Unresectable Ulcerative Colitis Associated Colon Cancer in a Young Japanese Patient: A Case Report.

We herein present the case of a 30-year-old Japanese male patient with ulcerative colitis (UC) who was admitted to our hospital because of significant ascites. Upon evaluation, the patient was diagnosed with unresectable UC-associated cancer (UCAC), localized in the transverse colon. Using gene profiling of the tumor tissue, anti-epidermal growth factor receptor (EGFR) antibody combination chemotherapy was selected. Subsequently, the patient exhibited a temporary response to this regimen, with an enhancement in his quality of life and he was able to survive for 12 months. This case underscores the potential benefits of aggressive chemotherapy tailored to the gene profile in UCAC treatment, offering insights into potential avenues for improving the patient prognosis.

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.

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.

Comparison of diagnostic accuracy between linked color imaging and autofluorescence imaging in patients with ulcerative colitis: A prospective observational study.

BACKGROUND AND AIM: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. METHODS: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. RESULTS: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05). CONCLUSIONS: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.

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 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.

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.

Cancer Research in Adenocarcinoma, Adenoma, Adenomatous Polyposis Coli, and Colitis-Associated Neoplasia: A Special Issue.

Recent technological advancements have enabled us to analyze a variety of aspects of colorectal cancer (CRC), including both clinical and basic science [...].

Local recurrence after successful endoscopic submucosal dissection for rectal mucinous mucosal adenocarcinoma: A case report.

BACKGROUND: Mucinous adenocarcinoma of the colorectum is a rare histological subtype characterized by an abundant mucinous component. Mucinous tumors are frequently diagnosed at an advanced stage, which indicates an aggressive subtype. However, few case reports have been published, and little information is available concerning genetic alterations in mucinous adenocarcinoma. CASE SUMMARY: A 76-year-old man underwent en bloc endoscopic submucosal dissection (ESD) for the management of a type 0-Is+IIa lesion. Histological examination revealed an intramucosal mucinous adenocarcinoma with signet-ring cell carcinoma and well-to-moderately differentiated tubular adenocarcinoma. Three years after the ESD, local recurrence was detected by an endoscopic examination, revealing a new 0-Is+IIa lesion with a phenotype similar to the previously resected lesion. Re-ESD was chosen for the management of the recurrent tumor, and the histological examination showed positive tumor infiltration at the vertical margin. Additional surgical resection was performed for the curative treatment. Genetic analysis showed pathogenic alterations in RNF43 and TP53 in the adenoma and an additional SMAD4 alteration in the carcinoma. CONCLUSION: This mucinous mucosal adenocarcinoma case was suggested to have an aggressive phenotype and a careful and close follow-up are required.

Nasal breathing is superior to oral breathing when performing and undergoing transnasal endoscopy: a randomized trial.

BACKGROUND : Transnasal endoscopy presents a technical difficulty when inserting the flexible endoscope. It is unclear whether a particular breathing method is useful for transnasal endoscopy. Therefore, we conducted a prospective randomized controlled trial to compare endoscopic operability and patient tolerance between patients assigned to nasal breathing or oral breathing groups. METHODS : 198 eligible patients were randomly assigned to undergo transnasal endoscopy with nasal breathing or with oral breathing. Endoscopists and patients answered questionnaires on the endoscopic operability and patient tolerance using a 100-mm visual analog scale ranging from 0 (non-existent) to 100 (most difficult/unbearable). The visibility of the upper-middle pharynx was recorded. RESULTS : Patient characteristics did not differ significantly between the groups. Nasal breathing showed a higher rate of good visibility of the upper-middle pharynx than oral breathing (91.9 % vs. 27.6 %; P < 0.001). Nasal breathing showed lower mean [SD] scores than oral breathing in terms of overall technical difficulty (21.0 [11.4] vs. 35.4 [15.0]; P < 0.001). Regarding patient tolerance, nasal breathing showed lower scores than oral breathing for overall discomfort (22.1 [18.8] vs. 30.5 [20.9]; P = 0.004) and other symptoms, including nasal and throat pain, choking, suffocating, gagging, belching, and bloating (all P < 0.05). The pharyngeal bleeding rate was lower in the nasal breathing group than in the oral breathing group (0 % vs. 9.2 %; P = 0.002). CONCLUSIONS : Nasal breathing is superior to oral breathing for those performing and undergoing transnasal endoscopy. Nasal breathing led to good visibility of the upper-middle pharynx, improved endoscopic operability, and better patient tolerance, and was safer owing to decreased pharyngeal bleeding.

Gastro-colic Fistula-associated Hypersplenism Causes Pancytopenia in a Patient with Crohn's Disease.

A 24-year-old woman was admitted to our hospital due to abdominal pain and a high fever. She was diagnosed with ileocolonic Crohn's disease (CD), complicated with a gastro-colic fistula and splenomegaly. After initial treatment with an infliximab-biosimilar, all blood cell line counts markedly decreased. Three-dimensional reconstructed computed tomography revealed splenic vein narrowing. Thus, her pancytopenia was deemed to have likely been caused by hypersplenism. Surgery was performed, and clinical remission was maintained without pancytopenia. This is the first report of a CD patient with pancytopenia caused by hypersplenism that was triggered by gastro-colic fistula-associated splenic vein obstruction.

Cytomegalovirus infection in patients with malignant lymphomas who have not received hematopoietic stem cell transplantation.

BACKGROUND: Life-threatening cytomegalovirus infection (CMVI) has been reported even in patients with malignant lymphoma (ML) who have not received hematopoietic stem cell transplantation (w/o HSCT) but had been treated with chemotherapy or radiotherapy. However, the CMVI incidence and risk factors (RFs) in patients with ML w/o HSCT have not been fully elucidated. This study aimed to evaluate the clinical aspects, including incidence and RFs, of CMVI in patients with ML w/o HSCT. METHODS: We retrospectively reviewed all patients with ML who received chemotherapy or radiotherapy in our department from 2005 to 2013. The overall survival (OS), incidence and RFs of CMVI, and other characteristics of patients with CMVI were analyzed. RESULTS: Overall, 236 patients with ML w/o HSCT were evaluated. Of these, 5.5% (13/236) developed CMVI; 54% (7/13) received steroid pretreatment before primary therapy (PT) for ML; and 62% (8/13) received > 2 therapeutic regimens for ML. The OS curve of patients with CMVI was significantly worse than that of patients without CMVI (p < 0.0001, log-rank test). A univariate analysis identified B symptoms (p = 0.00321), serum albumin < 3.5 g/dL (p = 0.0007837), C-reactive protein level > the upper limit of normal (p = 0.0006962), steroid pretreatment before PT for ML (p = 0.0004262), > 2 therapeutic regimens for ML (p = 0.0000818), T cell lymphoma (p = 0.006406), and non-complete remission (p = 0.02311) as RFs for CMVI. A multivariate analysis identified steroid pretreatment before PT for ML [odds ratio (OR): 4.71 (95% confidence interval [CI]: 1.06-21.0); p = 0.0419] and > 2 therapeutic regimens for ML [OR: 9.25 (95% CI: 2.33-36.8); p = 0.00159] as independent RFs for CMVI in patients with ML w/o HSCT. CONCLUSIONS: Attention should be paid to CMVI development in patients with ML w/o HSCT pretreated with steroids or who had multiple therapeutic regimens.

Severe immune checkpoint inhibitor-associated gastritis: A case series and literature review.

Background and study aims Recent advances in cancer treatment have involved the clinical application of immune checkpoint inhibitors (ICIs) for various type of cancers. The adverse events associated with ICIs are generally referred to as immune-related adverse events (irAEs). Gastrointestinal irAEs are a major disorder, but gastritis is not frequently observed. The aims of this study were to elucidate the clinical, endoscopic, and histological characteristics of irAE gastritis. Patients and methods Information on patients treated with ICIs were collected from a single institute over 3 years. IrAE gastritis was identified based on the clinical course and endoscopic and histopathological findings. Of the 359 patients treated with ICIs, four cases of irAE gastritis were identified in clinical records from the endoscopy unit. The endoscopic and histopathological findings were analyzed, and further immunohistochemical studies with immune subtype markers and programmed cell death ligand-1 (PD-L1) antibody were conducted. Results Among four patients with irAE gastritis, the remarkable endoscopic characteristics were network-pattern erosion, erythematous and edematous mucosa with thick purulent discharge, and fragile mucosa. Corresponding histological features were fibrinopurulent exudate, severe inflammatory cell infiltration, and epithalaxia, respectively. The PD-L1 expression rate was ≥ 1 % in the gastric tissue of all patients with gastritis. These patients were treated with prednisolone (PSL) and their symptoms improved within a few days to 2 weeks. Conclusions IrAE gastritis were characterized by specific endoscopic findings. The appropriate endoscopic diagnosis may lead to effective treatment with PSL.

A case report of drug-induced liver injury due to the infliximab biosimilar CT-P13 on switching from original infliximab in a patient with Crohn's disease.

Inflammatory bowel diseases (IBDs) are chronic immune disorders of unclear etiology. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A large number of clinical trials of infliximab biosimilar (CT-P13) have suggested that the administration of biosimilars provides high efficacy and safety similar to that of the originators, with a lower cost, so switching from the original to a biosimilar is considered an acceptable treatment. While several abnormalities of blood examination have been observed in patients with CT-P13 administration, no cases of drug-induced liver injury (DILI) caused by CT-P13 has been reported. A 23-year-old woman had been diagnosed with Crohn's disease and was treated with original infliximab (O-IFX) for 9 years. She developed severe jaundice 1 month after switching from O-IFX to CT-P13. Serologic tests of autoimmune and hepatitis viruses were negative, and ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography revealed no abnormalities. A liver biopsy showed prominent pericentral canalicular cholestasis, without features of steatosis or sclerosing cholangitis, which was consistent with drug-induced cholestasis. The cholestasis improved 10 weeks after the discontinuation of CT-P13, and no DILI redeveloped even after re-switching from CT-P13 to O-IFX. This is the first report of DILI due to switching from O-IFX to CT-P13. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment. Plain Language Summary: A case report of drug-induced liver injury due to switch from original infliximab to infliximab biosimilar Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the entire gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor (TNF) inhibitors are effective for IBD treatment and are cost-effective because they reduce hospital admissions and are associated with fewer surgery requirements and a better quality of life in IBD patients. A biological medicinal product that contains a version of the active substance of an already authorized biological medicinal product. Biosimilars of TNF inhibitors, such as CT-P13, are thought to possess equal efficacy and safety to the original with a lower cost, so switching from the original to a biosimilar considered an acceptable treatment. While several serious adverse reactions of TNF inhibitors have been reported, drug-induced liver injury (DILI) is uncommon, and liver dysfunction due to the administration of CT-P13 has not been reported in IBD patients. We herein report the first case of DILI due to CT-P13 after switching from original infliximab (O-IFX) in a patient with Crohn's disease. While the efficacy and safety of CT-P13 are considered equal to those of O-IFX, clinicians need to be alert for certain severe DILIs when switching from O-IFX to CT-P13 with careful monitoring and appropriate treatment.

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY.

BACKGROUND: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. METHODS: Colorectal NET patients aged 20-74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. RESULTS: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5-9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. CONCLUSIONS: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. TRIAL REGISTRATION NUMBER: UMIN000025215.

Testis-specific hnRNP is expressed in colorectal cancer cells and accelerates cell growth mediating ZDHHC11 mRNA stabilization.

Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy.

Probiotic-derived heptelidic acid exerts antitumor effects on extraintestinal melanoma through glyceraldehyde-3-phosphate dehydrogenase activity control.

BACKGROUND: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo. RESULTS: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group. CONCLUSION: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators.

Endoscopic recanalization for the complete closure of long-gap esophageal atresia after reconstruction surgery.

BACKGROUND: Reconstruction surgery-associated stricture frequently occurs in patients with long-gap esophageal atresia (LGEA). While several endoscopic dilatation methods have been applied and would be desirable, endoscopic recanalization is very difficult in cases with complete esophageal closure. Surgical treatment has been performed for a severe stricture, which causes extensive damage to the infant. No reports have described successful endoscopic recanalization for complete closure due to scarring after surgery for LGEA. We herein report the case of successful endoscopic recanalization by single endoscopist in an LGEA patient with complete closure after reconstruction surgery. CASE PRESENTATION: A seven-month-old boy with LGEA who received reconstruction surgery and gastrostomy immediately after birth presented to our unit due to vomiting and malnutrition. Contrast radiography and peroral endoscopy detected complete closure of the esophagus at the anastomotic site. After confirming the length of stricture as several millimeters, we punctured the center of the lumen with a 25-G puncture needle under fluoroscopy. An endoscope was then inserted via the gastrostomy and the puncture hole was detected at the center of the lumen. After passing the guidewire, endoscopic balloon dilation was performed three times, and the hole was sufficiently dilatated. Oral ingestion was feasible, and his nutritional condition was improved. CONCLUSIONS: To our knowledge, this is the first report to propose a less invasive endoscopic approach to recanalize a site of complete esophageal closure in a LGEA patient after reconstruction surgery by single endoscopist. Our endoscopic procedure using an ultrathin endoscope and puncture needle may be a therapeutic option for the treatment of patients with complete esophageal closure in a LGEA patient after reconstruction surgery.

Carbazochrome sodium sulfonate is not effective for prevention of post-gastric endoscopic submucosal dissection bleeding: A retrospective study.

BACKGROUND: Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration. METHODS: We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0-2. The risk factors of post-ESD bleeding, including CSS administration, were investigated. RESULTS: The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02-14.30; p < 0.05), heparin replacement (OR 4.60, 95% CI 1.02-20.70; p < 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43-31.00; p < 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach. CONCLUSION: CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.