic cholangiocarcinoma with right portal vein tumor thrombosis (PVTT). After failure of standard chemotherapy, a liver biopsy showed that his microsatellite instability (MSI) status was high. Treatment with the immune checkpoint inhibitor (ICI) pembrolizumab was commenced, which resulted in a partial response and resolution of the PVTT. There were no significant immune-related adverse events. According to recently published reports, the frequency of MSI-high biliary tract cancer (BTC) is about 0-2.1%, which is extremely rare. However, ICIs may be effective in patients with MSI-high BTC, such as the present patient.

Therapeutic Potential of LNP-Mediated Delivery of miR-634 for Cancer Therapy.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that negatively regulate gene expression by interfering with the translation or stability of target transcripts. Some tumor-suppressive miRNAs can concurrently target multiple cancer-promoting genes and may be useful as therapeutic anticancer agents. However, the development of drug delivery systems is critical for the implementation of miRNA-based therapeutics. We have previously demonstrated that the enforced expression of miR-634 effectively induces apoptosis by concurrently and directly targeting genes associated with mitochondrial homeostasis, antiapoptosis signaling, antioxidant ability, and autophagy in cancer cells. In the current study, we validated the therapeutic potential of lipid nanoparticle (LNP)-mediated delivery of miR-634 for cancer therapy. We confirmed the ability of enforced expression of miR-634 to induce apoptosis in various cancer cell lines, including pancreatic cancer cells. Intravenous administration of LNPs harboring miR-634 significantly reduced the xenograft tumor growth of BxPC-3 pancreatic cancer cells in mice. These findings suggest that LNP-mediated delivery of miR-634 can potentially be used for cancer therapy.

Comparison Between Linked Color Imaging and Blue Laser Imaging for Improving the Visibility of Flat Colorectal Polyps: A Multicenter Pilot Study.

INTRODUCTION: Linked color imaging (LCI) and blue laser imaging-bright (BLI-b) improve the visibility of gastrointestinal lesions. In this multicenter study, we compared the effects of LCI and BLI-b on the visibility of flat polyps with visibility scores and color difference (CD) values, including fast-withdrawal and large-monitor observation. METHODS: We recorded 120 videos of 40 consecutive flat polyps (2-20 mm), adenoma, and sessile serrated adenoma and polyp (SSA/P), using white light imaging (WLI), BLI-b, and LCI from July 2017 to December 2017. All videos were evaluated by eight endoscopists according to a published polyp visibility score of 4 (excellent) to 1 (poor). Additionally, 1.5 ×faster and 1.7 ×sized videos were evaluated. Moreover, we calculated the CD values for each polyp in three modes. RESULTS: The mean LCI scores (3.1 ± 0.9) were significantly higher than the WLI scores (2.5 ± 1.0, p < 0.001) but not significantly higher than the BLI-b scores (3.0 ± 1.0). The scores of faster videos on LCI (3.0 ± 1.1) were significantly higher than WLI (2.0 ± 1.0, p < 0.001) and BLI-b (2.8 ± 1.1, p = 0.03). The scores of larger-sized videos on LCI were not significantly higher than those of WLI or BLI-b. The CD value of LCI (18.0 ± 7.7) was higher than that of WLI (11.7 ± 7.0, p < 0.001), but was not significantly higher than that of BLI-b (16.6 ± 9.6). The CD value of LCI was significantly higher than that of BLI-b for adenoma, but the CD value of BLI-b was significantly higher than that of LCI for SSA/P. CONCLUSIONS: The superiority of LCI to BLI-b was proven for the visibility of adenoma and fast observation.

Kinetics of cytokine mRNA and protein expression by plastic adherent cells in the thymus after split-dose irradiation.

Whole body irradiation causes significant apoptosis in various tissues such as the thymus. If apoptotic cells outnumber the phagocytic capacity of macrophages, apoptosis becomes secondary necrosis, inducing inflammatory cytokine expression in macrophages. Radiation also induces thymic lymphomas in C57BL/6 mice after four consecutive irradiations with 1.6 Gy X-rays with nearly 100% incidence. Since cancer development is modulated by a microenvironment involving macrophages, we examined the kinetics of thymocyte number and plastic adherent cell number in the thymus as well as cytokine mRNA expression by plastic adherent cells in the thymus after split-dose irradiation. Upon split-dose irradiation, thymocyte number changed dramatically, whereas plastic adherent cell number did not. Among cytokine mRNAs tested, IL-1ß, IL-11 and IL-12p40 mRNAs were up regulated 2 days after the 1st and 2nd, 3rd and 4th, and 2nd and 3rd irradiations, respectively. On the other hand, TNF-α mRNA was up regulated 2 days after the 3rd irradiation and 2 weeks after the 4th irradiation. The level of IL-11 protein was also increased 2 days after 3rd and 4th irradiations. These results suggest that, upon split-dose irradiation, macrophages in the thymus produce various cytokines in a time-dependent manner, thereby contributing to induction of thymic lymphomas.

ß-Hydroxy-ß-methyl Butyrate/L-Arginine/L-Glutamine Supplementation for Preventing Hand-Foot Skin Reaction in Sorafenib for Advanced Hepatocellular Carcinoma.

BACKGROUND/AIM: Sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a notorious side-effect of this therapy. This study evaluated prophylactic benefits of an oral nutritional supplement (ONS) on sorafenib-associated HFSR in advanced HCC. PATIENTS AND METHODS: This was a prospective, single-center, open-label trial arm using combined ONS and sorafenib in patients with unresectable HCC from August 2014 to February 2018. Control patients received sorafenib without ONS from 2011 to 2014. From September 2014, prophylactic ONS containing ß-hydroxy-ß-methylbutyrate (HMB), L-arginine, and L-glutamine was given. Sorafenib dosage was 400 mg/day for both groups. RESULTS: Each group comprised 22 men and three women. Age, sex, Child-Pugh score, and clinical stage excluding IV-B did not significantly differ between the groups. HFSR occurred after 2 weeks: 15/25 patients in the control group (60%; HFSR grade 1: 6, grade 2: 7, grade 3: 2) vs. 8/25 in the ONS group (32%; HFSR grade 1: 4, grade 2: 4, grade 3: 0; p=0.047, Pearson's Chi-square test). CONCLUSION: Prophylactic HMB, L-arginine and L-glutamine supplementation effectively prevented sorafenib-associated HFSR in patients with advanced HCC.

Risk factors for severity of colonic diverticular hemorrhage.

BACKGROUND/AIMS: Colonic diverticular hemorrhage (DH) was a rare disease until the 1990s, and its incidence has increased rapidly since 2000 in Japan. In recent years, colonic DH has been the most frequent cause of lower gastrointestinal bleeding (LGIB). Nearly all cases of DH are mild, with the bleeding often stopping spontaneously. Some cases, however, require surgery or arterial embolization. In this study, using a cohort at Fukuoka University Chikushi Hospital, we investigated factors associated with severe colonic DH. METHODS: Among patients with LGIB who underwent colonoscopy at our hospital between 1995 and 2013, DH was identified in 273 patients. Among them, 62 patients (22.7%) were defined as having severe colonic DH according to recurrence of bleeding in a short period, and/or the necessity of transfusion, arterial embolization, or surgery. We then evaluated risk factors for severe DH among DH patients in this retrospective cohort. RESULTS: Among the 273 patients with DH, use of non-steroidal anti-inflammatory drugs (NSAIDs) (odds ratio [OR], 2.801; 95% confidence interval [CI], 1.164-6.742), Charlson Risk Index (CRI) ≥2 (OR, 3.336; 95% CI, 1.154-7.353), right-sided colonic DH (OR, 3.873; 95% CI, 1.554-9.653), and symptoms of cerebral hypoperfusion (such as light-headedness, dizziness, or syncope) (OR, 2.926; 95% CI, 1.310-6.535) showed an increased risk of severe DH even after controlling for other factors. CONCLUSIONS: Severe DH occurred in 23% of DH patients, and NSAID use, CRI ≥2, right-sided colonic DH, and symptoms of cerebral hypoperfusion are suggested to be predictors of severe DH.

A case of drug induced lung injury caused by levofloxacin eye drops.

A 78 year-old man, who received levofloxacin eye drops as a perioperative prophylactic antibacterial agent for cataract surgery, developed pyrexia and dyspnea, followed by respiratory failure. He was diagnosed as drug-induced lung injury due to levofloxacin, and the symptoms improved after the administration of corticosteroids and discontinuation of levofloxacin eye drops. The incidence of levofloxacin-induced lung injury is rare for its frequent prescription. Moreover, eye drops of it has never been reported to cause lung injury. We should be aware of eye drops as a causative dosage forms of drug-induced lung injury.

Simulation of Stimuli-Responsive and Stoichiometrically Controlled Release Rate of Doxorubicin from Liposomes in Tumor Interstitial Fluid.

PURPOSE: To simulate the stimuli-responsive and stoichiometrically controlled doxorubicin (DOX) release from liposomes in in vivo tumor interstitial fluid (TIF), the effect of ammonia concentration and pH on the DOX release from liposomes in human plasma at 37°C was quantitatively evaluated in vitro and the release rate was calculated as a function of ammonia concentration and pH. METHODS: Human plasma samples spiked with DOX-loaded PEGylated liposomes (PLD) or Doxil®, containing ammonia (0.3-50 mM) at different pH values, were incubated at 37°C for 24 h. After incubation, the concentration of encapsulated DOX in the samples was determined by validated solid-phase extraction (SPE)-SPE-high performance liquid chromatography. RESULTS: Accelerated DOX release (%) from liposomes was observed as the increase of ammonia concentration and pH of the matrix, and the decrease of encapsulated DOX concentration. The release rate was expressed as a function of the ammonia concentration and pH by using Henderson-Hasselbalch equation. CONCLUSIONS: The DOX release from PLD in TIF was expressed as a function ammonia concentration and pH at various DOX concentrations. Further, it was found that the DOX release from liposomes in a simulated TIF was more than 15 times higher than in normal plasma.

Validity of conventional endoscopy using "non-extension sign" for optical diagnosis of colorectal deep submucosal invasive cancer.

BACKGROUND AND STUDY AIMS: The non-extension sign relates to a localized increase in thickness and rigidity due to deep submucosal invasive (SM-d: depth of 1000 µm or more) cancer. The present study aimed to evaluate the efficacy of the non-extension sign in assessing the optical diagnosis of colorectal SM-d cancer. PATIENTS AND METHODS: We retrospectively analyzed 309 patients with 315 early colorectal cancers that had been endoscopically or surgically resected. The non-extension sign was judged from chromoendoscopy (CE) using conventional white-light imaging with indigo carmine, and is taken to be positive when any one of the findings of rigidity of a circular arc, trapezoid elevation, or converging mucosal folds are seen. We assessed comparing the accuracy of CE, magnifying chromoendoscopy (M-CE), and magnifying narrow-band imaging (M-NBI) for the optical diagnosis of colorectal SM-d cancer. RESULTS: Sensitivity, specificity, and accuracy for the diagnosis of SM-d cancer were 66.0 %, 95.8 %, and 86.3 % for CE; 80 %, 90.7 %, and 87.3 % for M-CE; and 65.0 %, 94.4 %, and 85.1 % for M-NBI, respectively. The specificity of CE was significantly higher than that of M-CE ( P  = 0.034). The sensitivity of M-CE was significantly higher than that of CE ( P  = 0.026). In a comparison of positive and negative groups for the non-extension sign in SM-d cancer, SM invasion was significantly deeper in the positive group than in the negative group (3012.5 µm vs 2002.4 µm, respectively; P  < 0.0001) and the rate of lymphovascular invasion was significantly higher in the positive group than in the negative group (63.6 % vs 41.2 %, respectively; P  = 0.032). CONCLUSIONS: The non-extension sign offers high diagnostic specificity for SM-d cancer, and surgery should be considered in patients with a positive non-extension sign.

Association between Skeletal Muscle Depletion and Sorafenib Treatment in Male Patients with Hepatocellular Carcinoma: A Retrospective Cohort Study.

The effect of skeletal muscle mass (SMM) on the outcomes of sorafenib treatment for hepatocellular carcinoma (HCC) has not been established. We measured the SMM in HCC patients treated with sorafenib, evaluated the patients' survival, and evaluated the association between skeletal muscle depletion and sorafenib treatment. Of the 97 HCC patients treated with sorafenib at our institution in the period from July 2009 to February 2015, our study included 69 patients (51 males, 18 females) who had received sorafenib for ≥ 8 weeks and whose follow-up data were available. SMM was calculated from computed tomography images at the mid-L3 level (cm2) and normalized to height (m2) to yield the L3 skeletal muscle index (L3-SMI, cm2/m2). The median L3-SMI value was higher in the males (43 cm2/m2) compared to the females (36 cm2/m2). In the males only, the multivariate Cox regression identified an L3-SMI <43 cm2/m2 as independently associated with higher mortality compared to an L3-SMI ≥43 cm2/m2 (hazard ratio 2.315, 95% confidence interval: 1.125-4.765, p=0.023). Skeletal muscle depletion is a factor predicting poor prognosis for male patients with advanced HCC treated with sorafenib.

Detectability of colorectal neoplastic lesions using a novel endoscopic system with blue laser imaging: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Most studies have not reported an improvement in the detection of adenomas with the use of image-enhanced colonoscopy methods, possibly because of the darkness of the images. To overcome this limitation, a new-generation endoscopic system has been developed. This system has 2 blue-laser imaging (BLI) observation modes. The BLI observation was set to BLI-bright mode to detect lesions. We aimed to evaluate the efficacy of BLI in detecting lesions. METHODS: This study was designed as a randomized controlled trial with participants from 8 institutions. We enrolled patients aged ≥40 years. The participants were randomly assigned to 2 groups: observation by using white-light imaging (WLI) with a conventional xenon light source (WLI group) or observation by using BLI-bright mode with a laser light source (BLI group). All of the detected lesions were resected or had a biopsy taken for histopathologic analysis. The primary outcome was the mean number of adenomas per patient (MAP) that were detected per procedure. RESULTS: The WLI and BLI groups consisted of 474 and 489 patients, respectively. The MAP was significantly higher in the BLI group than in the WLI group (mean ± standard deviation [SD] WLI 1.01 ± 1.36, BLI 1.27 ± 1.73; P = .008). Adenoma detection rate in the BLI group was not significantly higher than in the WLI group. Observation times differed significantly, with BLI (9.48 minutes) being longer than WLI (8.42; P < .001). The mean (± SD) number of polyps per patient was significantly higher in the BLI group compared with the WLI group (WLI 1.43 ± 1.64, BLI 1.84 ± 2.09; P = .001). CONCLUSIONS: A newly developed system that uses BLI improves the detection of adenomatous lesions compared with WLI. (Clinical trial registration number: UMIN 000014555.).