ARID1A Is a Prognostic Biomarker and Associated with Immune Infiltrates in Hepatocellular Carcinoma

Objective. ARID1A has been discovered as a potential cancer biomarker. But its role in hepatocellular carcinoma (HCC) is subject to considerable dispute. Methods. The relationship between ARID1A and clinical factors was investigated. Clinicopathological variables related to overall survival in HCC subjects were identified using Cox and Kaplan–Meier studies. The connection between immune infiltrating cells and ARID1A expression was investigated using the tumor Genome Atlas (TCGA) dataset for gene set enrichment analysis (GSEA). Finally, a cell experiment was used to confirm it. Results. The gender and cancer topography (T) categorization of HCC were linked to increased ARID1A expression. Participants with advanced levels of ARID1A expression had a worse prognosis than someone with lower levels. ARID1A was shown to be a risk indicator of overall survival on its own. ARID1A expression is inversely proportional to immune cell infiltration. In vitro, decreasing ARID1A expression substantially slowed the cell cycle and decreased HCC cell proliferation, migration, and invasion. Conclusion. The expression of ARID1A could be used to predict the outcome of HCC. It is closely related to tumor immune cell infiltration.

Preoperative Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and CEA as the Potential Prognostic Biomarkers for Colorectal Cancer

Background. This study was to evaluate the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) in colorectal cancer (CRC) patients and to identify the potential and easily accessible prognostic biomarkers for CRC. Methods. We retrospectively reviewed altogether the records of 330 CRC patients according to inclusion criteria. The clinical characteristics include age at diagnosis, body mass index (BMI), preoperative CEA level, neutrophil , lymphocyte, and platelet count, tumor primary site and size, clinical pathological TNM stage, and survival status were recorded through the review of medical records. The overall survival (OS) was calculated using the Kaplan–Meier method. The Cox proportional hazards model was used for the univariate and multivariate analysis to evaluate the prognostic factors of CRC. Results. A total of 330 patients were finally included in the current study. The mean follow-up duration was 32.8 ± 19.1 months (range, 0.1–67.7). Compared with the median OS, preoperative high NLR, PLR, and CEA, and low BMI had lower median OS. The NLR and PLR value rise indicates lower median OS in stage I-II CRC; however, the NLR value and CEA level rise indicates lower median OS in stage III-IV CRC. Preoperative high NLR, PLR, and CEA level and low BMI have poorer OS by univariate analysis. By multivariate analysis, the age, sex, N, M stage, and BMI demonstrated independently influence the OS of CRC. NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC. Conclusions. Our results show that preoperative high NLR, PLR, CEA, and low BMI had poorer OS, NLR was an independent predictor of stage I-II CRC, and the CEA level was an independent predictor of stage III-IV CRC.

Risk Factors for Esophageal Collateral Veins in Cirrhosis with and without Previous Endoscopic Esophageal Variceal Therapy

Background. Portosystemic collateral vessels are a sign of portal hypertension in liver cirrhosis. Esophageal collateral veins (ECVs) are one major type of portosystemic collateral vessels, which increase the recurrence of esophageal varices and bleeding after variceal eradication. However, the risk factors for ECVs were still unclear. Methods. We retrospectively screened cirrhotic patients who had contrast-enhanced computed tomography (CT) images to evaluate ECVs and upper gastrointestinal endoscopic reports to evaluate gastroesophageal varices at our department. Univariate and multivariate logistic regression analyses were performed to explore the independent risk factors for ECVs. Odds ratios (ORs) were calculated. Subgroup analyses were performed in patients with and without previous endoscopic variceal therapy which primarily included endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). Results. Overall, 243 patients were included, in whom the prevalence of ECVs was 53.9%. The independent risk factors for ECVs were hepatitis C virus infection (OR = 0.250, p = 0.026), previous EVL (OR = 1.929, p = 0.044), platelet (OR = 0.993, p = 0.008), and esophageal varices needing treatment (EVNTs) (OR = 2.422, p = 0.006). The prevalence of ECVs was 60.8% (73/120) in patients undergoing EVL, 50% (10/20) in those undergoing EIS, and 47.5% (48/101) in those without previous endoscopic variceal therapy. The independent risk factors for ECVs were the use of nonselective beta-blockers (OR = 0.294, p = 0.042) and EVNTs (OR = 3.714, p = 0.006) in subgroup analyses of patients with and without previous endoscopic variceal therapy, respectively. Conclusions. The presence of ECVs should be closely associated with the severity of portal hypertension in liver cirrhosis. Risk of ECVs might be increased by previous EVL.

Treatment Effect of a Vascular-Disrupting Agent Dynamically Monitored by DWI: An Animal Experimental Study

Objective. To investigate the treatment effect of a vascular-disrupting agent, M410, using diffusion-weighted imaging in a rabbit model of hepatic VX2 tumor. Methods. 28 New Zealand white rabbit models with VX2 liver tumors were established and were randomly divided into M410 (intravenous injection of M410 at a dose of 25 mg/kg every three days) and control (intravenous injection of saline every three days) groups. Conventional and diffusion-weighted imaging (DWI) were acquired on a 3.0 T MR unit at baseline, 4 h, d 1, d 4, d 7, and d 14 posttreatment. B-value with 700 (s/mm2) was chosen during DWI examinations. Tumor volume and apparent diffusion coefficient (ADC) values of the entire tumor and solid component of the tumor at every time point were measured. Two randomly chosen rabbits from each group were sacrificed for H&E staining and CD34 immunohistochemical assessments at each time point. An independent sample t-test was used to assess differences in tumor sizes and ADC values of the entire tumor and solid component of tumors between two groups, with P < 0.05 considered statistically significant. Result. There was no significant difference in tumor volume between the two groups at baseline, 4 h, and d 1. With time, the tumors in the control group grew significantly faster than those in the M410 group, and the average ADC values of the M410 group were lower than those of the control group at d 1 and higher than those of the control group at d 4; as such, there were statistical differences between the two groups at these two time points but not at the other four time points. The following pathological results reflected the underlying morphological changes and vascular alterations. Conclusions. M410 performed well in inhibiting the growth of the hepatic VX2 tumor which could be noninvasively monitored by DWI metrics.

Prognostic Analysis of Different Metastatic Patterns in Invasive Intraductal Papillary Mucinous Neoplasm: A Surveillance, Epidemiology, and End Results Database Analysis

Objective. To evaluate the impacts of different metastatic patterns on the prognosis of patients with invasive intraductal papillary mucinous neoplasm (IPMN). Materials and Methods. All patients who were diagnosed with invasive IPMN in the Surveillance, Epidemiology, and End Results SEER database (2010–2015) were included in this study. They were grouped according to different metastatic patterns. Kaplan–Meier analysis and log-rank test were used for the comparison of their survival rates. The hazard ratio (HR) with 95% confidence interval (CI) was analyzed using the Cox proportional-hazards model. Results. A total of 2264 cases were included in this study. The most common metastatic site was the liver. The patients with the nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. As compared to the patients with isolated liver metastasis, those with isolated lung and other organ metastases showed better overall survival rates and tumor-specific survival rates. The patients with liver, lung, multiple, and other organ metastases or of age >60 years were the independent predictors of poor prognosis. Conclusions. The patients with isolated lung and other organ metastases demonstrated better survival outcomes as compared to those with isolated liver metastasis. The patients with nonorgan metastasis demonstrated the best survival outcomes, while those with multiple metastases showed the worst survival outcomes. Further studies are needed to determine a highly selected subset of patients, who might benefit from surgery or chemotherapy.

IgG4-Related Sclerosing Cholangitis: Rarely Diagnosed, but not a Rare Disease

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

Age Cutoff and Yield of Prompt Esophagogastroduodenoscopy to Detect Malignancy in Vietnamese with Upper Gastrointestinal Symptoms: An Endoscopic Database Review of 472,744 Patients from 2014 to 2019

Background and Aims. Age cutoff is an important factor in deciding whether esophagogastroduodenoscopy (EGD) is necessary for patients presenting with upper gastrointestinal symptoms. However, the cutoff value is significantly different across populations. We aimed to determine the age cutoff for EGD that assures a low rate of missing upper gastrointestinal malignancy (UGIM) and to assess the yield of prompt EGD in Vietnamese patients presenting with upper gastrointestinal symptoms. Methods. All EGDs performed in outpatients during a 6-year period (2014–2019) at a tertiary hospital that provided an open-access endoscopy service were retrospectively reviewed. Repeat or surveillance EGDs were excluded. Different age cutoffs were evaluated in terms of their prediction of the absence of UGIM. The yield of endoscopy to detect one malignancy (YoE) was also calculated. Results. Of 472,744 outpatients presenting with upper gastrointestinal symptoms, there were 2198 (0.4%) patients with UGIM. The median age and male-to-female ratio of patients with UGIMs were 57.9 ± 12.5 years and 2.5 : 1, respectively. The YoEs in patients <40, 40–60, and >60 years of age were <1, 1–10, and >10 per 1000 EGDs, respectively. The age cutoffs of 30 years in females and 35 years in males could detect 98.2% (95% CI: 97.7%–98.8%) of UGIM cases with a YoE of about 1 per 1000 EGDs. Conclusions. The age cutoff for EGD in Vietnamese should be lower than that recommended by current international guidelines. The strategy of prompt EGD showed a low YoE, and its cost-effectiveness requires further investigation.

Olfm4 Is Highly Expressed in HCC Patients and as a Biomarker and Therapeutic Target for HCC

Hepatocellular carcinoma (HCC) is one of the primary types of cancer that claims many lives worldwide, and its incidence continues to increase. Conventional therapies against liver cancer are inadequate, and the pathogenesis of HCC remains unclear. Thus, not only are more effective therapies to treat HCC required but also identification of the key genes involved in its pathogenesis is important for developing such therapies. This study found that olfactomedin 4 (OLFM4) level is higher in HCC patients than in healthy individuals. Furthermore, HCC patients also have higher messenger ribonucleic acid (mRNA) expression level in HCC tissues than in liver paracancerous tissues. OLFM4 has high predictive capacity as a biomarker for HCC and closely correlates to tumor size. It is confirmed that OLFM4 contributes to cancer cell proliferation, and HIF1α is involved in this process. Thus, the OLFM4/HIF-1α axis might be a target signaling pathway for developing novel drugs to treat HCC.

The Regularity of the Site of Impaction in Recurrent Gallstone Ileus: A Systematic Review and Meta-Analysis of Reported Cases

Objective. Due to the rarity of recurrent gallstone ileus (RGSI), its epidemiological and clinical features are elusive. With a focus on mortality and the site of impaction, this study consolidates the key clinical characteristics of index GSI (IGSI) and RGSI. Methods. A meta-analysis of cases reported on RGSI was performed. Risk factors for mortality and site of impaction were examined, and a subgroup analysis was performed for age, sex, and site of impaction (jejunum, ileum, or others). Results. In the final analysis, 50 (56 individual cases) studies were included. The paired data for the site of impaction was available for 45 patients. Women accounted for 87.3% of all RGSI cases included in the pooled analysis. The median age (interquartile range, IQR) of the patients was 70 (63–76) years, and the median time of recurrence (IQR) was 20.5 (8.5–95.5) days. The overall mortality rate was 11.8%, without correlation between the mortality rate and age, the time of recurrence, or the site of impaction. The region in which the stone was found in RGSI and IGSI was similar in most cases p = 0.002 . Logistic regression also revealed a higher probability of stone impaction in the ileum in RGSI if it was the site of impaction in IGSI. In most cases, enterolithotomy was the preferred method. Conclusions. A high index of suspicion for RGSI should be maintained for older women with a history of GSI. The region where the stone was impacted during IGSI should be investigated first in such patients.

Clinical Outcomes of COVID-19 and Impact on Disease Course in Patients with Inflammatory Bowel Disease

Background and Aims. The impact of COVID-19 has been of great concern in patients with inflammatory bowel disease (IBD) worldwide, including an increased risk of severe outcomes and/or possible flare of IBD. This study aims to evaluate prevalence, outcomes, the impact of COVID-19 in patients with IBD, and risk factors associated with severe COVID-19 or flare of IBD activity. Methods. A consecutive cohort of IBD patients who were diagnosed with COVID-19 infection and followed up at the McGill University Health Care Centre was obtained between March 1, 2020, and April 30, 2021. Demographics, comorbidities, IBD (type, treatments, pre- and post-COVID-19 clinical activity, biomarkers, and endoscopic activity), and COVID-19-related outcomes (pneumonia, hospitalization, death, and flare of IBD disease) were analyzed. Results. A cohort of 3,516 IBD patients was included. 82 patients (2.3%) were diagnosed with COVID-19 infection (median age: 39.0 (IQR 27.8–48.0), 77% with Crohn’s disease, 50% were female). The prevalence of COVID-19 infection in IBD patients was significantly lower compared to the general population in Canada and Quebec (3.5% versus 4.3%, p < 0.001 ). Severe COVID-19 occurred in 6 patients (7.3%); 2 patients (2.4%) died. A flare of IBD post-COVID-19 infection was reported in 8 patients (9.8%) within 3 months. Biologic therapy was held during active COVID-19 infection in 37% of patients. Age ≥55 years (odds ratio (OR): 11.1, 95% CI: 1.8–68.0), systemic corticosteroid use (OR: 4.6, 95% CI: 0.7–30.1), active IBD (OR: 3.8, 95% CI: 0.7–20.8), and comorbidity (OR: 4.9, 95% CI: 0.8–28.6) were factors associated with severe COVID-19. After initial infection, 61% of IBD patients received COVID-19 vaccinations. Conclusion. The prevalence of COVID-19 infection among patients with IBD was lower than that in the general population in Canada. Severe COVID-19, mortality, and flare of IBD were relatively rare, while a large proportion of patients received COVID-19 vaccination. Older age, comorbidities, active IBD disease, and systemic corticosteroid, but not immunosuppressive or biological therapy, were associated with severe COVID-19 infection.