Prognostic value of moderate or massive ascites in patients with advanced gastric cancer.

Advanced gastric cancer is a highly aggressive malignancy. The available literature does not provide the prognostic value of ascites based on their degree, because most clinical trials exclude patients who present with massive ascites. Therefore, this study examined whether the presence or degree of ascites has a prognostic value in 124 patients with advanced gastric cancer. The degree of ascites was assessed using computed tomography and classified as none, small, moderate or massive. The overall survival (OS) was compared based on the presence or degree of ascites. Furthermore, a Cox proportional hazards analysis was performed to ascertain the predictors of OS. The cumulative 1-year and 2-year OS rates in patients without ascites were 43.5 and 20.2%, respectively, whereas those in patients with ascites were 29.1 and 13.6%, respectively (P=0.116). The cumulative 1-year and 2-year OS rates in patients without moderate or massive ascites were 39.5 and 20.9%, respectively; however, those in patients with moderate or massive ascites were 28.0 and 4.0%, respectively (P=0.027). Multivariate analysis showed that diffuse-type [hazard ratio (HR), 1.532; 95% confidence interval (CI), 1.002-2.343; P=0.049], moderate or massive ascites (HR, 2.153; 95% CI, 1.301-3.564; P=0.003) and chemotherapy (HR, 0.189; 95% CI, 0.101-0.352; P<0.001) were significant predictive factors of OS. In conclusion, the present study indicated that moderate or massive ascites may influence the OS of patients with advanced gastric cancer.

Short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery for superficial non-ampullary duodenal epithelial tumors.

BACKGROUND AND AIMS: This retrospective study aimed to compare the short- and long-term outcomes of endoscopic submucosal dissection and laparoscopic and endoscopic cooperative surgery in patients with superficial non-ampullary duodenal epithelial tumors. PATIENTS AND METHODS: We investigated consecutive patients with SNADETs > 10 mm in size who underwent ESD (ESD group) or LECS (LECS group) between January 2015 and March 2021. The data was used to analyze the clinical course, management, survival status, and recurrence between the two groups. RESULTS: A total of 113 patients (100 and 13 in the ESD and LECS groups, respectively) were investigated. The rates of en bloc resection and curative resection were 100% vs. 100% and 93.0% vs. 77.0% in the ESD and LECS groups, respectively, with no significant difference. The ESD group had shorter resection and suturing times than the LECS group, but there were no significant difference after propensity score matching. There were also no differences in the rates of postoperative adverse event (7.0% vs. 23.1%; P = 0.161). The 3-year overall survival (OS) rate was high in both the ESD and LECS groups (97.6% vs. 100%; P = 0.334). One patient in the ESD group experienced recurrence due to liver metastasis; however, no deaths related to SNADETs were observed. CONCLUSION: ESD and LECS are both acceptable treatments for SNADETs in terms of a high OS rate and a low long-term recurrence rate, thereby achieving a comparable high rate of curative resection. Further studies are necessary to compare the outcomes of ESD and LECS for SNADETs once both techniques are developed further.

Underwater endoscopic papillectomy for a small neuroendocrine tumor of the ampulla of Vater.

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET.

Conventional versus underwater endoscopic resection for superficial non-ampullary duodenal epithelial tumours.

BACKGROUND AND OBJECTIVE: Several endoscopic resection methods have been developed as less invasive treatments for superficial non-ampullary duodenal epithelial tumours. This study aimed to compare outcomes of conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours, including resection depth and rate of the muscularis mucosa contained under the lesion. METHODS: This single-centre retrospective cohort study conducted from January 2009 to December 2021 enrolled patients who underwent conventional endoscopic mucosal resection and underwater endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours and investigated their clinicopathological outcomes using propensity score matching. RESULTS: Of the 285 superficial non-ampullary duodenal epithelial tumours, 98 conventional endoscopic mucosal resections and 187 underwater endoscopic mucosal resections were included. After propensity score matching, 64 conventional endoscopic mucosal resections and 64 underwater endoscopic mucosal resections were analysed. The R0 resection rate was significantly higher in underwater endoscopic mucosal resection cases than in conventional endoscopic mucosal resection cases (70.3% vs. 50.0%; P = 0.030). In the multivariate analysis, a lesion diameter > 10 mm (odds ratio 7.246; P = 0.001), being in the 1st-50th treatment period (odds ratio 3.405; P = 0.008), and undergoing conventional endoscopic mucosal resection (odds ratio 3.617; P = 0.016) were associated with RX/R1 resection. Furthermore, in underwater endoscopic mucosal resection cases, the R0 rate was significantly higher for lesions diameter ≤10 mm than >10 mm, and was significantly higher in the 51st-treatment period than in the 1st-50th period. Conventional endoscopic mucosal resection and underwater endoscopic mucosal resection cases showed no significant difference in resection depth and muscularis mucosa containing rate. CONCLUSIONS: Underwater endoscopic mucosal resection may be more acceptable than conventional endoscopic mucosal resection for superficial non-ampullary duodenal epithelial tumours ≤ 10 mm. A steep early learning curve may be acquired for underwater endoscopic mucosal resection. Large multicentre prospective studies need to be conducted to confirm the effectiveness of underwater endoscopic mucosal resection.

Genomic profile and clinical features of MSI-H and TMB-high pancreatic cancers: real-world data from C-CAT database.

BACKGROUND: Microsatellite instability high (MSI-H) and tumor mutational burden high (TMB-high) pancreatic cancer are rare, and information is lacking. Based on the C-CAT database, we analyzed the clinical and genomic characteristics of patients with these subtypes. METHODS: We retrospectively reviewed data on 2206 patients with unresectable pancreatic adenocarcinoma enrolled in C-CAT between July 2019 and January 2022. The clinical features, proportion of genomic variants classified as oncogenic/pathogenic in C-CAT, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) of chemotherapy as first-line treatment were evaluated. RESULTS: Numbers of patients with MSI-H and TMB-high were 7 (0.3%) and 39 (1.8%), respectively. All MSI-H patients were TMB-high. MSI-H and TMB-high patients harbored more mismatch repair genes, such as MSH2, homologous recombination-related genes, such as ATR and BRCA2, and other genes including BRAF, KMT2D, and SMARCA4. None of the 6 MSI-H patients who received chemotherapy achieved a clinical response, including 4 patients treated with gemcitabine plus nab-paclitaxel (GnP) therapy, whose DCR was significantly lower than that of microsatellite stable (MSS) patients (0 vs. 67.0%, respectively, p = 0.01). Among the TMB-high and TMB-low groups, no significant differences were shown in ORR, DCR (17.1 vs. 23.1% and 57.1 vs. 63.1%, respectively), or median TTF (25.9 vs. 28.0 weeks, respectively) of overall first-line chemotherapy. CONCLUSIONS: MSI-H and TMB-high pancreatic cancers showed some distinct genomic and clinical features from our real-world data. These results suggest the importance of adapting optimal treatment strategies according to the genomic alterations.

Underwater clip closure method for mucosal defects after duodenal endoscopic submucosal dissection (with video).

Conventional clip closure of mucosal defects after duodenal endoscopic submucosal dissection decreases the incidence of delayed adverse events, but may result in incomplete closure, depending on size or location. This study aimed to assess the effectiveness of the underwater clip closure method for complete duodenal defect closure without the difficulties associated with conventional closure methods. We investigated 19 patients with 20 lesions who underwent endoscopic submucosal dissection of the duodenum and subsequent mucosal defect closure in underwater conditions at our facility between February 2021 and January 2022. The success rate of the underwater clip closure method was defined as the complete endoscopic closure of the mucosal defect; a success rate of 100% was achieved. The median resected specimen size was 34.3 mm, the median procedure time for mucosal defect closure was 14 min, and the median number of clips used per patient was 12. No delayed adverse events were observed. The underwater clip closure method is a feasible option for complete closure of mucosal defects, regardless of the size or location of a duodenal endoscopic submucosal dissection.

Characteristics of Gastric Mucosa-Associated Microbiota in Patients with Early Gastric Cancer After Successful Helicobacter pylori Eradication.

BACKGROUND: Helicobacter pylori (H. pylori) is widely recognized as a definite carcinogen in gastric cancer (GC). Although H. pylori eradication reduces the risk of GC, GC recurrence has been detected even after successful H. pylori eradication. Recently, the analysis of gut microbiota was reported. AIMS: This study aimed to evaluate the correlation between gastric mucosa-associated microbiota (G-MAM) and early gastric cancer (EGC) after successful H. pylori eradication. METHODS: In this pilot study, G-MAM were collected during the esophagogastroduodenoscopy of 17 patients, receiving H. pylori eradication therapy at least 5 years ago. The patients were divided into those with EGC (the EGC group, 8 patients) and those without EGC (the NGC group, 9 patients). Microbial samples in the greater curvature of the pyloric site were obtained using an endoscopic cytology brush, and the G-MAM profiles of each sample were analyzed using 16S rRNA V3-V4 gene sequencing. RESULTS: Between the two groups, there was no significant difference in the median age, sex, median period after successful eradication of H. pylori, the α diversity, and the average abundance at the phylum level. At the genus level, the average abundance of Unclassified Oxalobacteraceae, Capnocytophaga, and Haemophilus was significantly lower in the EGC group than in the NGC group (0.89 vs. 0.14%, P < 0.01, 0.28 vs. 0.00%, P < 0.01 and 5.84 vs. 2.16%, P = 0.034, respectively). CONCLUSIONS: We demonstrated alternations in the profiles of G-MAM between the two groups. Our results suggest that G-MAM may influence carcinogenesis after successful H. pylori eradication.

Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

A case of gangrenous cystitis with bilateral hydronephrosis 10 years after radiotherapy.

An 84-year-old woman who was admitted for protein-losing gastroenteropathy associated with radiation enteritis 10 years after pelvic radiotherapy developed pyelonephritis. She became anuric despite having an indwelling bladder catheter. Imaging studies revealed bladder wall thickening, bilateral hydroureter formation, and hydronephrosis. Autopsy findings led to a diagnosis of gangrenous cystitis (GC). Our case indicates that radiation-induced late effects may be an indirect cause of GC, not a direct cause as previously suggested, and that GC may induce bilateral vesicoureteral junction obstruction.

Genomic landscape and clinical features of rare subtypes of pancreatic cancer: analysis with the national database of Japan.

BACKGROUND: Special subtypes of pancreatic cancer, such as acinar cell carcinoma (ACC), adenosquamous carcinoma (ASC), and anaplastic carcinoma of the pancreas (ACP), are rare, and so data on them are limited. Using the C-CAT database, we analyzed clinical and genomic characteristics of patients with these and evaluated differences on comparison with pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: We retrospectively reviewed data on 2691 patients with unresectable pancreatic cancer: ACC, ASC, ACP, and PDAC, entered into C-CAT from June 2019 to December 2021. The clinical features, MSI/TMB status, genomic alterations, overall response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) on receiving FOLFIRINOX (FFX) or GEM + nab-PTX (GnP) therapy as first-line treatment were evaluated. RESULTS: Numbers of patients with ACC, ASC, ACP, and PDAC were 44 (1.6%), 54 (2.0%), 25 (0.9%), and 2,568 (95.4%), respectively. KRAS and TP53 mutations were prevalent in ASC, ACP, and PDAC (90.7/85.2, 76.0/68.0, and 85.1/69.1%, respectively), while their rates were both significantly lower in ACC (13.6/15.9%, respectively). Conversely, the rate of homologous recombination-related (HRR) genes, including ATM and BRCA1/2, was significantly higher in ACC (11.4/15.9%) than PDAC (2.5/3.7%). In ASC and ACP, no significant differences in ORR, DCR, or TTF between FFX and GnP were noted, while ACC patients showed a trend toward higher ORR with FFX than GnP (61.5 vs. 23.5%, p = 0.06) and significantly more favorable TTF (median 42.3 vs. 21.0 weeks, respectively, p = 0.004). CONCLUSIONS: ACC clearly harbors different genomics compared with PDAC, possibly accounting for differences in treatment efficacy.

Mucosal Addressin Cell Adhesion Molecule 1 Expression Reflects Mucosal Inflammation and Subsequent Relapse in Patients with Ulcerative Colitis.

BACKGROUND AND AIMS: Mucosal addressin cell adhesion molecule 1 [MAdCAM-1] is upregulated in the vascular endothelium of the colonic mucosa in ulcerative colitis [UC]. Although the association between MAdCAM-1 expression and mucosal inflammation has been discussed, the association with the clinical course of UC patients has not been reported. In this study we investigated not only the association between mucosal MAdCAM-1 expression and mucosal inflammation, but also its association with subsequent relapse in UC patients with clinical remission. METHODS: Eighty UC patients in remission who visited Kyoto Prefectural University of Medicine for follow-up for 2 years were included. Biopsy samples were collected during colonoscopy, and transcriptional expression levels of UC-related cytokines and MAdCAM-1 were quantified using real-time polymerase chain reaction. MAdCAM-1 mRNA expression and protein expression by immunohistochemistry were compared in patients who subsequently relapsed and those who remained in remission and were examined in relation to endoscopic findings, histological activity and cytokine expression. RESULTS: MAdCAM-1 expression was correlated with endoscopic severity, and significantly elevated in histologically active mucosa than inactive mucosa. Furthermore, MAdCAM-1 expression levels were closely correlated with those of several cytokines. MAdCAM-1 mRNA and protein expression were significantly higher in the relapse group than in the remission group, indicating that MAdCAM-1 expression in the mucosa is already elevated in UC patients in clinical remission who subsequently relapse. CONCLUSIONS: MAdCAM-1 expression in the colonic mucosa of UC patients is related to mucosal inflammation and subsequent relapse; it may serve as a marker for both relapse and therapeutic effectiveness in UC.

Obscure gastrointestinal bleeding from a large jejunal lipoma treated using an endoscopic unroofing technique with double balloon enteroscopy: a case study.

Small intestinal lipomas are rare, but may cause obscure gastrointestinal bleeding. The endoscopic unroofing technique excises only the upper third of the lipoma and allows both histological confirmation and complete treatment with minimal risk of perforation. We present a rare case of obscure gastrointestinal bleeding caused by a jejunal lipoma. A 75-year-old man on antiplatelet therapy presented to our department with melena and anemia. Computed tomography revealed he had a 45-mm jejunal submucosal tumor with fat attenuation. Endoscopic resection using an endoscopic unroofing technique with double balloon enteroscopy was successfully performed. The tumor was confirmed to be a lipoma.

Retrospective investigation of mesalamine intolerance in patients with ulcerative colitis.

Mesalamine is a key drug in the treatment of ulcerative colitis (UC) for both induction and maintenance therapy. On the other hand, it is known that there are some cases of mesalamine intolerance that are difficult to distinguish from symptoms due to aggravation of UC. The aim of this study is to investigate the clinical characteristic of mesalamine intolerance in UC. A retrospective, observational study was conducted. We enrolled 31 patients who were diagnosed as mesalamine intolerance between April 2015 to March 2020. We examined clinical features, time to onset, drug types of mesalamine, DLST positive rate, colonoscopy findings, disease activity, and clinical course after diagnosis. The average dose of mesalamine was 3.69 g and DLST-positive was 57.1%. Within the first 2 weeks from the start of mesalamine, 51.6% showed symptoms of intolerance. The serum CRP level was relatively high at ≥10.0 mg/dl in 53.6% of the cases. There was no difference in clinical background, symptoms, or laboratory findings between patients with DLST-positive and negative. In this study, we clarified the clinical characteristics of mesalamine intolerant patients, and found no difference in the clinical background or success rate of desensitization therapy between positive and negative DLST cases.

Association Between the Cool Temperature-dependent Suppression of Colonic Peristalsis and Transient Receptor Potential Melastatin 8 Activation in Both a Randomized Clinical Trial and an Animal Model.

Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperature-treated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion: For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Effect of concomitant use of G-CSF and myelosuppressive chemotherapy on bone marrow and peripheral granulocytes in a mouse model.

Granulocyte-colony stimulating factor (G-CSF) stimulates bone marrow progenitor cell proliferation and enhances neutrophil production. Exogenous G-CSF administration is indicated for chemotherapy-induced neutropenia management. However, there is a paucity of basic research examining the effects of the concomitant use of G-CSF and chemotherapy on myeloid cells in vivo. Whether concomitant G-CSF and chemotherapy adversely affect myeloid cell proliferation have not been determined. Herein, we examined the effects of the concomitant use of pegfilgrastim and 5-fluorouracil on myeloid cells and peripheral blood cells in mouse models. Balb/c mice were treated intraperitoneally with 5-fluorouracil (20 µg/g b.w.) or a vehicle as a control for 5 days, and pegfilgrastim was administered subcutaneously at 1 µg/g b.w. on day 3. As a result, we demonstrated that the concomitant use of pegfilgrastim suppressed the 5-fluorouracil-induced decrease of granulocytic cells in both bone marrow and peripheral blood in mice. To assess the clinical efficacy of early administration of pegfilgrastim during docetaxel, cisplatin, and 5-fluorouracil therapy in patients with esophageal cancer, we retrospectively identified 42 consecutive patients treated with this regimen. The incidence of both febrile neutropenia and grade 4 neutropenia was significantly lower in patients who received pegfilgrastim than in those who did not receive it (P = 0.002 and P = 0.002, respectively). These results suggest that the concomitant use of pegfilgrastim and chemotherapy, consisting of continuous infusions of 5-fluorouracil, improved chemotherapy-induced neutropenia without detrimental effects on proliferating myeloid granulocytic cells.

Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Vacuolar ATPase (V-ATPase) is involved in cancer development. The use of proton pump inhibitors (PPIs) as V-ATPase inhibitors has been reported to enhance the effectiveness of chemotherapy in certain cancers. This study aimed to evaluate the effect of PPIs on chemotherapy for esophageal cancer. METHODS: To investigate the effects of PPIs on esophageal cancer cells, human KYSE50 and 70 cells were plated and 3 PPIs (lansoprazole, esomeprazole, vonoprazan) were added at various concentrations with 5-Fluorouracil (5-FU) to the corresponding cells for a cell viability assay. To investigate the effects of PPI treatment on patients undergoing 5-FU-based therapy in the clinical setting, we retrospectively analyzed the clinical outcomes and chemotherapy-related adverse events in 40 esophageal cancer patients who received 5-FU chemotherapy in our hospital between May 2013 and April 2017. RESULTS: In the viability assays, all PPIs significantly enhanced the cytotoxic effect of 5-FU on the two esophageal cancer cell lines. In the clinical study, PPI-treated patients showed better overall survival (OS) than patients managed without PPI treatment. A multivariate analysis revealed that PPI treatment was independently associated with OS (p = 0.009, HR, 0.33; 95% CI, 0.12-0.76). CONCLUSIONS: PPI treatment may safely enhance chemosensitivity in esophageal cancer patients.

Investigation on the Inhibitory Effect of Wnt-5a on Colonic Mucosal Inflammation in Patients with Ulcerative Colitis.

BACKGROUND: Recent progress in ulcerative colitis (UC) treatment has been remarkable, and various medications have been applied. However, some patients with UC are refractory to treatment and convert to surgery. AIM: To investigate the role of colonic mucosal Wnt-5a expression in the pathogenesis of UC and the effect of bioactive Wnt-5a peptide on colitis in mice. METHODS: Wnt-5a peptide was intraperitoneally administered to mice every day from the beginning of dextran sulfate sodium (DSS) treatment. The severity of colitis was evaluated based on body weight change, colonic length, and histological scores. Colonic mucosal TNF-α and KC mRNA expression levels were measured. This study included 70 patients with UC in clinical remission. Wnt-5a, TNFα, and IL-8 mRNA expression in the rectal mucosa were measured by quantitative real-time polymerase chain reaction using biopsy materials. Wnt-5a mRNA expression levels were compared between patients who relapsed and those in remission. We examined the correlation of Wnt-5a expression with TNF-α and IL-8 expression. RESULTS: Wnt-5a peptide significantly attenuated the severity of DSS-induced colitis. Moreover, mucosal TNF-α and KC mRNA expression were significantly suppressed by Wnt-5a peptide treatment. Wnt-5a mRNA levels were significantly lower in patients with subsequent relapse than in those who remained in remission. Mucosal Wnt-5a was inversely correlated with TNF α and IL-8 expression. CONCLUSION: Wnt-5a peptide suppressed colitis in mice, and decreased Wnt-5a expression was strongly associated with relapse in patients with UC. Wnt-5a may have an inhibitory effect on mucosal inflammation in UC, and Wnt-5a peptide could be a new therapeutic strategy.

Loss of KAP3 decreases intercellular adhesion and impairs intracellular transport of laminin in signet ring cell carcinoma of the stomach.

Signet-ring cell carcinoma (SRCC) is a unique subtype of gastric cancer that is impaired for cell-cell adhesion. The pathogenesis of SRCC remains unclear. Here, we show that expression of kinesin-associated protein 3 (KAP3), a cargo adaptor subunit of the kinesin superfamily protein 3 (KIF3), a motor protein, is specifically decreased in SRCC of the stomach. CRISPR/Cas9-mediated gene knockout experiments indicated that loss of KAP3 impairs the formation of circumferential actomyosin cables by inactivating RhoA, leading to the weakening of cell-cell adhesion. Furthermore, in KAP3 knockout cells, post-Golgi transport of laminin, a key component of the basement membrane, was inhibited, resulting in impaired basement membrane formation. Together, these findings uncover a potential role for KAP3 in the pathogenesis of SRCC of the stomach.

Mucosal interleukin-8 expression as a predictor of subsequent relapse in ulcerative colitis patients with Mayo endoscopic subscore 0.

BACKGROUND AND AIM: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. METHODS: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor-α, interferon γ, interleukin-1ß, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-7, interleukin-8, interleukin-9, interleukin-10, interleukin-12, interleukin-13, interleukin-15, interleukin-17A, interleukin-17F, interleukin-18, interleukin-21, interleukin-22, interleukin-23, interleukin-27, and interleukin-33 was measured by quantitative real-time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. RESULTS: Ten cytokines, including interleukin-2, interleukin-4, interleukin-8, interleukin-10, interleukin-12, interleukin-15, interleukin-17A, interleukin-21, interleukin-23, and interleukin-33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin-8 expression was the most useful predictor. CONCLUSIONS: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin-8 expression was the most useful for predicting relapse.