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Simple Summary: WEE1 negatively regulates the G2/M cell cycle checkpoint, allowing sufficient DNA damage repair before mitosis. Cancer cells often have a defective G1/S checkpoint and rely on the G2/M checkpoint for DNA damage repair. In this study, we investigated the association between WEE1 expression and clinicopathological features of colorectal cancer (CRC) using surgical specimens. Using various CRC cell lines with different mutation statuses, we compared the effects of the WEE1 inhibitor adavosertib on cell proliferation, cell cycle, and apoptosis induction, especially focusing on p53 and KRAS mutations involved in the G1/S checkpoint. We also performed therapeutic experiments with adavosertib in an orthotopic transplanted CRC mouse model using two cell lines with different mutation statuses to evaluate its antitumor effect and impact on the tumor immune microenvironment. Our findings indicate that WEE1 inhibitors can be used for treating CRC, particularly in cases with p53 mutations. Inhibition of WEE1, a key regulator of the G2/M checkpoint of the cell cycle, induces apoptosis by initiating mitosis without repairing DNA damage. However, the effects of WEE1 inhibitors on the tumor immune microenvironment in colorectal cancer (CRC) remain unclear. Here, we investigated the association between WEE1 expression and CRC clinicopathological features using surgically resected CRC specimens and assessed the antitumor effects of a WEE1 inhibitor using CRC cell lines and orthotopic transplantation mouse models. WEE1 expression was not correlated with the clinicopathological features of CRC. The WEE1 inhibitor suppressed cell proliferation in a concentration-dependent manner in all CRC cell lines. It also increased the percentage of cells in the G2/M phase and apoptotic cells, especially in cell lines with p53 mutations, but did not alter these cell percentages in most p53 wild-type cell lines. In the orthotopic mouse model of CRC, tumor volume was significantly reduced in the WEE1 inhibitor-treated group compared to that in the control group. RNA sequencing and immunohistochemistry analyses of mouse tumors revealed that treatment with the WEE1 inhibitor activated tumor immunity and suppressed stromal reactions. These results demonstrate the potential antitumor effects of WEE1 inhibitors in CRC, particularly in patients with p53 mutations. [ABSTRACT FROM AUTHOR]

Introduction: The virtual scale endoscope (VSE) is a newly introduced endoscope that helps endoscopists in measuring colorectal polyp size (CPS) during colonoscopy by displaying a virtual scale. This study aimed to determine the usefulness of the VSE for CPS measurement and the educational benefit of using VSE images to improve CPS estimation accuracy. Methods: This study included 42 colorectal polyps in 26 patients treated at Hiroshima University Hospital. In study 1, CPS measured using a VSE before endoscopic mucosal resection was compared with CPS measured on resected specimens, and the agreement between the two measurement methods was evaluated via Bland-Altman analysis. In study 2, 14 endoscopists (5 beginners, 5 intermediates, and 4 experts) took a pre-test to determine the size of 42 polyps. After the pre-test, a lecture on CPS measurement using VSE images was given. One month later, the endoscopists took a post-test to compare CPS accuracy before and after the lecture. Results: In study 1, Bland-Altman analysis revealed no fixed or proportional errors. The mean bias ±95% limits of agreement (±1.96 standard deviations) of the measurement error was −0.05 ± 0.21 mm, indicating that the agreement between two measurement methods was sufficient. In study 2, the accuracy of CPS measurement was significantly higher among beginners (59.5% vs. 26.7%, p < 0.01) and intermediates (65.2% vs. 44.3%, p < 0.05) in the post-test than in the pre-test. Conclusion: The VSE accurately measures CPS before resection, and its images are useful teaching tools for beginner and intermediate endoscopists. [ABSTRACT FROM AUTHOR]

Background and Aim: Although small‐bowel capsule endoscopy (CE) is widely used for obscure gastrointestinal bleeding (OGIB), long‐term outcomes for OGIB patients after negative CE remain unclear. Herein, we defined negative CE as P0 (no bleeding potential) or P1 (less likely to bleed), based on the P classification using CE. We aimed to clarify long‐term outcomes of patients with OGIB after negative CE. Methods: This single‐center observational study enrolled 461 consecutive patients with OGIB who underwent CE from March 2014 to October 2021 and were followed up for >1 year. We examined rebleeding rates and predictive factors. Results: Two hundred and twenty‐four (49%) patients had P0, and 237 (51%) had P1 findings. Rebleeding occurred in 9% and 16% of patients in the P0 and P1 groups, respectively. Two patients in the P0 group and 15 in the P1 group showed rebleeding from the small bowel. The rate of small‐bowel rebleeding was significantly lower in the P0 group than that in the P1 group (1% vs 6%, P = 0.002), as was the cumulative rebleeding rate (P = 0.004). In the multivariate analysis, history of endoscopic hemostasis (hazard ratio [HR] = 15.958, 95% confidence interval [CI]:4.950–51.447, P < 0.001) and P1 CE findings (HR = 9.989, 95% CI: 2.077–48.030, P = 0.004) were independently predicted small‐bowel rebleeding. Conclusions: OGIB with P0 CE findings rarely showed rebleeding from the small bowel. Rebleeding may occur in patients with OGIB. Patients with history of endoscopic hemostasis for small‐bowel lesions or P1 CE findings should be followed up intensively. [ABSTRACT FROM AUTHOR]

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently associated with various gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea. Moreover, several cases of refractory diarrhea have been reported after COVID-19 recovery. Herein, we present a case of severe refractory diarrhea associated with COVID-19. Case Presentation: A 50-year-old man with no comorbidities was admitted to our hospital with SARS-CoV-2 pneumonia. His respiratory status deteriorated, and ventilatory management, including extracorporeal membrane oxygenation, was needed. The patient's respiratory condition improved, resulting in a transfer to another hospital for rehabilitation. However, the patient developed diarrhea that worsened to 6,000–7,000 mL/day, and he was transferred to our hospital. We diagnosed the patient with enterocolitis caused by cytomegalovirus infection and treated him with ganciclovir on day 5 after transfer to our hospital. The diarrhea did not improve. We suspected enterocolitis associated with COVID-19 and administered a methylprednisolone pulse (intravenous injection, 1,000 mg/day for 3 days) on day 10 after transfer, resulting in a marked improvement in his symptoms. The prednisolone dose was tapered, and no recurrence of diarrhea was observed thereafter. Conclusion: The prevalence of COVID-19-associated enterocolitis is low, and the pathogenesis of the disease remains unclear. Prednisolone administration should be considered in cases of post-COVID-19 symptoms of severe diarrhea due to a possible abnormal immune response related to COVID-19. [ABSTRACT FROM AUTHOR]

Simple Summary: In advanced colorectal cancer (CRC), tumor-infiltrating T cells (TILs) are reportedly associated with lymph node (LN) metastasis and prognosis. However, there are no reports focusing on early-stage CRC or examining changes in TILs according to the degree of CRC invasion. Therefore, we investigated the relationship between LN metastasis and TILs in early-stage CRC using the triple immunofluorescence method for CD4, CD8, and Foxp3. We also examined changes in TILs during invasion from early-stage CRC to advanced CRC. We found that a higher number of Foxp3+ T cells and higher Foxp3/CD4 and Foxp3/CD8 ratios at the invasive front of the tumor were associated with LN metastasis. Furthermore, tumor invasion was positively correlated with the number of TILs in CRC. This study provides new predictors of LN metastasis in T1b CRC and provides insight into the tumor microenvironment in CRC invasion. The role of tumor-infiltrating T cells (TILs) in colorectal cancer (CRC) and their significance in early-stage CRC remain unknown. We investigated the role of TILs in early-stage CRC, particularly in deep submucosal invasive (T1b) CRC. Sixty patients with CRC (20 each with intramucosal [IM group], submucosal invasive [SM group], and advanced cancer [AD group]) were randomly selected. We examined changes in TILs with tumor invasion and the relationship between TILs and LN metastasis risk. Eighty-four patients with T1b CRC who underwent initial surgical resection with LN dissection or additional surgical resection with LN dissection after endoscopic resection were then selected. TIL phenotype and number were evaluated using triple immunofluorescence for CD4, CD8, and Foxp3. All subtypes were more numerous according to the degree of CRC invasion and more abundant at the invasive front of the tumor (IF) than in the center of the tumor (CT) in the SM and AD groups. The increased Foxp3 cells at the IF and high ratios of Foxp3/CD4 and Foxp3/CD8 positively correlated with LN metastasis. In conclusion, tumor invasion positively correlated with the number of TILs in CRC. The number and ratio of Foxp3 cells at the IF may predict LN metastasis in T1b CRC. [ABSTRACT FROM AUTHOR]