Outcomes of embolization procedures for type II endoleaks following endovascular abdominal aortic repair.

OBJECTIVE: The objective of this study was to investigate the mid-term outcomes of embolization procedures for type II endoleak after endovascular abdominal aortic repair, and clarify the risk factors for aneurysm enlargement after embolization procedures. METHODS: This was a retrospective multicenter registry study enrolling patients who underwent embolization procedures for type II endoleaks after EVAR from January 2012 to December 2018 at 19 Japanese centers. The primary end point was the rate of freedom from aneurysm enlargement, more than 5 mm in the aortic maximum diameter, after an embolization procedure. Demographic, procedural, follow-up, and laboratory data were collected. Continuous variables were summarized descriptively, and Kaplan-Meier analyses and a Cox regression model were used for statistical analyses. RESULTS: A total of 315 patients (248 men and 67 women) were enrolled. The average duration from the initial embolization procedure to the last follow-up was 31.6 ± 24.6 months. The rates of freedom from aneurysm enlargement at 3 and 5 years were 55.4 ± 3.8% and 37.0 ± 5.2%, respectively. A multivariate analysis revealed that a larger aortic diameter at the initial embolization procedure and the presence of a Moyamoya endoleak, defined as heterogeneous contrast opacity with an indistinct faint border, were associated with aneurysm enlargement after embolization management. CONCLUSIONS: The embolization procedures were generally ineffective in preventing further expansion of abdominal aortic aneurysms in patients with type II endoleaks after EVAR, especially in patients with a large abdominal aortic aneurysm and/or a presence of a Moyamoya endoleak.

Circulating Cell-Free DNA as a Biomarker for Prognosis and Response to Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Systemic therapy provides clinical benefits to a subset of patients with advanced unresectable hepatocellular carcinoma (HCC). However, few biomarkers are available for predicting prognosis and treatment response in patients with advanced HCC undergoing treatment with systemic therapies. This study aimed to examine whether circulating cell-free DNA (cfDNA) containing circulating tumor DNA can act as a therapeutic response and prognostic biomarker in patients with advanced HCC. METHODS: We analyzed longitudinally collected plasma cfDNA of patients with advanced HCC who were naïve to systemic therapy, and assessed their prognostic and predictive values to determine treatment responses. RESULTS: cfDNA concentration positively correlated with entire tumor volume on computed tomography before (p = 0.0231) and at the end (p < 0.0001) of the first-line systemic therapy. The overall survival rate was higher in patients with cfDNA concentrations lower than the median cfDNA level at baseline compared to patients with higher cfDNA concentrations (hazard ratio, 0.2765; 95% confidence interval, 0.08-0.81; p = 0.0197). The ratio of cfDNA at 4 weeks to that at baseline was predictive of radiographic disease response. In patients with progressive disease, cfDNA concentration at 4 weeks increased significantly (p = 0.0245), whereas the concentration remained unchanged in patients with other disease courses (p = 0.9375). CONCLUSION: The baseline plasma cfDNA concentration can be used as a prognostic biomarker in patients with advanced HCC. cfDNA kinetics may also predict the tumor response to therapy and disease progression.

Evaluation of peripheral enhancement on contrast-enhanced computed tomography and corresponding pathological findings in colorectal liver metastases after preoperative chemotherapy.

Purpose: To correlate peripheral enhancement on contrast-enhanced computed tomography (CE-CT) in patients with post-chemotherapy colorectal liver metastases (CRLM) with the corresponding pathological findings. Material and methods: Forty-four patients with CRLM who underwent hepatic resection after preoperative chemotherapy between 2008 and 2013 were included. Two radiologists blinded to the histopathology findings performed a consensus categorization of the marginal contrast effects of CRLM on CE-CT as follows: Group 1, smooth margin without enhancement; Group 2, smooth margin with an enhanced rim; and Group 3, fuzzy margin with/without an enhanced rim. The Kruskal-Wallis test was used to compare the imaging findings with the histological findings. Results: The percentage of infarct-like necrosis was significantly higher in those with CRLM with smooth margins than in those with CRLM with fuzzy margins (p < 0.001, r = 0.62). The percentage of viable cells was lowest in CRLM with smooth margins without enhancement (p < 0.001, r = 0.60). Conclusions: Our findings suggest that the type of necrosis is related to the nature of the margins, and the presence of residual cells is related to peripheral enhancement.

A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation.

BACKGROUND: Ectopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation. CASE PRESENTATION: A 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys). CONCLUSION: We finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.

Lubiprostone Induces Claudin-1 and Protects Intestinal Barrier Function.

INTRODUCTION: Lubiprostone, a chloride channel activator, is said to reduce epithelial permeability. However, whether lubiprostone has a direct effect on the epithelial barrier function and how it modulates the intestinal barrier function remain unknown. Therefore, the effects of lubiprostone on intestinal barrier function were evaluated in vitro. METHODS: Caco-2 cells were used to assess the intestinal barrier function. To examine the expression of claudins, immunoblotting was performed with specific antibodies. The effects of lubiprostone on cytokines (IFNγ, IL-6, and IL-1ß) and aspirin-induced epithelial barrier disruption were assessed by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC) labeled-dextran permeability. RESULTS: IFNγ, IL-6, IL-1ß, and aspirin significantly decreased TEER and increased epithelial permeability. Lubiprostone significantly improved the IFNγ-induced decrease in TEER in a dose-dependent manner. Lubiprostone significantly reduced the IFNγ-induced increase in FITC labeled-dextran permeability. The changes induced by IL-6, IL-1ß, and aspirin were not affected by lubiprostone. The expression of claudin-1, but not claudin-3, claudin-4, occludin, and ZO-1 was significantly increased by lubiprostone. CONCLUSION: Lubiprostone significantly improved the IFNγ-induced decrease in TEER and increase in FITC labeled-dextran permeability. Lubiprostone increased the expression of claudin-1, and this increase may be related to the effect of lubiprostone on the epithelial barrier function.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

The impact of portal vein thrombosis on the prognosis and liver function of nonmalignant cirrhotic patients.

OBJECTIVES: The clinical impact of portal vein thrombosis (PVT) in cirrhotic patients remains unclear. The aim of the study is whether recanalization of acute PVT in nonmalignant cirrhotic patients is associated with their prognosis. MATERIALS AND METHODS: We identified subject with PVT in cirrhotic patients from institutional database. Patients with ≥50% reduction in thrombus size were classified into the improved group and those with ≤49% reduction in thrombus size, or thrombus development in other branches were classified into the deteriorated group. We compared the cumulative survival rate, event-free survival rate (EFS), and liver function (albumin-to-bilirubin (ALBI) and model for end-stage liver disease XI (MELD-XI) between the two groups. RESULTS: Twenty-seven patients were enrolled in this retrospective study. Sixteen patients were classified into the improved group, and 11 were classified into the deteriorated group. In the improved group, the ALBI grade and MELD-XI measured before the onset of PVT and at one year after the onset of PVT were not significantly different. In contrast, MELD-XI was significantly aggravated in deteriorated group (MELD-XI [p = .02]). The cumulative survival of the two groups did not differ significantly; however, the EFS of the deteriorated group was significantly lower (p = .049). CONCLUSIONS: Residual thrombosis of PVT in cirrhotic patients increased the incidence of liver-related events and was associated with the deterioration of the liver function.

Sex differences in associations among metabolic syndrome, obesity, related biomarkers, and colorectal adenomatous polyp risk in a Japanese population.

To investigate sex differences in the associations among metabolic syndrome, obesity, adipose tissue-related biomarkers, and colorectal adenomatous polyps, a cross-sectional, multicenter study was conducted on 489 consecutive individuals who underwent their first colonoscopy at 3 hospitals. Plasma concentrations of adiponectin and leptin, as well as homeostatic model assessment of insulin resistance were also evaluated. The presence and number of adenomatous polyps, including advanced adenoma, were higher in men than in women. Metabolic syndrome was a risk factor for adenomatous polyps in both sexes. Large waist circumference was an independent risk factor for adenomatous polyps in men, and high BMI and large waist circumference were risk factors for adenomatous polyps in women. Interestingly, low BMI was associated with large adenomatous polyps (≥10 mm) and advanced adenoma, and waist-hip ratio was involved in proximal adenomatous polyp development only in women. In contrast, the highest quartile of leptin concentration had a 3.67-fold increased adenomatous polyp risk compared with the lowest quartile only in men. These results indicate that regarding colorectal pathogenesis, sex differences were identified in obesity but not in metabolic syndrome. Visceral obesity and a high serum leptin level may be risk factors for colorectal adenomatous polyp development in Japanese men.

[Diagnosis of duplication of the sigmoid colon prior to surgery:a case study].

A 16-year-old woman identified with colonic distention using chest X-rays visited our hospital. Although abdominal computed tomography (CT), colonoscopy, and barium enema study indicated suspected duplication of the sigmoid colon, the exact portion of communication between the normal colon and the duplicated colon could not be determined. The patient was released, but followed up due to the lack of symptoms. After 7 months, she was urgently re-hospitalized due to the complaint of abdominal pain. Her abdominal CT revealed the wall thickness and distention of the duplication as well as voluminous stool containing barium. After the improvement of her symptoms and on the basis of the inflammatory findings, laparoscopic surgery was performed on the patient. Finally, the lesion was diagnosed as tubular- and continuous-type colonic duplication. Duplication of the colon is a relatively rare occurrence in adulthood. Herein, we report a case of duplication of the sigmoid colon diagnosed prior to surgery in an adult.