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Patient: Female, 84 Final Diagnosis: Bouveret syndrome Symptoms: Abdominal and/or epigastric pain vomitting Medication: — Clinical Procedure: Electrohydraulic lithotripsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Bouveret syndrome is a rare complication of cholelithiasis that often leads to symptoms of gastric outlet obstruction. Case Report: An 84-year-old woman developed acute abdominal symptoms due to impaction of a gallstone in the horizontal part of the duodenum. The diagnosis was supported by abdominal computed tomography and double balloon endoscopy. Considering her advanced age and the position of the calcified gallstone, we decided to perform electrohydraulic lithotripsy using double balloon endoscopy for treatment. Finally, the impacted stone was removed with reduced size. She was discharged home 10 days after admission without recurrence. Conclusions: This case illustrates that electrohydraulic lithotripsy using double balloon endoscopy is very effective, especially for treatment of Bouveret syndrome caused by gallstone impaction in the horizontal part of the duodenum.

Patient: Male, 73 Final Diagnosis: Pancreatitis Symptoms: Upper abdominal pain Medication: — Clinical Procedure:— Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Adenomatous polyposis coli is an autosomal dominant hereditary disorder. Duodenal adenocarcinoma and adenoma, which are extracolonic lesions, not only affect the prognosis of patients but also cause acute pancreatitis. Case Report: We present the case of a 73-year-old male. He had undergone proctocolectomy for familial adenomatous polyposis and distal gastrectomy (Billroth II reconstruction with Braun anastomosis) for gastric ulcer; he presented with acute pancreatitis caused by ampullary duodenum adenoma. Double-balloon endoscopy showed 2 adenomatous polyps in the major papilla and descending limb of the duodenum. Based on the findings of endoscopy and biopsy, the duodenal polyps were diagnosed as adenomas and classified as Spigelman stage II. Conclusions: Our case report suggests that duodenal surveillance is necessary for patients with adenomatous polyposis coli. In addition, surveillance using double-balloon endoscopy is useful for patients with an altered gastrointestinal anatomy.

Pancreatic cancer is one of the leading causes of cancer-related death, and there is currently little hope of a cure because there are no effective biomarkers for its early detection. Therefore, the search for novel biomarkers that would allow the early detection of pancreatic cancer is ongoing. In this study, the differences between the metabolomes of pancreatic cancer patients with Stage III, Stage IVa, or Stage IVb disease (n = 20) and healthy volunteers (n = 9) were evaluated by metabolomics, which is the endpoint of the Omics cascade and therefore the last step in the cascade before the phenotype. In our experimental conditions using gas chromatography mass spectrometry (GC/MS), a total of 60 metabolites were detected in serum, and the levels of 18 of the 60 metabolites were significantly changed in pancreatic cancer patients compared with those in healthy volunteers. Then, Principal Component Analysis (PCA), which is a basic form of Multiple Classification Analysis, was performed, and the PCA scores plots based on the 60 metabolites highlighted the metabolomic differences between the pancreatic cancer patients and healthy volunteers. The differences between different stages of pancreatic cancer were also assessed by Partial Least Squares Discriminant Analysis (PLS-DA), which is one of Multiple Classification Analysis, and we found that it was possible to discriminate among the Stage III, Stage IVa, and Stage IVb groups. In addition, values of the 9 metabolites in 1 Stage I pancreatic cancer patient were similar to those obtained from the Stage III, Stage IVa, and Stage IVb pancreatic cancer patients. Our findings will aid the discovery of novel biomarkers that allow the early detection of pancreatic cancer by metabolomic approaches.

Background Transcatheter arterial chemoembolization (TACE) and transcatheter arterial infusion chemotherapy (TAI) are increasingly used to treat inoperable liver malignancies. It has not been determined whether standard oral and intravenous administration of antibiotics have different prophylactic effects against post-TACE/TAI infection. We compared the efficacy of oral levofloxacin (LVFX) and intravenous cephazolin (CEZ) in patients receiving TACE/TAI for hepatocellular carcinoma (HCC) using a prospective design. Patients and Methods One hundred twenty-nine eligible subjects with HCC treated by TACE/TAI were analyzed in this study. Patients were randomly assigned by the envelope method to groups who received either intravenous infusion of CEZ at 2 g/day or oral administration of LVFX at 300 mg/day for 5 days. Laboratory data, changes in antibiotic administration from the standard ones, duration of hospital stay, side effects of antibiotics, and infectious complications were assessed. Results There were no significant differences in the WBC counts and serum CRP levels between the groups; there were also no significant inter-group differences in the numbers of infectious and other adverse events. Conclusion Our study findings suggest that the results of peroral administration of LVFX for the prevention of post-procedure infectious complications in patients receiving TACE/TAI for HCC are not inferior to those of intravenous administration of CEZ.

Cronkhite–Canada syndrome (CCS) is a rare nonhereditary syndrome characterized by gastrointestinal polyposis and ectodermal changes [1]. Although several treatments, such as steroids, are available, the prognosis is poor, with a 5-year mortality rate of 55% [2]. A 57-year-old man, who suffered from alopecia, anorexia, severe diarrhea, dystrophic nail changes, and pigmentation on the hands, presented to our hospital. Colonoscopy revealed numerous polyps throughout the colon (●" Fig.1a). Gastroscopy and small-bowel series also showed severe gastric and small-bowel polyposis, and histology showed juvenile-like polyps with mild inflammation. On the basis of these findings, the patient was diagnosed with CCS. He was treated with medications including corticosteroids, antiplasmin agents, and azathioprine; however, the symptoms persisted. He developed intussusception 7 years after diagnosis (●" Fig.1b) and underwent ileocecal resection. As he continued to suffer from frequent relapses, with diarrhea and malnutrition with severe hypoalbuminemia, a different therapeutic strategy was needed to control the disease progression. Supported by a single report finding of high levels of tumor necrosis factor alpha (TNF-α) in tissue affected by CCS [3], implying that antiTNF-α therapy could be useful for CCS patients, the patient was administered infliximab at 200mg every 2 weeks. His general condition improved, and colonoscopy performed 20 months after induction of anti-TNF therapy showed complete remission with the disappearance of polyposis (●" Fig.1c). He now receives 200mg of infliximab every 8 weeks, and has been symptom free for 3 years since the initial administration. There is one report that described strong TNF-α expression in intestinal mucosa affected by CCS, implicating the potential usefulness of anti-TNF-α antibody for patients with CCS. However, to the best of our knowledge, this treatment has not been tested until now [3]. Although we could not detect TNF-α expression in the polyps of this patient by immunohistochemistry (●" Fig.2), given the patient’s dramatic response to therapy, it can be assumed that TNF plays an important role in disease development, perhaps upstream of polyp formation. This case indicates that further basic and clinical research is warranted, and that anti-TNF therapy could be an important new strategy for treatment of CCS.

Background & aims To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. Methods Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. Results The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (r s = 0.7371, P Conclusions Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.

Background To improve the quality of life of colorectal cancer patients, it is important to establish new screening methods for early diagnosis of colorectal cancer. Methodology/Principal Findings We performed serum metabolome analysis using gas-chromatography/mass-spectrometry (GC/MS). First, the accuracy of our GC/MS-based serum metabolomic analytical method was evaluated by calculating the RSD% values of serum levels of various metabolites. Second, the intra-day (morning, daytime, and night) and inter-day (among 3 days) variances of serum metabolite levels were examined. Then, serum metabolite levels were compared between colorectal cancer patients (N = 60; N = 12 for each stage from 0 to 4) and age- and sex-matched healthy volunteers (N = 60) as a training set. The metabolites whose levels displayed significant changes were subjected to multiple logistic regression analysis using the stepwise variable selection method, and a colorectal cancer prediction model was established. The prediction model was composed of 2-hydroxybutyrate, aspartic acid, kynurenine, and cystamine, and its AUC, sensitivity, specificity, and accuracy were 0.9097, 85.0%, 85.0%, and 85.0%, respectively, according to the training set data. In contrast, the sensitivity, specificity, and accuracy of CEA were 35.0%, 96.7%, and 65.8%, respectively, and those of CA19-9 were 16.7%, 100%, and 58.3%, respectively. The validity of the prediction model was confirmed using colorectal cancer patients (N = 59) and healthy volunteers (N = 63) as a validation set. At the validation set, the sensitivity, specificity, and accuracy of the prediction model were 83.1%, 81.0%, and 82.0%, respectively, and these values were almost the same as those obtained with the training set. In addition, the model displayed high sensitivity for detecting stage 0–2 colorectal cancer (82.8%). Conclusions/Significance Our prediction model established via GC/MS-based serum metabolomic analysis is valuable for early detection of colorectal cancer and has the potential to become a novel screening test for colorectal cancer.

Aims: Several screening methods have been applied for the early diagnosis of colorectal cancer, but most colorectal cancer patients are not diagnosed at a localized stage. In order to find novel biomarkers for the diagnosis of colorectal cancer, profiling of the serum levels of fatty acids, which are the main components of fats and are important factors for human metabolism, was performed using the sera of colorectal cancer patients. Materials & methods: A total of 42 colorectal cancer patients and eight healthy volunteers participated in this study. The serum levels of fatty acids, including free fatty acids and esterified fatty acids, were evaluated by gas chromatography/mass spectrometry. Then, partial least squares discriminant analysis was performed on the basis of the serum fatty acids detected by gas chromatography/mass spectrometry. Results: The serum levels of the nine fatty acids exhibited distinct differences between the colorectal cancer patients and healthy volunteers: the levels of four fatty acids were higher in the colorectal cancer patients than the healthy volunteers, and those of the other five fatty acids were lower. These changes were also observed at a very early clinical stage. Furthermore, the levels of very-long-chain fatty acids had a tendency to be increased in the sera of the colorectal cancer patients. Conclusions: The pathogenesis of colorectal cancer leads to changes in the composition of serum fatty acids including free fatty acids and esterified fatty acids. These results suggest that serum fatty acid profiling may be used as a novel diagnostic tool for early-stage colorectal cancer.

manipulating the activity of BMP signalling in vitro. Methods: We performed an immunohistochemical analysis of the expression of BMP signalling components (BMPReceptors and SMADs) in a tissue microarray of 41 patients with pancreatic ductal adenocarcinoma (PDAC) and correlated this to patients' survival. We also compared the expression levels of these components in 51 primary pancreatic tumours with 17 metastases. shRNA against SMAD4 and a plasmid encoding SMAD4 was used to investigate the effect of SMAD4 loss in vitro. The BMPReceptor expression was manipulated using siRNA against in a panel of pancreatic cancer cell lines and effects were analyzed using proliferation and invasion assays. Results: Loss of SMAD4 in patients with PDAC is associated with significantly worse survival (p= 0.025). Moreover, SMAD4 loss is more frequent in the metastases samples compared to the primary tumours (65% vs. 47%). Loss of SMAD4 induces transformation of cancer cells into more aggressive mesenchymal cell type with properties of the cancer stem cells, which proliferate slower and are more resistant to chemotherapy. Importantly, in a group of patients with intact positive SMAD4 expression loss of BMPR1a correlates significantly with a poor prognosis (p=0.02). Activation of BMP signalling in SMAD4 positive cancer cells leads to reduced proliferation, migration and invasion. The importance of BMP Receptor loss is confirmed by showing an increase in proliferation and invasion of pancreatic cancer cells after siRNA mediated knockdown of the BMPReceptors or opposite effect after restitution of BMPR. Conclusion: Loss of BMPR1a and SMAD4 results in poor survival in patients with pancreatic cancers. Inactivation of the BMP pathway increases aggressive tumourigenic properties of pancreatic cancer cells, while activation of the BMP pathway in pancreatic cancer reduces invasive metastatic phenotype of cells. Our data suggest that the BMP pathway can be an attractive target for future therapeutic interventions.