Usefulness of a target sample check illuminator in the detection of target specimens in endoscopic ultrasound-guided fine-needle biopsy samples: Multicenter prospective study.

OBJECTIVES: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) uses a thin needle, rendering unclear whether the collected sample contains pathological evidence. We examined the usefulness of our target sample check illuminator (TSCI) through a multicenter prospective trial. METHODS: We included 52 consecutive patients. After assessing EUS-FNB samples by conventional (visual observation) and TSCI methods, we evaluated consistency with the histopathological diagnosis. We compared the target sample confirmation rate between conventional and TSCI methods and evaluated the diagnostic ability separately. RESULTS: Comparison between the conventional and TSCI methods revealed the following: (i) for all cases: sensitivity, 51.0% (25/49) vs. 95.9% (47/49) (P = 0.001); specificity, 100% (3/3) vs. 66.7% (2/3); positive predictive value (PPV), 100% (25/25) vs. 97.9% (47/48); and negative predictive value (NPV), 11.1% (3/27) vs. 50.0% (2/4) (P = 0.002); (ii) for pancreatic masses: sensitivity, 28.0% (7/25) vs. 96.0% (24/25) (P < 0.001); specificity, 100% (2/2) vs. 100% (2/2); PPV, 100% (7/7) vs. 100% (24/24); and NPV, 10.0% (2/20) vs. 66.7% (2/3) (P < 0.001) (the TSCI method showed significantly better sensitivity and NPV than the conventional method); and (iii) for lymph node tumors: sensitivity, 75.0% (18/24) vs. 95.8% (23/24) (P = 0.025); specificity, 100% (1/1) vs. 0% (0/1); PPV, 100% (18/18) vs. 95.8% (23/24); and NPV, 14.3% (1/7) vs. 0% (0/1). CONCLUSIONS: The TSCI improved the sensitivity, NPV, and accuracy of target sample confirmation for pancreatic mass EUS-FNB. Although the proportion of samples not including a target region was quite low, which could strongly influence our results, the TSCI method can be used in EUS-FNB when rapid on-site evaluation cannot be performed. (A multicenter prospective study for the utility of a target sample check illuminator, Clinical Trial ID: UMIN000023349).

Efficacy and safety of pancreatic juice cytology by using synthetic secretin in the diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND AND AIM: Pancreatic ductal adenocarcinoma (PDAC) is difficult to detect in its early stages with the poorest prognosis of all cancers. To improve the prognosis, a precise diagnosis is needed when we suspect PDAC. Although endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a widely accepted modality for the diagnosis of PDAC, its sensitivity is 85-89%, and approximately 10% of PDAC cases cannot be diagnosed. The main causes that interrupt the diagnosis of PDAC by using EUS-FNA are tumor size, presence of a vessel or the main pancreatic duct along the puncture route, and difficulty in withdrawing anticoagulant. Pancreatic juice cytology (PJC), the sensitivity of which is 33.3-65.8%, is a method for the diagnosis of PDAC cases in which carrying out of EUS-FNA is difficult. To diagnose PDAC appropriately, we need to improve the diagnostic ability of PJC. METHODS: We examined PJC using synthetic secretin for 138 cases of pancreatic tumor and pancreatic non-cancerous diseases. RESULTS: Sensitivity of PJC improved from 50.9% to 74.0% as a result of synthetic secretin loading, and 13 PDAC cases that had not been able to be diagnosed with EUS-FNA could be diagnosed pathologically by PJC. Although there were 12 patients with mild pancreatitis (8.7%) as a complication, all were relieved with conservative treatment. CONCLUSION: Adding synthetic secretin to PJC is useful for cases in which it is difficult to carry out EUS-FNA for PDAC.

Cytokine Profile in Predicting the Effectiveness of Advanced Therapy for Ulcerative Colitis: A Narrative Review.

Cytokine-targeted therapies have shown efficacy in treating patients with ulcerative colitis (UC), but responses to these advanced therapies can vary. This variability may be due to differences in cytokine profiles among patients with UC. While the etiology of UC is not fully understood, abnormalities of the cytokine profiles are deeply involved in its pathophysiology. Therefore, an approach focused on the cytokine profile of individual patients with UC is ideal. Recent studies have demonstrated that molecular analysis of cytokine profiles in UC can predict response to each advanced therapy. This narrative review summarizes the molecules involved in the efficacy of various advanced therapies for UC. Understanding these associations may be helpful in selecting optimal therapeutic agents.

The Potential of Narrow-Band Imaging as a Novel Light Source for Photodynamic Therapy for Superficial Cancers via Endoscopes.

Background: Photodynamic therapy (PDT) has advanced through the utilization of photosensitizers and specific-wavelength light (≥ 600 nm). However, the widespread adoption of PDT is still impeded by high equipment costs and stringent laser safety requirements. Porphyrins, crucial in PDT, have another absorbance peak of blue light (λ = 380 - 500 nm). This peak corresponds to the wavelength of narrow-band imaging (NBI) (λ = 390 - 445 nm), an image-enhancement technology integrated into endoscopes by Olympus Medical Systems. The study aimed to investigate the potential of widely adopted NBI as a PDT light source for superficial cancers via endoscopes. Methods: Esophageal and biliary cancers were selected for investigation. Human esophageal cancer cell lines (KYSE30, KYSE70, KYSE170) and cholangiocarcinoma cell lines (HuCCT-1, KKU-213) were subjected to verteporfin-mediated PDT under NBI light (λ = 390 - 445 nm). Assessments included spectrometry, crystal violet staining, and fluorescein imaging of singlet oxygen generation and apoptosis. Results: Verteporfin exhibited a peak (λ = 436 nm) consistent with the NBI spectrum, suggesting compatibility with NBI light. NBI light significantly inhibited the growth of esophageal and biliary cancer cells. The half-maximum effective concentration (EC50) values (5 J/cm2) for KYSE30, KYSE70, KYSE170, HuCCT-1, and KKU-213 were calculated as 2.78 ± 0.37µM, 1.76 ± 1.20 µM, 0.77 ± 0.16 µM, 0.65 ± 0.18 µM, and 0.32 ± 0.04 µM, respectively. Verteporfin accumulation in mitochondria, coupled with singlet oxygen generation and observed apoptotic changes, suggests effective PDT under NBI light. Conclusions: NBI is a promising PDT light source for superficial cancers via endoscopes.

Docking Proteins Upregulate IL-1ß Expression in Lower Esophageal Sphincter Muscle in Esophageal Achalasia.

Background/Objectives: Esophageal achalasia is an archetypal esophageal motility disorder characterized by abnormal peristalsis of the esophageal body and impaired lower esophageal sphincter (LES) relaxation. Methods: In this study, the mRNA expression of docking proteins 1 and 2 (DOK1 and DOK2, respectively) were analyzed and the mechanisms underlying achalasia onset were investigated. Results:DOK1 and DOK2 mRNA levels significantly increased in the LES of patients with achalasia. Moreover, significant correlations were observed between IL-1ß and DOK1, IL-1ß and DOK2, ATG16L1 and DOK1, and HSV1-miR-H1-3p and DOK2 expression levels. However, a correlation between ATG16L1 and DOK2 or between HSV-miR-H1-3p and DOK1 expression was not observed. In addition, a positive correlation was observed between patient age and DOK1 expression. Microarray analysis revealed a significant decrease in the expression of hsa-miR-377-3p and miR-376a-3p in the LES muscle of patients with achalasia. Conclusions: These miRNAs possessed sequences targeting DOK. The upregulation of DOK1 and DOK2 expression induces IL-1ß expression in the LES of achalasia patients, which may contribute to the development of esophageal motility disorder.

Acceptability, Safety, and Feasibility of Transnasal and Peroral Ultrathin Endoscopy Using GAGLESS Mouthpieces: A Prospective Randomized Trial.

BACKGROUND/AIM: Esophagogastroduodenoscopy (EGD) is an effective screening method for early detection of gastric cancer. The GAGLESS mouthpiece has a structure that widens the pharyngeal cavity and suppresses the pharyngeal reflex. This study aimed to investigate the acceptability, safety, and feasibility of transnasal and peroral ultrathin endoscopy using GAGLESS mouthpieces (Clinical Trial Number: UMIN000036922). PATIENTS AND METHODS: This study was a multicenter, prospective, randomized, open-label trial performed using a questionnaire. The study included 101 consecutive patients who visited the participating medical institutions between June 2019 and March 2022 (median age=47 years, range=24-87 years; all male). Patients aged ≥20 years at the time of consent acquisition who were the first to undergo EGD were included in the study. The primary endpoint was the degree of distress during EGD, as determined using a visual analog scale (VAS). RESULTS: The VAS score during endoscopic passage through the pharynx was significantly better in the transnasal endoscopy group than in the oral endoscopy group (2.420 vs. 4.092, p=0.001). There was no significant difference in the VAS scores between the two groups during anesthesia or throughout the examination. Compared with nasal endoscopy, oral endoscopy with a GAGLESS mouthpiece did not reduce the VAS score but did significantly improve gastric visibility. CONCLUSION: For patients in whom there was difficulty in inserting a nasal endoscope, using a GAGLESS mouthpiece rather than a conventional mouthpiece may be more useful in reducing pain.

Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis.

Background: Endoscopic healing (EH) is the long-term therapeutic goal for ulcerative colitis (UC). Since repeated colonoscopies are inconvenient and invasive, a surrogate biomarker for endoscopic activity is needed. Activin A is one of the transforming growth factor-ß superfamily of proteins and has been shown to be associated with intestinal inflammation. Methods: This single-center observational study included 27 Japanese patients with UC in clinical remission who underwent colonoscopy and blood sampling. We investigated the correlations between laboratory parameters, including serum activin A levels, and endoscopic activity, classified by the Mayo endoscopic subscore (MES) in these patients. Results: This study included 15 males and 12 females. The median age was 44.0 years. In terms of endoscopic activity, five patients were diagnosed with MES 0, 14 patients with MES 1, seven patients with MES 2, and one patient with MES 3. The median serum activin level was 134.8 pg/mL (interquartile range (IQR), 105.3 - 188.1). Serum activin A levels were significantly correlated with the MES (Spearman's rank correlation coefficient r = 0.591, P = 0.001), which was better than that of C-reactive protein (CRP) (r = 0.487, P = 0.010). In the comparison between the EH group (MES 0) and non-EH group (MES 1-3), patients without EH had significantly higher serum activin A levels (Mann-Whitney U test, P = 0.047). A cutoff value of 133.6 pg/mL indicated non-EH with a sensitivity and specificity of 0.682 and 1.000, respectively. The area under the curve (AUC) of serum activin A for detecting non-EH was 0.791 (95% confidence interval (CI), 0.618 - 0.964), while that of CRP was 0.723 (95% CI, 0.504 - 0.941). Conclusions: The serum activin A level is a potential novel biomarker of endoscopic activity in UC.

Current status and future perspective of linked color imaging for gastric cancer screening: a literature review.

Screening endoscopy has advanced to facilitate improvements in the detection and prognosis of gastric cancer. However, most early gastric cancers (EGCs) have subtle morphological or color features that are difficult to detect by white-light imaging (WLI); thus, even well-trained endoscopists can miss EGC when using this conventional endoscopic approach. This review summarizes the current and future status of linked color imaging (LCI), a new image-enhancing endoscopy (IEE) method, for gastric screening. LCI has been shown to produce bright images even at a distant view and provide excellent visibility of gastric cancer due to high color contrast relative to the surrounding tissue. LCI delineates EGC as orange-red and intestinal metaplasia as purple, regardless of a history of Helicobacter pylori (Hp) eradication, and contributes to the detection of superficial EGC. Moreover, LCI assists in the determination of Hp infection status, which is closely related to the risk of developing gastric cancer. Transnasal endoscopy (ultra-thin) using LCI is also useful for identifying gastric neoplastic lesions. Recently, several prospective studies have demonstrated that LCI has a higher detection ratio for gastric cancer than WLI. We believe that LCI should be used in routine upper gastrointestinal endoscopies.

Rheumatoid Arthritis Symptoms Diagnosed by Rheumatic Immune-related Adverse Events Caused by Nivolumab in a Patient with Esophageal Cancer.

This report described the case of a 70-year-old man who developed polyarthralgia after nivolumab treatment for recurrent esophageal cancer. Arthritis developed after initiating nivolumab therapy, and the patient tested positive for rheumatoid factor and anti-citrullinated peptide antibodies. The hand and elbow joints were already deformed, suggesting that he had had rheumatoid arthritis for several years and that the symptoms had only become apparent after nivolumab administration. This patient had rheumatoid arthritis, which was diagnosed as a nivolumab-induced rheumatic immune-related adverse event (rh-irAEs). Arthralgia during nivolumab administration can occur in rh-irAE cases. Patients should be assessed for autoimmune diseases before initiating immune checkpoint inhibitors.

Comparative study between histochemical mucus volume, histopathological findings, and endocytoscopic scores in patients with ulcerative colitis.

Ulcerative colitis (UC) causes a reduction in goblet cells. However, there have been few reports on the relationship between endoscopic and pathological findings and mucus volume. In this study, we quantitatively evaluated histochemical colonic mucus volume by fixing biopsied tissue sections taken from patients with UC in Carnoy's solution and compared it with endoscopic and pathological findings to determine whether there is a correlation between them. Observational study. A single-center, university hospital in Japan. Twenty-seven patients with UC (male/female, 16/11; mean age, 48.4 years; disease median duration, 9 years) were included in the study. The colonic mucosa of the most inflamed area and the surrounding less inflamed area were evaluated separately by local MES and endocytoscopic (EC) classification. Two biopsies were taken from each area; one was fixed with formalin for histopathological evaluation, and the other was fixed with Carnoy's solution for the quantitative evaluation of mucus via histochemical Periodic Acid Schiff and Alcian Blue staining. The relative mucus volume was significantly reduced in the local MES 1-3 groups, with worsening findings in EC-A/B/C and in groups with severe mucosal inflammation, crypt abscess, and severe reduction in goblet cells. The severity of inflammatory findings in UC by EC classification correlated with the relative mucus volume suggesting functional mucosal healing. We found a correlation between the colonic mucus volume and endoscopic and histopathological findings in patients with UC, and a stepwise correlation with disease severity, particularly in EC classification.

ATG16L1 and ATG12 Gene Polymorphisms Are Involved in the Progression of Atrophic Gastritis.

Helicobacter pylori (H. pylori) infection causes a progression to atrophic gastritis and results in gastric cancer. Cytotoxin-associated gene A (CagA), a major virulence factor of H. pylori, is injected into gastric epithelial cells using the type IV secretion system. On the other hand, gastric epithelial cells degrade CagA using an autophagy system, which is strictly regulated by the autophagy-related (ATG) genes. This study aimed to identify SNPs in ATG5, ATG10, ATG12, and ATG16L1 associated with gastric mucosal atrophy (GMA). Here, two-hundred H. pylori-positive participants without gastric cancer were included. The degree of GMA was evaluated via the pepsinogen method. Twenty-five SNPs located in the four candidate genes were selected as tag SNPs. The frequency of each SNP between the GMA and the non-GMA group was evaluated. The rs6431655, rs6431659, and rs4663136 in ATG16L1 and rs26537 in ATG12 were independently associated with GMA. Of these four SNPs, the G/G genotype of rs6431659 in ATG16L1 has the highest odd ratio (Odds ratio = 3.835, 95% confidence intervals = 1.337-1.005, p = 0.008). Further functional analyses and prospective analyses with a larger sample size are required.

A Novel Monochromatic Light to Detect Target Specimens Within Endoscopic Ultrasonography-guided Fine-needle Aspiration Biopsy Samples.

BACKGROUND/AIM: Endoscopic ultrasonography (EUS)-guided fine-needle aspiration biopsy (EUS-FNB) enhances the diagnostic capabilities of EUS by providing additional pathological samples. However, detecting the target specimens within the collected samples can be challenging. The aim of this study was to determine the optimal wavelength of light for detection of target specimens within EUS-FNB samples in an animal experiment. MATERIALS AND METHODS: EUS-FNB pancreatic tissue samples were collected from a male beagle (weight, 10 kg), and the samples were illuminated with monochromatic light ranging from 430 to 700 nm in 5-nm intervals. The intensities of the target specimen and blood samples were analyzed using the densitometry of the images obtained through irradiation. RESULTS: We found that transmitted monochromatic light of 605 nm most vividly enhanced the contrast between the target specimens and blood in the samples in the impression of appearance. CONCLUSION: Thus, microscopical observations under transmitted light of 605 nm are optimal for target tissue identification within EUS-FNB samples.

Pancreatic Juice Cytology Evaluations Using Synthetic Secretin and Serial Pancreatic Juice Aspiration Cytological Examination for the Diagnosis of Pancreatic Ductal Adenocarcinoma.

Pathological examination by endoscopic ultrasound-fine needle aspiration is not possible in approximately 10% of pancreatic tumor cases. Pancreatic juice cytology (PJC) is considered an alternative diagnostic method. However, its diagnostic capability is insufficient, and PJC has been repeatedly redevised. Serial pancreatic juice aspiration cytological examination (SPACE) and secretin-loaded PJC (S-PJC) have been recently introduced as alternative diagnostic methods. This study aimed to determine the diagnostic capacity and safety of SPACE and S-PJC using a propensity score-matched analysis. The sensitivity, specificity, and accuracy were 75.0%, 100%, and 92.3% for S-PJC, respectively, and 71.4%, 100%, and 92.3% for SPACE, respectively, meaning that there was no significant difference between the groups. Four patients (15.4%) each in the S-PJC and SPACE groups experienced complications, including postendoscopic retrograde cholangiopancreatography, pancreatitis, and cholangitis. Overall, there was no difference in efficacy and safety between the SPACE and S-PJC groups.