Factors Affecting Technical Difficulty in Balloon Enteroscopy-Assisted Endoscopic Retrograde Cholangiopancreatography in Patients with Surgically Altered Anatomy.

Success rates of balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) for patients with a reconstructed intestinal tract after surgical procedures are unsatisfactory. We retrospectively investigated the factors associated with unsuccessful BE-ERCP. Ninety-one patients who had a reconstructed intestinal tract after gastrectomy or choledochojejunostomy were enrolled. Age, sex, operative method, malignancy, endoscope type, endoscopist's skill, emergency procedure, and time required to reach the papilla/anastomosis were examined. The primary endpoints were the factors associated with unsuccessful BE-ERCP selective cannulation, while the secondary endpoints were the rate of reaching the papilla/anastomosis, causes of failure to reach the papilla/anastomosis, cannulation success rate, procedure success rate, and rate of adverse events. Younger age (odds ratio, 0.832; 95% CI, 0.706-0.982; p = 0.001) and Roux-en-Y partial gastrectomy (odds ratio, 54.9; 95% CI, 1.09-2763; p = 0.045) were associated with unsuccessful BE- ERCP. The rate of reaching the papilla/anastomosis was 92.3%, the success rate of biliary duct cannulation was 90.5%, procedure success rate was 78.0%, and the rate of adverse events was 5.6%. In conclusion, Roux-en-Y partial gastrectomy and younger age were associated with unsuccessful BE-ERCP. If BE-ERCP is extremely difficult to perform in such patients after Roux-en-Y partial gastrectomy, alternative procedures should be considered early.

Interobserver Reliability of the Endoscopic Ultrasound Criteria for the Diagnosis of Early Chronic Pancreatitis: Comparison between the 2009 and 2019 Japanese Diagnostic Criteria.

In 2009, diagnostic criteria for early chronic pancreatitis (DCECP2009) were proposed by the Japan Pancreas Society. This study aimed to evaluate the interobserver reliability (IOR) of endoscopic ultrasound (EUS) criteria for diagnosis of early chronic pancreatitis (ECP) between DCECP2009 and 2019 diagnostic criteria for ECP (DCECP2019) to assess the validity of the revision from the perspective of EUS findings. Among patients who underwent a detailed observation of the pancreas by EUS at our institution between January 2018 and March 2019, EUS images of 97 patients were extracted. Images were reviewed by 12 gastrointestinal endoscopy experts (eight pancreatologists, group A and four nonpancreatologists, group B). The overall kappa (K)-values for the IOR of the DCECP2009 EUS criteria were 0.424 and 0.563:0.231 for groups A:B, whereas the overall K-values for the DCECP2019 criteria were 0.618, and 0.733:0.442 for groups A:B. Regarding changes in the final diagnosis of ECP based on clinical features and EUS findings, 20 cases were definite ECP, 53 were probable ECP, and 24 were normal according to DCECP2009. In contrast, seven were definite ECP, 19 were probable ECP, and 71 were normal according to DECEP2019. IOR of DCECP2019 was higher than that of DCECP2009, which indicates an improvement in precision.

Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system.

Vasoactive intestinal peptide (VIP), a gut peptide hormone originally reported as a vasodilator in 1970, has multiple physiological and pathological effects on development, growth, and the control of neuronal, epithelial, and endocrine cell functions that in turn regulate ion secretion, nutrient absorption, gut motility, glycemic control, carcinogenesis, immune responses, and circadian rhythms. Genetic ablation of this peptide and its receptors in mice also provides new insights into the contribution of VIP towards physiological signaling and the pathogenesis of related diseases. Here, we discuss the impact of VIP on gastrointestinal function and diseases based on recent findings, also providing insight into its possible therapeutic application to diabetes, autoimmune diseases and cancer.

Duodenal Chemosensing of Short-Chain Fatty Acids: Implications for GI Diseases.

PURPOSE OF REVIEW: Short-chain fatty acids (SCFAs), the main bacterial fermentation products in the hindgut of hindgut fermenters, are also present in the foregut lumen. We discuss the impact of SCFAs in the duodenal defense mechanisms and in the gastrointestinal (GI) pathogenesis. RECENT FINDINGS: Luminal SCFAs augment the duodenal mucosal defenses via release of serotonin (5-HT) and glucagon-like peptide-2 (GLP-2) from enteroendocrine cells. Released GLP-2 protects the small intestinal mucosa from nonsteroidal anti-inflammatory drug-induced enteropathy. SCFAs are also rapidly absorbed via SCFA transporters and interact with afferent and myenteric nerves. Excessive SCFA signals with 5-HT3 receptor overactivation may be implicated in the pathogenesis of irritable bowel syndrome symptoms. SCFA production exhibits diurnal rhythms with host physiological responses, suggesting that oral SCFA treatment may adjust the GI clocks. SCFAs are not only a source of energy but also signaling molecules for the local regulation of the GI tract and systemic regulation via release of gut hormones. Targeting SCFA signals may be a novel therapeutic for GI diseases and metabolic syndrome.

Duodenal chemosensing.

PURPOSE OF REVIEW: Luminal chemosensing is a term used to describe how small molecules in the gut lumen interact with the host through surface receptors or via transport into the submucosa. In this review, we have summarized recent advances of understanding luminal chemosensing in the gastroduodenal mucosa, with a particular emphasis on how chemosensing affects mucosal protective responses and the metabolic syndrome. RECENT FINDINGS: In the past decade, data have supported the hypothesis that gut luminal chemosensing not only is important for the local or remote regulation of gut function but also contributes to the systemic regulation of metabolism, energy balance and food intake. We have provided examples of how luminal nutrients such as long-chain fatty acids (LCFAs), endogenous compounds such as bile acids, bacterial metabolites such as short-chain fatty acids (SCFAs) and bacterial components such as lipopolysaccharide (LPS) activate cognate receptors expressed on key effector cells such as enteroendocrine cells and inflammatory cells in order to profoundly affect organ function through the initiation or suppression of inflammatory pathways, altering gut barrier function and nutrient uptake, altering gut motility and visceral pain pathways, and preventing mucosal injury. SUMMARY: These recent discoveries in this area have provided new possibilities for identifying novel molecular targets for the treatment of mucosal injury, metabolic disorders and abnormal visceral sensation. Understanding luminal chemosensory mechanisms may help to identify novel molecular targets for the treatment and prevention of mucosal injury, metabolic disorders and abnormal visceral sensation.

Multimodal Treatment of Vasoactive Intestinal Polypeptide-producing Pancreatic Neuroendocrine Tumors with Liver Metastases.

A 53-year-old man presented with diarrhoea and hypokalaemia and was diagnosed with a neuroendocrine tumour of unknown origin with multiple liver metastases. Somatostatin analogues led to a reduction in the size of the tumours and improvement of his symptoms. However, after several years, the tumours grew in size, and the patient's clinical symptoms recurred. The patient underwent transcatheter arterial embolization (TAE) of the hepatic artery to treat the liver metastases. Immediately after embolization, the symptoms disappeared. Although the patient had an unresectable vasoactive intestinal polypeptide-producing neuroendocrine tumour, the endocrine symptoms were able to be controlled with chemotherapy and TAE, resulting in a long-term survival.

A case report of gastric linitis plastica diagnosed by endoscopic ultrasound-guided fine needle aspiration.

RATIONALE: There is currently no consensus on the ideal method for obtaining deep tissue biopsy material of advanced gastric LP. EUS-FNA has potential as a useful diagnostic method. Thus, we report the case of a 46-year-old male with advanced gastric linitis plastica (LP) who was diagnosed using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). PATIENT CONCERNS: The patient underwent esophagogastroduodenoscopy (EGD) because of epigastric pain at a local clinic. The gastric fold swelling was pointed out by the EGD and despite the suspected advanced gastric LP, biopsy indicated Group 1. Repeat biopsy did not suggest malignancy. The patient was referred to our institution. DIAGNOSES: Endoscopic ultrasound indicated gastric wall thickening mainly in the greater curvature of the gastric corpus. Low-level echoes were detected throughout the entire gastric wall, and gastric wall layers had been disappeared. EUS-FNA of the gastric wall indicated signet ring cell carcinoma. INTERVENTIONS: As a result of EUS - FNA, it became a policy to administer chemotherapy. In accordance with the patient's wishes, he was referred to another institution for chemotherapy. OUTCOMES: Normal biopsy did not give a definitive pathological diagnosis, and final diagnosis of LP was obtained with EUS-FNA. LESSONS: We expect that EUS-FNA can be utilized as a relatively non-invasive, highly sensitive, and specific pathological diagnostic procedure for advanced gastric LP. EUS-FNA should be considered as one way to obtain a deep tissue biopsy of advanced gastric LP.

Comparison of the usefulness of endoscopic papillary large-balloon dilation with endoscopic sphincterotomy for large and multiple common bile duct stones.

BACKGROUND: Endoscopic sphincterotomy (EST) is currently recognized as the primary endoscopic treatment for common bile duct stones. However, it is difficult to remove multiple (≥ 3) or large (≥ 15 mm) common bile duct stones with EST alone. Recently, EST plus endoscopic papillary large-balloon dilation (EPLBD) was reported to be an effective treatment for such bile duct stones. We compared the results of EST and EST + EPLBD for multiple (≥ 3) or large (≥ 15 mm) stones that were difficult to treat using EST alone. We also compared the complication rates between the techniques. METHODS: Seventy patients with large (largest diameter, ≥ 15 mm) or ≥ 3 common bile duct stones treated in our department between April 2010 and March 2013 underwent EST + EPLBD (n = 34) or EST alone (n = 36). We compared final successful stone removal rates, rates of successful stone removal in the first session, procedure times, status of concurrent mechanical lithotripsy (ML), and complications between the EST + EPLBD and EST groups. RESULTS: The rates of final successful stone removal were similar between the two groups (EST + EPLBD: 100 % vs. EST: 89 %; p = 0.115). The rate of successful stone removal in the first session was significantly higher in the EST + EPLBD group (EST + EPLBD: 88 % vs. EST: 56 %; p = 0.03). Moreover, the procedure time was significantly shorter (EST + EPLBD: 42 min vs. EST: 67 min; p = 0.011) and the rate of ML use was significantly lower in the EST + EPLBD group (EST + EPLBD: 50 % vs. EST: 94 %; p < 0.001). Complications like pancreatitis and bleeding occurred in three patients in the EST + EPLBD group and in 10 patients in the EST group, but the differences were not statistically significant (EST + EPLBD: 9 % vs. EST: 25 %; p = 0.112). CONCLUSIONS: Our results suggest that EST + EPLBD is an effective therapy for patients with difficult-to-treat multiple or large common bile duct stones, because it requires fewer sessions and shorter operative times than EST alone.

Sound variation and function in captive Commerson's dolphins (Cephalorhynchus commersonii).

Commerson's dolphin (Cephalorhynchus commersonii), one of the smallest dolphin species, has been reported to produce only narrow-band high-frequency (NBHF) clicks and no whistles. To clarify their sound repertoire and examine the function of each type, we analysed the sounds and behaviour of captive Commerson's dolphins in Toba Aquarium, Japan. All recorded sounds were NBHF clicks with peak frequency >110kHz. The recorded click-trains were categorised into four types based on the changing pattern of their Inter-click intervals (ICI): Decreasing type, with continuously decreasing ICI during the last part of the train; Increasing type, with continuously increasing ICI during the last part; Fluctuating type, with fluctuating ICI; and Burst-pulse type, with very short and constant ICI. The frequency of the Decreasing type increased when approaching an object newly introduced to the tank, suggesting that the sound is used for echolocation on approach. The Burst-pulse type suddenly increased in front of the object and was often oriented towards it, suggesting that it was used for echolocation in close proximity to the object. In contrast, the Increasing type was rarely recorded during approach, but increased when a dolphin approached another dolphin. The Increasing and Burst-pulse types also increased when dolphins began social behaviours. These results suggest that some NBHF clicks have functions other than echolocation, such as communication.

Synthesis of a natural chromenoquinone via the Diels-Alder reaction of pyranobenzyne and furan.

We describe the total synthesis of angular chromenoquinone 1 isolated from Conospermum plants. Iodophenol, a precursor of pyranobenzyne, was prepared by Claisen rearrangement of an iodoresorcinol derivative. Diels-Alder reaction of the pyranobenzyne and a substituted furan proceeded in low regioselectivity to afford desired 1 and its regioisomer.

Dioxygen activation for the self-degradation of heme: reaction mechanism and regulation of heme oxygenase.

Heme oxygenase (HO) catalyzes the regiospecific conversion of heme to biliverdin, CO, and free iron through three successive oxygenation reactions. HO catalysis is unique in that all three O(2) activations are performed by the substrate itself. This Forum Article overviews our current understanding on the structural and biochemical properties of HO catalysis, especially its first and third oxygenation steps. The HO first step, regiospecific hydroxylation of the porphyrin alpha-meso-carbon atom, is of particular interest because of its sharp contrast to O(2) activation by cytochrome P450. HO was proposed to utilize the FeOOH species but not conventional ferryl hemes as a reactive intermediate for self-hydroxylation. We have succeeded in preparing and characterizing the FeOOH species of HO at low temperature, and our analyses of its reaction, together with mutational and crystallographic studies, reveal that protonation of FeOOH by a distal water molecule is critical in promoting the unique self-hydroxylation. The second oxygenation is a rapid, spontaneous autooxidation of the reactive alpha-meso-hydroxyheme in which the HO enzyme does not play a critical role. Further O(2) activation by verdoheme cleaves its porphyrin macrocycle to form biliverdin and free ferrous iron. This third step has been considered to be a major rate-determining step of HO catalysis to regulate the enzyme activity. Our reaction analysis strongly supports the FeOOH verdoheme as the key intermediate of the ring-opening reaction. This mechanism is very similar to that of the first meso-hydroxylation, and the distal water is suggested to enhance the third step as expected from the similarity. The HO mechanistic studies highlight the catalytic importance of the distal hydrogen-bonding network, and this manuscript also involves our attempts to develop HO inhibitors targeting the unique distal structure.