Risk Factors for Post-Colorectal Endoscopic Submucosal Dissection Bleeding and Efficacy of Carbazochrome Sodium Sulfonate: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. METHODS: First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. RESULTS: The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CONCLUSION: CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.

Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. METHODS: This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. RESULT: A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). CONCLUSION: GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.

[The task of the medical cooperation system for patients with inflammatory bowel disease in the northern and eastern regions of Hokkaido].

In Japan, establishing a medical cooperation system for patients with inflammatory bowel disease (IBD) between IBD flagship and local care hospitals is a crucial task. Thus, this retrospective multicenter cohort study aims to examine the actual state of medical treatment in patients with IBD via a questionnaire survey administered to eight dependent institutes in Hokkaido, Japan. The present results clarified the clinical disparities of IBD treatment and hospital function between IBD flagship hospitals and local care hospitals. Moreover, the understanding level of IBD treatment in medical staff was significantly lower in local care than in IBD flagship hospitals. Furthermore, an abounding experience of IBD treatment affected the understanding level of IBD treatment of both medical doctors and staff. These findings indicate that selecting patients with IBD corresponding to disease activity, educational system for the current IBD treatment, and promotion of team medicine with multimedical staff can resolve clinical discrepancies between IBD flagship and local care hospitals. The IBD treatment inequities in Japan will be eliminated with the development of an appropriate medical cooperation system between IBD flagship and local care hospitals.

Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10-/- Mice.

BACKGROUND & AIMS: Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10-/-) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals. METHODS: Metagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10-/- mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10-/- mice with antibiotic-induced dysbiosis. RESULTS: Early-, but not late-, life engraftment of a single dominant Bacteroides strain of non-antibiotic-treated IL10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10-/- mice that had antibiotic-induced dysbiosis. CONCLUSIONS: Restitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts.

Heterogenous Nuclear Ribonucleoprotein H1 Promotes Colorectal Cancer Progression through the Stabilization of mRNA of Sphingosine-1-Phosphate Lyase 1.

The oncogenic properties of heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) have been reported, although the tumor-promoting mechanism remains unclear. We herein report the mechanism underlying colorectal cancer cell progression mediated by hnRNP H1. The growth of colorectal cancer cells was suppressed by hnRNP H1 downregulation. A terminal deoxynucleotidyl transferase dUTP nick-end labeling assay revealed the anti-apoptotic effect of hnRNP H1 in colorectal cancer cells. An RNA immunoprecipitation assay revealed that hnRNP H1 bound to sphingosine-1-phosphate lyase 1 (SGPL1). Reverse transcription-polymerase chain reaction revealed the high expression of hnRNP H1 mRNA in colorectal cancer cells and Spearman's rank correlation coefficient showed a strong positive correlation between hnRNP H1 mRNA and SGPL1 mRNA. An siRNA of hnRNP H1 decreased SGPL1 mRNA expression in colorectal cancer cells, but not in non-tumorous cells. These findings suggested that hnRNP H1 increased SGPL1 mRNA expression specifically in cancer cells through direct binding. Targeted knockdown of hnRNP H1 or SGPL1 with siRNAs upregulated p53 phosphorylation and p53-associated molecules, resulting in cell growth inhibition, while hnRNP H1 upregulated the mRNA of SGPL1 and inhibited p53 activation, thereby promoting tumor cell growth. This is a novel mechanism underlying colorectal cancer cell progression mediated by hnRNP H1-SGPL1 mRNA stabilization.

Melatonin-mediated downregulation of thymidylate synthase as a novel mechanism for overcoming 5-fluorouracil associated chemoresistance in colorectal cancer cells.

BACKGROUND: 5-Fluorouracil (5-FU) has been established as the first-line chemotherapy for advanced colorectal cancer (CRC); however, acquired chemoresistance is often the cause of poor therapeutic response. Melatonin is a molecule that is associated with circadian rhythms. Although antitumor effects of melatonin have been shown, the underlying mechanism(s) for its activity and its effect, if any, in chemoresistant CRC has not been studied. We aimed to investigate antitumor effects of melatonin, and more specifically its effect on molecular mechanisms in 5-FU resistant CRC cells. METHODS: The cell growth was assessed in CRC cells, patient-derived organoids and 5-FU resistant CRC cells after treatments with melatonin. In addition, the expression of thymidylate synthase (TYMS) and microRNAs (miRNAs) that are targeting TYMS were examined. RESULTS: We observed that melatonin inhibited the cell growth in 5-FU resistant CRC cells. In addition, we found that melatonin significantly promoted apoptosis. Furthermore, a combination of melatonin and 5-FU markedly enhanced 5-FU-mediated cytotoxicity in 5-FU resistant cells. In addition, melatonin significantly decreased the expression of TYMS. Interestingly, this effect was manifested through the simultaneous increase in the expression of miR-215-5p, for which, TYMS serves as the direct downstream target for this miRNA. CONCLUSIONS: Melatonin facilitates overcoming 5-FU resistance through downregulation of TYMS. Melatonin may serve as a potential therapeutic option on its own, or in conjunction with 5-FU, in the treatment of patients with advanced or chemoresistant CRC.Melatonin inhibits the growth of 5-FU resistant colorectal cancer (CRC) cells through upregulation of miR-215-5p and a concomitant downregulation of TYMS. Melatonin may serve as a potential therapeutic option in the treatment of patients with advanced or chemoresistant CRC.

Autofluorescence Imaging Reflects the Nuclear Enlargement of Tumor Cells as well as the Cell Proliferation Ability and Aberrant Status of the p53, Ki-67, and p16 Genes in Colon Neoplasms.

BACKGROUND: Autofluorescence imaging (AFI) is useful for diagnosing colon neoplasms, but what affects the AFI intensity remains unclear. This study investigated the association between AFI and the histological characteristics, aberrant methylation status, and aberrant expression in colon neoplasms. METHODS: Fifty-three patients with colorectal neoplasms who underwent AFI were enrolled. The AFI intensity (F index) was compared with the pathological findings and gene alterations. The F index was calculated using an image analysis software program. The pathological findings were assessed by the tumor crypt density, cell densities, and N/C ratio. The aberrant methylation of p16, E-cadherin, Apc, Runx3, and hMLH1 genes was determined by a methylation-specific polymerase chain reaction. The aberrant expression of p53 and Ki-67 was evaluated by immunohistochemical staining. RESULTS: An increased N/C ratio, the aberrant expression of p53, Ki-67, and the altered methylation of p16 went together with a lower F index. The other pathological findings and the methylation status showed no association with the F index. CONCLUSIONS: AFI reflects the nuclear enlargement of tumor cells, the cell proliferation ability, and the altered status of cell proliferation-related genes, indicating that AFI is a useful and practical method for predicting the dysplastic grade of tumor cells and cell proliferation.

White coat status is a predictive marker for post-esophageal endoscopic submucosal dissection stricture: a retrospective study.

BACKGROUND: Steroid therapy is primarily used to prevent esophageal stricture after endoscopic submucosal dissection (ESD). However, esophageal stricture can still occur after preventive therapy, and the effect of preventive steroid therapy cannot be predicted before stricture formation. This study aimed to clarify the risk factors for esophageal stricture after preventive steroid therapy. METHODS: This was a retrospective study conducted at three institutions. From January 2011 to February 2018, 28 large-sized SENs in 26 patients who had a mucosal defect that involved more than three-quarters of the esophageal circumference were enrolled. We classified white coats on artificial ulcers after esophageal ESD into three groups (thin, moderately thick, thick) based on endoscopic images obtained on postoperative day 7. RESULTS: The white coat status on the artificial ulcer after ESD was a significant risk factor for post-ESD stricture (p < 0.05). The stricture rates in patients with thin, moderately thick and thick white coats were 10.0, 36.4 and 85.7%, respectively. When thin and moderately thick white coats were combined, the stricture rate was 23.8%. The rate of stricture in lesions with thick white coats was significantly higher than that in patients with thin white coats or thin to moderately thick white coats (p < 0.05). The multivariate analysis revealed that the white coat status was an independent factor related to esophageal stricture (odds ratio 13.70, 95% confidence interval 1.22-154.0; p = 0.034). CONCLUSIONS: The thickness of the white coat is a useful marker for predicting the risk of post-ESD stricture and the effectiveness of preventive steroid therapy.

An elevated expression of serum exosomal microRNA-191, - 21, -451a of pancreatic neoplasm is considered to be efficient diagnostic marker.

BACKGROUND: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. METHODS: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. RESULTS: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). CONCLUSIONS: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).

Second-line therapy for Helicobacter pylori eradication causing antibiotic-associated hemorrhagic colitis.

OBJECTIVE: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication. RESULTS: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia. CONCLUSIONS: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.

Quantification of autofluorescence imaging can accurately and objectively assess the severity of ulcerative colitis.

BACKGROUND AND AIMS: No endoscopic examination has been able to evaluate severity of ulcerative colitis (UC) by quantification. This prospective study investigated the efficacy of quantifying autofluorescence imaging (AFI) to assess the severity of UC, which captures the fluorescence emitted from intestinal tissue and then quantifies the intensity using an image-analytical software program. MATERIALS AND METHODS: Eleven endoscopists separately evaluated 135 images of conventional endoscopy (CE) and AFI from a same lesion. A CE image corresponding to Mayo endoscopic subscore 0 or 1 was defined as being inactive. The fluorescence intensities of AFI were quantified using an image-analytical software program (F index; FI). Active inflammation was defined when Matts' histological grade was 2 or more. A cut-off value of the FI for active inflammation was determined using a receiver operating characteristic (ROC) analysis. The inter-observer consistency was calculated by unweighted kappa statistics. RESULTS: The correlation coefficient for the FI was inversely related to the histological severity (r = -0.558, p < 0.0001). The ROC analysis showed that the optimal cut-off value for the FI for active inflammation was 0.906. The average diagnostic accuracy of the FI was significantly higher than those of the CE (84.7 vs 78.5 %, p < 0.01). The kappa values for the inter-observer consistency of CE and the FI were 0.60 and 0.95 in all participants, 0.53 and 0.97 in the less-experienced endoscopists group and 0.67 and 0.93 in the expert group, respectively. CONCLUSIONS: The quantified AFI is considered to be an accurate and objective indicator that can be used to assess the activity of ulcerative colitis, particularly for less-experienced endoscopists.

Decreased numbers of vascular networks and irregular vessels on narrow-band imaging are useful findings for distinguishing intestinal lymphoma from lymphoid hyperplasia.

BACKGROUND: No method for sufficiently making the differential diagnosis of intestinal lymphoma resembling lymphoid hyperplasia (LH) on endoscopy has yet been established. OBJECTIVE: The aim of this study was to evaluate the usefulness of narrow-band imaging (NBI) in diagnosing intestinal lymphoma. DESIGN: Prospective study. SETTING: Single-center study. PATIENTS: Sixty-one patients with primary or systemic lymphoma were enrolled in this study. INTERVENTIONS: The terminal ileum and entire colon were observed by using conventional endoscopy. NBI was subsequently performed when small polypoid lesions were detected. A decrease in the number of vascular networks (DVNs) and the presence of irregular vessels on the surface of the epithelia were defined as characteristic findings of intestinal lymphoma. The diagnostic accuracy of these 2 findings in distinguishing intestinal lymphoma from LH was examined. MAIN OUTCOME MEASUREMENTS: The ability to use NBI to distinguish intestinal lymphoma from LH. RESULTS: Two hundred ninety-four small polypoid lesions, including 59 lymphomas and 235 LH lesions, were detected. The rates of detecting DVNs and the presence of irregular vessels were significantly higher in the lymphoma samples (81.4% and 62.7%) than in the LH samples (25.5% and 4.7%). Based on these findings, the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values for differentiating intestinal lymphoma from LH were 88.8%, 62.7%, 95.3%, 77.1%, and 91.1%, respectively, which are significantly higher than those of conventional endoscopy. LIMITATIONS: Single-center study. CONCLUSION: DVNs and the presence of irregular vessels on NBI are thus considered to be useful findings for differentiating intestinal lymphoma from benign LH.

Probiotic-derived ferrichrome induces DDIT3-mediated antitumor effects in esophageal cancer cells.

Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic Lactobacillus casei, exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an in vivo OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma.

The white ring sign is useful for differentiating between fundic gland polyps and gastric adenocarcinoma of the fundic gland type.

Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn's disease: A multicenter retrospective pilot study.

INTRODUCTION: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. METHODS: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. RESULTS: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. CONCLUSION: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.

A therapeutic barium enema is a practical option to control bleeding from the appendix.

BACKGROUND: Acute lower gastrointestinal hemorrhage originating from the appendix is rare and often intractable, because it is almost impossible to approach the bleeding point by endoscopy. We herein describe the first case of bleeding from the appendix, which was successively controlled by a therapeutic barium enema administered into the appendix. CASE PRESENTATION: A 71-year-old male visited our hospital because of melena. He has been receiving an anti-coagulation drug, ticlopidine hydrochloride, for 10 years. By an emergency colonoscopy, a hemorrhage was detected in the appendix, and the lesion responsible for the bleeding was regarded to exist in the appendix. Two hundred milliliters of 50 W/V% barium was sprayed into the orifice of the appendix using a spraying tube. The bleeding could thus be immediately stopped, and a radiological examination revealed the accumulation of barium at the cecum and the orifice of the appendix. The barium accumulation disappeared by the next day, and no obvious anal bleeding was observed. Two weeks after stopping the bleeding from the appendix, an appendectomy was performed to prevent any further refractory hemorrhaging. The patient has had no complaints of any abdominal symptoms or anal bleeding for 10 months. CONCLUSIONS: A therapeutic barium enema is a useful procedure to control bleeding from the appendix and to avoid emergency surgery, such as partial cecectomy and hemicolectomy.

The safety of vedolizumab in a patient with Crohn's disease who developed anti-TNF-alpha agent associated latent tuberculosis infection reactivation: A case report.

RATIONALE: Latent tuberculosis (TB) infection screening before inducing anti-tumor necrosis factor (anti-TNF) alpha agents is important to prevent TB reactivation. However, latent TB infection reactivation may still occur, and the ideal therapeutic strategy for patients with inflammatory bowel disease (IBD) who develop active TB infection has not been established. Vedolizumab (VDZ) has a good safety profile, with low incidence rates of serious infections. However, its safety in patients with latent TB infection reactivation associated with anti-TNF-alpha agents remains unknown. PATIENT CONCERNS: A 21-year-old Vietnamese male patient presented to our hospital with hemorrhagic stool. He had no personal or family history of IBD or TB. DIAGNOSES: Colonoscopy revealed multiple longitudinal ulcers and a cobblestone appearance in the terminal ileum, as well as multiple small erosions and aphtha throughout the colon. Computed tomography revealed a right lung nodular lesion. Serological interferon-gamma release assay and several culture tests were all negative. Thus, he was diagnosed with ileocolonic Crohn's disease (CD) without TB. INTERVENTIONS: The intravenous anti-TNF-alpha agent administration with an immunomodulator was initiated. OUTCOMES: Computed tomography revealed nodular lesion expansion at the right lung, and serological interferon-gamma release assay was positive. He was diagnosed with latent TB infection reactivation. Anti-TNF-alpha agent with an immunomodulator was immediately discontinued, and anti-TB therapy was initiated. His endoscopic findings were still active, and VDZ was selected for maintenance therapy because VDZ has a favorable safety profile with low incidence rates of serious infections. Consequently, mucosal healing was achieved without active TB relapse. LESSONS: This case report presented a patient in whom VDZ was continued as maintenance therapy without inducing TB relapse in a patient with CD who developed latent TB infection reactivation associated with anti-TNF-alpha agents and summarized the safety profile of VDZ for patients with IBD with active or latent TB infection. VDZ may be a safe option for induction and maintenance therapy in patients with CD, even in cases with latent TB infection reactivation.

The Identification of RNA-Binding Proteins Functionally Associated with Tumor Progression in Gastrointestinal Cancer.

Previous investigations have indicated that RNA-binding proteins (RBPs) are key molecules for the development of organs, differentiation, cell growth and apoptosis in cancer cells as well as normal cells. A bioinformatics analysis based on the mRNA expression and a somatic mutational database revealed the association between aberrant expression/mutations of RBPs and cancer progression. However, this method failed to detect functional alterations in RBPs without changes in the expression, thus leading to false negatives. To identify major tumor-associated RBPs, we constructed an siRNA library based on the database of RBPs and assessed the influence on the growth of colorectal, pancreatic and esophageal cancer cells. A comprehensive analysis of siRNA functional screening findings using 1198 siRNAs targeting 416 RBPs identified 41 RBPs in which 50% inhibition of cell growth was observed in cancer cells. Among these RBPs, 12 showed no change in the mRNA expression and no growth suppression in non-cancerous cells when downregulated by specific siRNAs. We herein report for the first time cancer-promotive RBPs identified by a novel functional assessment using an siRNA library of RBPs combined with expressional and mutational analyses.

Probiotic­derived ferrichrome inhibits the growth of refractory pancreatic cancer cells.

Pancreatic cancer is associated with a poor prognosis due to challenges in early detection, severe progression of the primary tumor, metastatic lesions, and resistance to antitumor agents. However, previous studies have indicated a relationship between the microbiome and pancreatic cancer outcomes. Our previous study demonstrated that ferrichrome derived from Lactobacillus casei, a probiotic bacteria, exhibited tumor­suppressive effects in colorectal and gastric cancer, and that the suppressive effects were stronger than conventional antitumor agents, such as 5­fluorouracil (5­FU) and cisplatin, suggesting that certain probiotics exert antitumorigenic effects. However, whether or not probiotic­derived molecules, including ferrichrome, exert a tumor­suppressive effect in other gastrointestinal tumors, such as pancreatic cancer, remains unclear. In the present study, it was demonstrated that probiotic­derived ferrichrome inhibited the growth of pancreatic cancer cells, and its tumor­suppressive effects were further revealed in 5­FU­resistant pancreatic cancer cells in vitro and in vivo in a mouse xenograft model. Ferrichrome inhibited the progression of cancer cells via dysregulation of the cell cycle by activating p53. DNA fragmentation and cleavage of poly (ADP­ribose) polymerase were induced by ferrichrome treatment, suggesting that ferrichrome induced apoptosis in pancreatic cancer cells. A transcriptome analysis revealed that the expression p53­associated mRNAs was significantly altered by ferrichrome treatment. Thus, the tumor­suppressive effects of probiotics may mediated by probiotic­derived molecules, such as ferrichrome, which may have applications as an antitumor drug, even in refractory and 5­FU­resistant pancreatic cancer.