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.

Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Renal tubular acidosis without interstitial nephritis in Sjögren's syndrome: a case report and review of the literature.

BACKGROUND: Renal tubular acidosis is the principal clinical feature associated with tubulointerstitial nephritis in patients with primary Sjögren's syndrome. Renal tubular dysfunction due to interstitial nephritis has been considered the underlying pathophysiology connecting renal tubular acidosis and primary Sjögren's syndrome. However, the detailed mechanisms underlying the pathophysiology of renal tubular acidosis in primary Sjögren's syndrome is not fully understood. CASE PRESENTATION: A 30-year-old woman was admitted with complaints of weakness in the extremities. The patient was hospitalized thirteen years earlier for similar issues and was diagnosed with hypokalemic paralysis due to distal renal tubular acidosis with primary Sjögren's syndrome. This diagnosis was based on a positive Schirmer's test. Besides, anti-Sjögren's syndrome-related antigen A was also detected. Laboratory tests indicated distal RTA; however, a renal biopsy showed no obvious interstitial nephritis. Laboratory tests conducted during the second admission indicated distal renal tubular acidosis. Therefore, a renal biopsy was performed again, which revealed interstitial nephritis. Histological analysis of acid-base transporters revealed the absence of vacuolar type H+-ATPases in the collecting duct. The vacuolar type H+-ATPase was also absent in the past renal biopsy, suggesting that the alteration in acid-base transporters is independent of interstitial nephritis. CONCLUSIONS: This case study demonstrates that vacuolar-type H+-ATPases are associated with distal renal tubular acidosis, and distal renal tubular acidosis precedes interstitial nephritis in patients with primary Sjögren's syndrome.

Seasonal Influence on Development of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Retrospective Cohort Study Conducted at Multiple Institutions in Japan (J-CANVAS).

OBJECTIVE: To clarify seasonal and other environmental effects on the onset of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We enrolled patients with new-onset eosinophilic granulomatosis with polyangiitis (EGPA), microscopic polyangiitis (MPA), and granulomatosis with polyangiitis (GPA) registered in the database of a Japanese multicenter cohort study. We investigated the relationship between environmental factors and clinical characteristics. Seasons were divided into 4 (spring, summer, autumn, and winter), and the seasonal differences in AAV onset were analyzed using Pearson chi-square test, with an expected probability of 25% for each season. RESULTS: A total of 454 patients were enrolled, with a mean age of 70.9 years and a female proportion of 55.5%. Overall, 74, 291, and 89 patients were classified as having EGPA, MPA, and GPA, respectively. Positivity for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA was observed in 355 and 46 patients, respectively. Overall, the seasonality of AAV onset significantly deviated from the expected 25% for each season (P = 0.001), and its onset was less frequently observed in autumn. In ANCA serotypes, seasonality was significant in patients with MPO-ANCA (P < 0.001), but not in those with PR3-ANCA (P = 0.97). Additionally, rural residency of patients with AAV was associated with PR3-ANCA positivity and biopsy-proven pulmonary vasculitis. CONCLUSION: The onset of AAV was influenced by seasonal variations and was less frequently observed in autumn. In contrast, the occurrence of PR3-ANCA was triggered, not by season, but by rural residency.

A Novel Non-invasive Qualitative Assay Using Urinary Fluorescence Imaging to Assess Kidney Disease.

In patients with chronic kidney disease, it is necessary to identify the etiology of glomerular disease. Renal biopsy is the gold standard for assessing the underlying pathology; however, it has the risk of potential complications. We have established a urinary fluorescence imaging technique to assess enzymatic activity using an activatable fluorescent probe targeting two enzymes: gamma-glutamyl transpeptidase and dipeptidyl-peptidase. The urinary fluorescence images can be easily obtained by adding an optical filter to the microscope with short incubation of the fluorescent probes. Urinary fluorescence imaging could help to assess underlying etiologies of kidney diseases and is a potential non-invasive qualitative assessment technique for kidney diseases in patients with diabetes. Key features Non-invasive assessment of kidney disease. Urinary fluorescent imaging with enzyme-activatable fluorescent probes. Enables differentiation of diabetic kidney disease and glomerulonephritis.

Identification and Quantification of Jaundice by Trans-Conjunctiva Optical Imaging Using a Human Brain-like Algorithm: A Cross-Sectional Study.

Jaundice is caused by excess circulating bilirubin, known as hyperbilirubinemia. This symptom is sometimes caused by a critical hepatobiliary disorder, and is generally identified as yellowish sclera when bilirubin levels increase more than 3 mg/dL. It is difficult to identify jaundice accurately, especially via telemedicine. This study aimed to identify and quantify jaundice by trans-conjunctiva optical imaging. Patients with jaundice (total bilirubin ≥3 mg/dL) and normal control subjects (total bilirubin <3 mg/dL) were prospectively enrolled from June 2021 to July 2022. We took bilateral conjunctiva imaging with a built-in camera on a smartphone (1st generation iPhone SE) under normal white light conditions without any restrictions. We processed the images using an Algorithm Based on Human Brain (ABHB) (Zeta Bridge Corporation, Tokyo, Japan) and converted them into a hue degree of Hue Saturation Lightness (HSL) color space. A total of 26 patients with jaundice (9.57 ± 7.11 mg/dL) and 25 control subjects (0.77 ± 0.35 mg/dL) were enrolled in this study. The causes of jaundice among the 18 male and 8 female subjects (median age 61 yrs.) included hepatobiliary cancer (n = 10), chronic hepatitis or cirrhosis (n = 6), pancreatic cancer (n = 4), acute liver failure (n = 2), cholelithiasis or cholangitis (n = 2), acute pancreatitis (n = 1), and Gilbert's syndrome (n = 1). The maximum hue degree (MHD) optimal cutoff to identify jaundice was 40.8 (sensitivity 81% and specificity 80%), and the AUROC was 0.842. The MHD was moderately correlated to total serum bilirubin (TSB) levels (rS = 0.528, p < 0.001). TSB level (≥5 mg/dL) can be estimated by the formula 21.1603 - 0.7371 × 56.3-MHD2. In conclusion, the ABHB-based MHD of conjunctiva imaging identified jaundice using an ordinary smartphone without any specific attachments and deep learning. This novel technology could be a helpful diagnostic tool in telemedicine or self-medication.

Atypical Anti-Glomerular Basement Membrane Nephritis After the First Dose of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine.

Atypical anti-glomerular basement membrane (GBM) nephritis is a slowly progressive characterized by linear deposition of immunoglobulin (Ig) G in the GBM without circulating anti-GBM antibodies or lung involvement. There is no established therapy for this disease, and efficacy of the immunosuppressive treatment is questionable. A few cases of atypical anti-GBM nephritis have been reported after administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine. Classic anti-GBM disease has also been reported after the administration of the second dose of the SARS-CoV-2 vaccine. Herein, we present the case of a SARS-CoV-2 vaccine-induced atypical anti-GBM nephritis that developed after the first dose and was unresponsive to immunosuppressive therapy. A 57-year-old Japanese woman developed edema 11 days after the first dose of the SARS-CoV-2 mRNA vaccine. She developed nephrotic-range proteinuria and microscopic hematuria. Renal biopsy revealed endocapillary proliferative glomerulonephritis with linear IgG deposition. However, electron-dense deposits were not detected on electron microscopy. The patient tested negative for circulating anti-GBM antibodies and was diagnosed with atypical anti-GBM nephritis. Although steroids and mizoribine were administered, the patient's renal function deteriorated. In conclusion, atypical anti-GBM nephritis may have earlier onset than the classic anti-GBM disease. Given its uncertainty of effectiveness, immunosuppressive agents should be carefully used for SARS-CoV-2 mRNA vaccine-induced atypical anti-GBM nephritis.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

OBJECTIVES: To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. METHODS: We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. RESULTS: Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. CONCLUSION: Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

The Characteristics and Prognosis of Alpha-Fetoprotein and Des-Gamma-Carboxy Prothrombin Double-Negative Hepatocellular Carcinoma at Baseline in Higher BCLC Stages.

Alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) are widely used as tumor markers to diagnose hepatocellular carcinoma (HCC). Some advanced HCCs demonstrate neither AFP nor DCP. This study investigated the characteristics and prognosis of AFP (<20 ng/mL) and DCP (<40 mAU/ml) double-negative HCC (DNHC) in higher-stage HCC. Between April 2012 and March 2022, 419 consecutive patients were enrolled with newly diagnosed HCC and 372 patients were selected that were diagnosed by histopathology and/or imaging. AFP-negative, DCP-negative, and double-negative HCC were identified in 262 patients (70.4%), 143 patients (38.2%), and 120 patients (32.3%), respectively. In higher-BCLC stages (BCLC-B, C, and D), 17 patients (14.7%) were DNHC. Although there was no difference in BCLC staging, there were more cases under TNM Stage III in DNHC (71.0% vs. 41.4%, p = 0.026). The median maximum tumor diameter was smaller in DNHC [3.2 (1.8−5.0) vs. 5.5 (3.5−9.0) cm, p = 0.001] and their median survival time was significantly better, even in higher-stage HCC [47.0 (24.0−84.0) vs. 19.0 (14.0−30.0) months, p = 0.027). DNHC in higher-BCLC stage HCC is independent of BCLC staging, characterized by a tumor diameter < 5 cm, and is treatable with a good prognosis.

A Novel Imaging Technique for The On-site Assessment of Renal Biopsy Specimens.

When performing renal biopsy, it is necessary to identify the cortex, where glomeruli are exclusively distributed, to ensure the quality of the specimen for histological diagnosis. However, conventional methods using a stereomicroscope or magnifying lens often fail to clarify the quality of the specimen. We have established a fluorescent-based imaging technique for the on-site assessment of renal biopsy specimens. The fluorescent images can be easily obtained by adding an optical filter to the microscope and with a short incubation of an activatable fluorescent probe. This novel imaging technique can be applied to renal biopsy specimens for distinguishing the renal cortex.

Hypertrophic pachymeningitis in ANCA-associated vasculitis: a cross-sectional and multi-institutional study in Japan (J-CANVAS).

BACKGROUND: This study investigated the characteristics of hypertrophic pachymeningitis (HP) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), using information from a multicenter study in Japan. METHODS: We analyzed the clinical information of 663 Asian patients with AAV (total AAV), including 558 patients with newly diagnosed AAV and 105 with relapsed AAV. Clinical findings were compared between patients with and without HP. To elucidate the relevant manifestations for HP development, multivariable logistic regression analyses were additionally performed. RESULTS: Of the patients with AAV (mean age, 70.2 ± 13.5 years), HP was noted in 30 (4.52%), including 20 (3.58%) with newly diagnosed AAV and 10 (9.52%) with relapsed AAV. Granulomatosis with polyangiitis (GPA) was classified in 50% of patients with HP. A higher prevalence of GPA was significantly observed in patients with HP than in those without HP in total AAV and newly diagnosed AAV (p < 0.001). In newly diagnosed AAV, serum proteinase 3 (PR3)-ANCA positivity was significantly higher in patients with HP than in those without HP (p = 0.030). Patients with HP significantly had ear, nose, and throat (ENT) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.03-2.14, p = 0.033) and mucous membrane/eye manifestations (OR 5.99, 95% CI 2.59-13.86, p < 0.0001) in total AAV. Moreover, they significantly had conductive hearing loss (OR 11.6, 95% CI 4.51-29.57, p < 0.0001) and sudden visual loss (OR 20.9, 95% CI 5.24-85.03, p < 0.0001). CONCLUSION: GPA was predominantly observed in patients with HP. Furthermore, in newly diagnosed AAV, patients with HP showed significantly higher PR3-ANCA positivity than those without HP. The ear and eye manifestations may be implicated in HP development.

Intracellular glutathione levels affect the outcomes of verteporfin-mediated photodynamic therapy in esophageal cancer cells.

Photodynamic therapy (PDT) induces cancer cell death by generating reactive oxygen species (ROS). In this process, photosensitizers accumulate in cancer cells irradiated by laser light of a specific wavelength, leading to ROS generation. Verteporfin (VP), a second-generation photosensitizer, is used in PDT for age-related macular degeneration. However, the antitumor effects of VP-PDT remain poorly defined. This study investigated the antitumor effects of VP-PDT on esophageal cancer (EC) cell lines in vitro. Two types of EC cell lines, the KYSE30 cell line, derived from highly differentiated esophageal carcinoma, and the KYSE170 cell line, derived from moderately differentiated carcinoma, were used in this study. VP-PDT exerted effective anticancer effects in both cell lines. Our results revealed that the low-density lipoprotein receptor, albumin receptor, and heme carrier protein-1 in VP uptake were not involved in VP uptake. However, cells rich in intracellular glutathione were resistant to VP-PDT. Our study outcomes suggest that lowering intracellular glutathione via a glutathione synthesis inhibitor or sulfasalazine can increase the effectiveness of VP-PDT-mediated anticancer effects.

Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases.

A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes.

Investigating the role of heat shock protein 47 in fibrosis in Crohn's disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share similar genetic risk factors. However, while fibrotic stricture of the intestine is a major characteristic of CD; it is rarely observed in UC. Deposition of collagen in the extracellular matrix contributes to the formation of fibrotic strictures in CD, but the underlying mechanisms are unknown. In the present study, we found that heat shock protein 47 (HSP47), a stress-response protein that acts as a molecular chaperone during the processing and secretion of collagen, expressed in the intestinal tissue from patients with CD. Serum HSP47 levels and anti-HSP47 antibody titers were significantly higher in patients with CD than in those with UC. Furthermore, anti-HSP47 antibody levels correlated significantly with fibrosis in CD. In addition, HSP47 inhibition significantly suppressed collagen production in fibroblasts in vitro. These findings suggest that HSP47 is a biomarker for differentiating fibrotic from non-fibrotic forms of CD. Additionally, we propose that HSP47 could be a potential target for treating fibrosis in patients with CD.

5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction.

Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 µM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 µM) was added with PA. The gene expression levels of the nuclear factor erythroid 2-related factor 2 (NRF2), HO-1, Glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), PKR-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), C/EBP homologous protein (CHOP), and B-cell lymphoma 2 (BCL-2) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased GRP78 expression in Huh-7 cells. 5-ALA significantly induced HO-1 and decreased GRP78 expression. ATF6 was subsequently decreased. However, NRF2 and CHOP expression were not altered. Anti-apoptotic BCL-2 expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating GRP78 via HO-1 induction.

Photosensitizer verteporfin inhibits the growth of YAP- and TAZ-dominant gastric cancer cells by suppressing the anti-apoptotic protein Survivin in a light-independent manner.

Yes-associated protein (YAP) positivity indicates a poor prognosis in gastric cancer. Transcriptional co-activator with a PDZ-binding domain (TAZ), a YAP paralog, is highly expressed in gastric signet ring cell carcinoma. Verteporfin (VP), a clinical photosensitizer, was recently shown to inhibit YAP/TAZ. In the present study, the therapeutic potential of VP treatment was explored using two gastric cancer cell lines: MKN-45 (TAZ-dominant) and MKN-74 (YAP-dominant). Cell proliferation was evaluated by MTS assay. Vascular mimicry was evaluated by the tube formation assay. Gene and protein expression levels of YAP/TAZ downstream effectors [such as Survivin, Cysteine-rich angiogenic inducer 61 (CYR61), and connective tissue growth factor (CTGF)] were measured. YAP or TAZ localization was evaluated by immunofluorescence. Cell death was assessed by immunofluorescent staining of Annexin V. YAP and TAZ expression were knocked down by small interfering RNA. The current results demonstrate that MKN-45, a poorly differentiated TAZ-dominant gastric cancer cell line, was more sensitive to VP than MKN-74, a moderately differentiated YAP-dominant gastric cancer cell line. VP changed the localization of YAP/TAZ, promoted its degradation and significantly decreased the protein level of Survivin in both cell lines. Cell death was induced by VP treatment in a dose-dependent manner. Vascular mimicry was inhibited in both cell lines. Proliferation in both cell lines decreased in response to YAP/TAZ knockdown. The present study indicated that VP has potential as a therapeutic agent in YAP- and TAZ-dominant gastric cancers due to its ability to suppress the anti-apoptotic protein Survivin via inhibition of YAP and TAZ.

New Closure Method Using Loop and Open-Close Clips after Endoscopic Submucosal Dissection of Stomach and Colon Lesions.

Endoscopic submucosal dissection (ESD) and en bloc resection of stomach and colon tumors have become common. However, mucosal defects resulting from ESD may cause delayed bleeding and perforation. To prevent adverse events, we developed a new clip closure technique, namely, the loop and open-close clip closure method (LOCCM), and aimed to examine its efficacy after ESD for stomach and colon tumors. The LOCCM uses loop and open-close clips. Here, the open-close clip was used to grasp the loop to bring it to the edge of the post-ESD mucosal defect. Another clip with a loop was then inserted into the opposite edge and clipped to the contralateral mucosa to pull both edges together. Once apposed, additional clips facilitated complete closure. The LOCCM was performed in 19 patients after ESD at Tottori University between October 2020 and March 2021. The outcomes retrospectively analyzed were the LOCCM success and adverse event rates. The complete closure rate using LOCCM was 89.5% and none of the patients had post-ESD bleeding or perforation. The results show that LOCCM is an effective and safe closure technique for mucosal defects after stomach and colon ESD to prevent bleeding and perforation.

Impact of endoscopic submucosal dissection and epithelial cell sheet engraftment on systemic cytokine dynamics in patients with oesophageal cancer.

The tumour microenvironment (TME) plays an important role in cancer development, progression, and metastasis. Various cytokines are present in the TME in oesophageal cancer. Oesophageal stricture is a major complication of endoscopic submucosal dissection (ESD) for oesophageal cancer, and inflammatory cytokines are closely related to its pathogenesis. However, the cytokine crosstalk involved in the oesophageal cancer TME and post-ESD stricture has not been fully elucidated. This study investigated the comprehensive cytokine dynamics following ESD in patients with oesophageal cancer. In addition, the effect of a novel preventive technique for post-ESD stricture, autologous cell sheet engraftment, on cytokine levels was evaluated. Various pro-inflammatory and anti-tumorigenic cytokines were elevated in patients with oesophageal cancer, and ESD transiently influenced cytokine concentrations. IL-1ß and TNF-α, two major pro-inflammatory cytokines that induce oesophageal stricture, were significantly suppressed by cell sheet engraftment. In conclusion, this study revealed the distinct cytokine dynamics after ESD in patients with oesophageal cancer, together with the effect of autologous cell sheet engraftment on cytokine fluctuation. These results can accelerate research on the TME and therapeutic strategies for oesophageal cancer.

Neutrophil-to-Lymphocyte Ratio Is a Useful Marker for Predicting Histological Types of Early Gastric Cancer.

BACKGROUND: The indications for endoscopic submucosal dissection (ESD) for gastric cancer are based on preoperative histological assessment; however, examination of tissue biopsy is not always reliable as only a limited portion of the lesion can be obtained. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of inflammatory response and are potentially associated with the grade of malignancy in gastric cancer. We aimed to investigate the association between NLR and PLR and the histology of gastric cancer. METHODS: This study included 218 patients who underwent ESD for gastric cancer. The relationship between NLR/PLR and histological diagnosis was investigated. RESULTS: Patients with adenocarcinomas showed significantly higher NLR and PLR than those with adenomas (p < 0.001 and p < 0.05, respectively). Further, patients with undifferentiated adenocarcinoma showed a significantly higher NLR (p < 0.05) than those with differentiated adenocarcinoma. CONCLUSION: This study suggests that NLR could be a useful marker for assessing early gastric cancer.