A New Bitterness Evaluation Index Obtained Using the Taste Sensor for 48 Active Pharmaceutical Ingredients of Pediatric Medicines.

The aim of this study was to evaluate bitterness by using "CCDP; Change in concentration-dependent potential" considering dose-dependency of active pharmaceutical ingredients (APIs) as new and useful bitterness evaluation index compared with bitter sensor output value which is conventional bitterness evaluation index for 48 pediatric medicines from the recent edition of the WHO model list of essential medicines for children (7th edn, 2019). Solutions (0.01, 0.03, 0.1 mM) of the compounds were evaluated by an artificial taste sensor using membranes sensitive to bitterness. The dose-response slope of the sensor outputs was defined as CCDP. On the basis of principal component analysis of CCDPs, chlorpromazine hydrochloride, amitriptyline hydrochloride, propranolol hydrochloride, primaquine phosphate and haloperidol were predicted to express the strongest levels of basic bitterness, surpassing that of quinine hydrochloride. Correlation analysis (Fisher's exact tests and multiple regression analysis) was performed to determine the relation between CCDPs and various physicochemical properties participated in hydrophilicity and hydrophobicity. It is revealed that contribution physicochemical factors are different by individual basic bitterness sensor (AC0, AN0 or BT0), and this result becomes the criterion of the sensor choice to evaluate basic bitterness intensity using basic bitterness sensors. Hydrophobic and hydrophilic interactions could be simulated by ligand docking modeling for haloperidol, miconazole and quinine hydrochloride. The pharmaceutical products need a bitterness evaluation in consideration of concentration-dependency to vary in a dose depending on a patient individual. Thus, it was concluded that CCDP correlated to hydrophilicity and hydrophobicity is useful as a bitterness evaluation index of APIs in pediatric medicines.

Splenic marginal zone lymphoma uncovered after a 10-year follow up as anemia of unknown cause.

A 75-year-old man was referred to our hospital for evaluation of persistent anemia. Despite repeated diagnostic tests, including bone marrow aspiration, the cause of his anemia remained unknown. On each occasion, computed tomography had revealed neither swollen lymph nodes nor splenomegaly. After a 10-year follow-up period, he was admitted with general fatigue and had developed splenomegaly as well as the anemia. Bone marrow biopsy revealed increased abnormal lymphocytes with short villi that were positive for CD11c, CD19, CD20, and kappa chain, but not for CD5, CD10, CD23, or cyclin D1, according to flow cytometry. The bone marrow biopsy sample showed nodular proliferation of small to medium-sized abnormal lymphocytes. Based on these findings, the patient was diagnosed as having splenic marginal zone lymphoma, a rare indolent B-cell neoplasm. Although his splenomegaly diminished after eight cycles of weekly rituximab monotherapy, the anemia did not improve, and abnormal lymphocytes remained detectable in his bone marrow. The patient was then treated with bendamustine monotherapy for six cycles, after which the anemia resolved, and he has since been in good condition. Although rare, it is important to consider splenic marginal zone lymphoma during the differential diagnosis of patients with a long history of anemia of unknown cause.

Endoscopic ultrasound-guided placement of plastic vs. biflanged metal stents for therapy of walled-off necrosis: a retrospective single-center series.

BACKGROUND AND STUDY AIMS: Recently, a novel fully covered and biflanged metal stent (BFMS)dedicated to the drainage of walled-off necrosis(WON) was developed. The aim of this study was to retrospectively evaluate the safety, efficacy, and cost performance of drainage of WON using the novel BFMS compared with a traditional plastic stent. PATIENTS AND METHODS: A total of 70 patients with symptomatic WON were treated under endoscopic ultrasound (EUS) guidance. Initial drainage was conducted using the single gateway technique with placement of one or more plastic stents or a single BFMS.If drainage was unsuccessful,direct endoscopic necrosectomy (DEN)was performed. RESULTS: There were no statistically significant differences in rates of technical success, clinical success,and adverse events between plastics stents and BFMS, despite the size of WON in the BFMS group being significantly larger than that in the plastic stent group (105.6 vs. 77.1 mm; P=0.003).The mean procedure times for the first EUS-guided drainage and for re-intervention were significantly shorter in the BFMS group than in the plastic stent group (28.8±7.1 vs. 42.6±14.2, respectively,for drainage, P<0.001; and 34.9±8.5 vs.41.8±7.6, respectively, for re-intervention, P<0.001). There was no statistically significant difference in the total cost between plastic stent and BFMS use in the treatment of WON ($5352vs. $6274; P=0.25). CONCLUSIONS: Plastic stents and BFMS were safe and effective for the treatment of WON. In particular,BFMS placement appeared to be preferable for initial EUS-guided drainage and additional reintervention(e.g. DEN) as it reduced the procedure time. Prospective randomized controlled trials are warranted.

Mid-term outcome of endoscopic sphincterotomy combined with large balloon dilation.

BACKGROUND AND AIM: Endoscopic sphincterotomy (ES) combined with large balloon dilation (ESLBD) can be useful for extracting large and multiple bile duct stones. Although there are many studies on the feasibility and short-term outcome, there are few reports about mid- to long-term outcome after ESLBD. The aim of our study is to prospectively evaluate the mid-term outcome of ESLBD. METHODS: One hundred eighty-three patients who underwent ESLBD between November 2006 and May 2012 were included. The patients were followed up periodically after the procedure until April 2013. Papillary dilation was performed at the time of initial ES or prior ES. Early and late adverse events and stone recurrence were evaluated in this study. RESULTS: The patients' mean age was 76.6 ± 10.7 years. Surgically altered anatomy was present: Billroth I gastrectomy (2), Billroth II gastrectomy (13), and gastrectomy with Roux-en Y reconstruction (18). Seventy-eight (42.6%) patients had periampullary diverticulum. Prior ES had been performed in 40 (21.9%) patients. The mean follow-up period was 43.5 ± 19.7 months (range 11-78). Eight (4.4%) patients had stone recurrence. There was rare stone recurrence after initial ESLBD treatment and native gastrointestinal anatomy. Univariate and multivariate analyses showed that prior ES and previous history of stone recurrence were predictive of stone recurrence (P < 0.001). CONCLUSION: At mid-term outcome, ESLBD is associated with a low rate of recurrent bile duct stones, although long-term follow up is needed.

Effectiveness of the J-Tip Guidewire for Selective Biliary Cannulation Compared to Conventional Guidewires (The JANGLE Study).

BACKGROUND: Wire-guided cannulation has become a common biliary cannulation technique worldwide. Different guidewires with various tip shapes and materials have been reportedly used for wire-guided cannulation. However, there are apparently no studies reporting changes in the biliary cannulation rate according to the type of guidewire used. AIMS: We evaluated the effectiveness of the J-tip guidewire for biliary cannulation. METHODS: We conducted a prospective, multicenter, controlled study involving patients with a native papilla who required biliary cannulation. We allocated the patients to the J-tip guidewire or angled-tip guidewire groups (groups J and A, respectively). If biliary cannulation was not achieved within 10 min, the GW was changed and cannulation was continued. RESULTS: Groups J and A consisted of 66 and 65 enrolled patients, respectively. The biliary cannulation rate with a single guidewire for the first 10 min was 84.8 % (56/66) for group J and 80.0 % (52/65) for group A. The final success rate for biliary cannulation was 100 % in both groups. The mean times necessary for biliary cannulation were 285.8 and 267.6 s in group J and group A, respectively. The incidence rates of complications (i.e., all mild pancreatitis) were 3.0 % (2/66) and 6.2 % (4/65) in group J and group A, respectively. The mean amylase concentrations were 168.0 and 297.7 IU/L in group J and group A, respectively. There were no significant differences in any results between both groups. CONCLUSION: The biliary cannulation rate of the J-tip guidewire was not significantly different from those of standard guidewires.

Efficacy and safety of endoscopic papillary large balloon dilation for large bile duct stones in elderly patients.

BACKGROUND: Minimally invasive interventions for choledocholithiasis are preferable in elderly patients because they tend to have multiple underlying disorders or a decreased activity of daily living. Endoscopic sphincterotomy and endoscopic papillary balloon dilation have been recognized as first-line treatments for choledocholithiasis excluding difficult cases such as large stones or multiple stones. Recently, the safety and efficacy of endoscopic papillary large balloon dilation (EPLBD) for difficult choledocholithiasis cases have been reported, although scarcely in elderly patients. AIMS: To investigate whether EPLBD can be safety and effectively performed in patients aged 75 years or older. METHODS: The medical records of 165 patients who underwent EPLBD from November 2006 to August 2013 were analyzed retrospectively. The patients were divided into 2 groups: Group A (≥ 75 years); Group B (<75 years). RESULTS: Some underlying diseases were significantly more common in Group A than in Group B (P < 0.05). However, there was no significant difference in the success rates in the first session (96.2 vs 95.0 %, P = 0.970) and in the final success rates (100 % in both groups) between Group A and Group B. The adverse event rates (2.9 vs 5.0 %, P = 0.783) and recurrence rates of choledocholithiasis (6.7 vs 10.0 %, P = 0.444) were not significantly different. Regarding patients with an altered anatomy, the EPLBD outcome was not significantly different. CONCLUSION: EPLBD can be safely performed for elderly patients similarly to younger patients.

Clinical evaluation of a prototype multi-bending peroral direct cholangioscope.

BACKGROUND: Although peroral direct cholangioscopy (PDCS) is emerging as an alternative to traditional mother-daughter cholangioscopy, it is associated with high failure rates. The aim of the present study was to evaluate the ability to insert and carry out interventions using a prototype multi-bending PDCS. PATIENTS AND METHODS: Prospective, observational clinical feasibility study was done in 41 patients with a variety of biliary diseases. A multi-bending PDCS prototype was inserted using a free-hand technique, a guidewire alone, or with a 5-Fr diameter anchoring balloon. Diagnostic and therapeutic procedures were carried out. RESULTS: The free-hand direct insertion technique failed in all attempted cases (n = 7). Of the remaining 34 cases, successful rate of PDCS insertion into the distal bile duct was achieved by passing the PDCS over a guidewire alone (n = 6) and/or with a guidewire plus anchoring balloon (n = 28) for an overall successrate of 88.2% (30/34). In 13 (92.9%) patients without an underlying biliary stricture, PDCS insertion proximal to the bifurcation was possible. In 25 cases, biliary interventions were attempted including biopsy (n = 13), stone removal (n = 6), stent removal (n = 1), and intraductal electrohydraulic lithotripsy (n = 2) and were successful in 22 (88%). Other than two patients with procedure-related cholangitis with a mild grade of severity, no complications were observed. CONCLUSIONS: Using a novel multi-bending prototype peroral direct cholangioscope, cholangioscopy had a high diagnostic and therapeutic success rate only when passed over a guidewire and anchoring balloon but not with the free-hand insertion technique. Comparative studies of direct cholangioscopy are warranted.

Successful treatment of chronic disseminated intravascular coagulation using recombinant human soluble thrombomodulin in a dialysis patient with dissecting aortic aneurysm.

A 62-year-old man had a history of acute aortic dissection (Stanford type A) and had been diagnosed with polycystic kidney disease three years earlier, and then developed end-stage renal failure. He was referred with chief complaints of difficult hemostasis and consecutive hemorrhagic episodes at the puncture site of the shunt soon after dialysis introduction. We suspected chronic disseminated intravascular coagulation (DIC) due to mild thrombocytopenia and a fibrinolytic system abnormality. Plasma factor XIII activity was decreased, but no inhibitor was detected. In addition, contrast-enhanced computed tomography showed exacerbation of a dissecting aortic aneurysm. We finally diagnosed chronic DIC and secondary factor XIII deficiency associated with the aortic aneurysm. We selected treatment involving recombinant human soluble thrombomodulin (rTM) because he was on maintenance dialysis and required long-term follow-up bofore the operation. Hemostatic function improved with regular administration of rTM, and was well-controlled preoperatively.

Is the double-guidewire technique superior to the pancreatic duct guidewire technique in cases of pancreatic duct opacification?

BACKGROUND AND AIMS: Pancreatic duct guidewire placement (P-GW) techniques include both the injection cannulation technique with a contrast medium and wire-guided cannulation without contrast injection for selective biliary cannulation; the latter is the so-called "double-guidewire technique" (D-GW). The aim of this study was to compare the outcomes between P-GW and D-GW for biliary cannulation. METHODS: The procedures for biliary cannulation with a naïve papilla were performed in a total of 363 cases. We divided the patients chronologically, according to the time period during which the procedures were performed, into two groups: group A, P-GW performed from March 2008 to June 2009; and group B, D-GW performed from July 2009 to December 2010. The success rates and complication rates were evaluated in each group. RESULTS: Biliary cannulation was successful in 31 (81.6%) patients in the P-GW group and 34 patients (82.9%) in the D-GW group. The onsets of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) occurred in the P-GW and D-GW groups were four (10.5%) and three (7.3%) patients, respectively, and all were mild cases (P = 0.616). The frequency of hyperamylasemia and the serum amylase level tended to be lower in the D-GW group than in the P-GW group (P = 0.213). There was a statistically significant difference on the onsets of PEP in the GW and non-GW groups (P = 0.04, 8.9% and 1.1%, respectively). CONCLUSIONS: Both the D-GW and P-GW techniques were equally effective for difficult biliary cannulation. Furthermore, the complication rates, including PEP, were similar in both techniques. A prospective randomized trial is warranted.

Endoscopic ultrasonography-guided pancreatic duct drainage after failed endoscopic retrograde cholangiopancreatography in patients with malignant and benign pancreatic duct obstructions.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided pancreatic drainage has been advocated as a rescue treatment for management of patients in whom retrograde access to the pancreatic duct (PD) is technically unsuccessful. The aim of the present study was to evaluate the feasibility and efficacy of EUS-guided drainage for failed endoscopic retrograde cholangiopancreatography. PATIENTS AND METHODS: A total of 17 EUS-guided PD drainage (EUS-PD) procedures were carried out in 14 patients (age: mean 64.6 years, range 54-81 years, eight men). RESULTS: The rendezvous technique was successful in 11 of 17 procedures (64.7%). Three of five patients with an unsuccessful rendezvous technique successfully underwent EUS-PD stenting (7-Fr plastic stent [two cases], 5-Fr endoscopic nasobiliary drainage [one case]). In the two remaining patients, puncture and pancreatography were successful; however, antegrade passage of the guidewire failed. CONCLUSION: EUS-guided decompression of PD is a feasible and effective treatment for the management of symptomatic high-pressure PD due to stricture of the PD and/or stenotic pancreatodigestive anastomosis. However, this procedure is technically challenging, has a high rate of complications, and should be done only at tertiary-care centers.

Endoscopic ultrasonography-guided pancreatic duct access: techniques and literature review of pancreatography, transmural drainage and rendezvous techniques.

Endoscopic ultrasonography-guided (EUS)-guided pancreatic interventions have gained increasing attention. Here we review EUS-guided pancreatic duct (PD) access techniques and outcomes. EUS-guided PD intervention is divided into two types, antegrade and rendezvous techniques, following EUS-guided pancreatography. In the antegrade technique, pancreaticoenterostomy is carried out by stent placement between the PD and the stomach, duodenum, or jejunum. Transenteric antegrade PD stenting is conducted by stent placement, advancing anteriorly into the PD through the pancreatic tract. The rendezvous technique is carried out by using a guidewire through the papilla or anastomotic site for retrograde stent insertion. In terms of EUS-guided PD stenting, 11 case reports totaling 75 patients (35 normal anatomy, 40 altered anatomy) have been published. The technical success rate was greater than 70%. Early adverse events, including severe hematoma and severe pancreatitis,occurred in seven (63.6%) of 11 reports. Regarding the rendezvous technique, 12 case reports totaling 52 patients (22 normal anatomy, 30 altered anatomy) have been published. The technical success rate ranged from 25% to 100%. It was 48% in one report that involved more than 20 cases. Once stents were placed, all patients became free of symptoms. Early mild adverse events occurred in four (36.4%) of 11 reports. In conclusion, although it can be risky because of possible serious or even fatal adverse events, including pancreatic juice leakage, perforation and severe acute pancreatitis, EUS-PD access seems to be promising for treating symptomatic pancreatic diseases caused by PD stricture and pancreaticoenterostomy stricture.

Clinical evaluation of a novel lumen-apposing metal stent for endosonography-guided pancreatic pseudocyst and gallbladder drainage (with videos).

BACKGROUND: Tubular plastic and metal stents have inherent shortcomings when used for transenteric drainage of fluid collections. OBJECTIVE: To evaluate a novel lumen-apposing, self-expandable metal stent for EUS-guided drainage of pancreatic pseudocysts and the gallbladder. DESIGN: Retrospective case series. SETTING: Tertiary-care academic medical center. PATIENTS: This study involved 15 patients (median age 54 years) with symptomatic pancreatic pseudocysts who underwent 12 transgastric and 3 transduodenal pseudocyst drainage procedures. Five patients (median age 69.5 years) with acute cholecystitis underwent 4 cholecystoduodenostomies and 1 cholecystogastostomy. INTERVENTION: Stent deployment under EUS guidance, passage of an endoscope through the stent lumen for pseudocystoscopy or cholecystoscopy, transenteric endoscopy-guided interventions including biopsy, necrosectomy, and stone removal. MAIN OUTCOME MEASUREMENTS: Technical and clinical success. RESULTS: All stents were successfully deployed without complication, with a median time to removal of 35 days. All pseudocysts resolved after a single drainage procedure. One stent migrated into the stomach, and the remaining 14 were found to be patent at the time of removal. There was no pseudocyst recurrence during the 11.4-month median follow-up period. One gallbladder stent remains indwelling and fully patent at 12 months. Resolution of acute cholecystitis was observed immediately after stent implantation. No recurrence of symptoms was observed during a median follow-up period of 9 months. LIMITATIONS: Retrospective study, small sample size, lack of control patients. CONCLUSION: Transenteric drainage of pancreatic pseudocysts and the gallbladder by using a novel, lumen-apposing, metal stent was accomplished with high technical and clinical success in this pilot observational study. Further studies are warranted.

Novel biopsy forceps for diagnosis of biliary tract diseases during endoscopic retrograde cholangiopancreatography: a prospective comparative study with 90° adjustable and conventional biopsy forceps.

BACKGROUND/AIMS: Recently, controllable biopsy forceps (MTW, D°sseldorf, Germany) have been developed. This biopsy forceps were 90° adjustable. In the present study, the feasibility and efficacy of the controllable biopsy forceps were compared with those of conventional biopsy forceps in patients with biliary tract disease. METHODOLOGY: A total of 27 patients with biliary tract lesions were enrolled. We evaluated the procedure time, the sample tissue size and the diagnostic accuracy. In addition, the physicians performing the procedure rated their impressions about operability into 3 classes: excellent, fair and poor. RESULTS: The sensitivity in distinguishing benign from malignant lesions was 71.4% (15/21) for the 90° adjustable type and 66.7% (14/21) for the conventional type. The accuracy rate was 77.8% (21/27) for the 90° adjustable type and 74.0% (20/27) for the conventional type. In terms of operability as rated by each physician, the 'excellent' rate was given more frequently to the 90° adjustable type 25.9% than for the conventional type 11.1% (p=0.047). CONCLUSIONS: This preliminary study showed that controllable biopsy forceps compared to conventional type biopsy forceps, despite a larger diameter, enables biopsy in a similar procedure time and its ease of use was rated better.

Novel protective lead shield and pulse fluoroscopy can reduce radiation exposure during the ERCP procedure.

BACKGROUND/AIMS: ERCP-related procedures involve radiation exposure of patients and medical staff. We developed a novel protective lead shield which is attached around the fluoroscopy generator. Here we examine levels of radiation exposure to patients, endoscopists and assistants, and evaluate the usefulness of the newly designed protective shield. METHODOLOGY: Four-hundred and seventy-one ERCP procedures were performed from April 2006 to April 2007. At first, we compared the radiation dose of consecutive fluoroscopy conditions with pulse fluoroscopy of 15 per second and then the radiation dose with and without the protective shield. Next, we measured the radiation exposure of endoscopists and assistants in the clinical setting monitored by digital dosimeter during ERCP procedure. RESULTS: The radiation dose was the most at the 45° direction. Using pulse fluoroscopy of 15 per second the radiation dose of patients and endoscopists decreased by about half. Using both pulse fluoroscopy of 15 per second and the protective shield, the radiation dose at the endoscopist's position was reduced up to 97%. The total fluoroscopy time was 5851 minutes in the 471 ERCP cases. Using pulse 15 and the protective lead shield, the radiation exposure dose of one endoscopist and two assistants were 2430.8, 2673.9 and 1375.0µSv, respectively. CONCLUSIONS: Novel protective lead shield in combination with pulse fluoroscopy can significantly reduce the radiation exposure leading to avoid unnecessary radiation exposure to patients and medical staff.

Contrast-enhanced ultrasonography in the diagnosis of gallbladder disease.

BACKGROUND/AIMS: The aim of our study was to evaluate the enhancement patterns of gallbladder disease using contrast-enhanced ultrasonography (CE-US) with the contrast agent levovist. METHODOLOGY: The subjects were 42 patients, of whom 25 had gallbladder cancer, 2 had adenoma, 5 had adenomyomatosis, 5 had cholesterol polyps and 5 had debris. We assessed the enhancement patterns of each case using CE-US with levovist and classified these patterns into 6 types: diffuse, scattered, branched, linear, homogeneous and unenhanced. RESULTS: The enhancement of gallbladder cancer revealed various patterns. Only 4 malignant cases showed branched patterns. We speculated that branched patterns in the present study were possibly the characteristic of malignancy. CE-US easily distinguished a small polypoid lesion from debris. Using CE-US, we visualized the shape of the gallbladder cancer lesions and some areas of direct invasion to the liver, as well as metastasis. CONCLUSIONS: CE-US is a minimally invasive diagnostic technique that is useful in visualizing not only the shape of the lesion and some areas of the direct invasion to the liver, but also metastasis. The above findings suggest that imaging using a contrast agent could lead to improvements in the diagnosis of gallbladder lesions.

Long- and short-type double-balloon enteroscopy-assisted therapeutic ERCP for intact papilla in patients with a Roux-en-Y anastomosis.

BACKGROUND: There have been a few previous reports on attempted double-balloon endoscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) in patients with Roux-en-Y anastomosis and an intact papilla. This study was designed to evaluate the usefulness of DBE-assisted ERCP in patients with Roux-en-Y anastomosis and an intact papilla of Vater. METHODS: Thirteen DBE procedures were performed in nine patients who had undergone Roux-en-Y reconstruction combined with eight total gastrectomies and one partial gastrectomy. Both short-type and long-type DBE were used. Long-type DBE was replaced with a conventional forward-viewing upper endoscope after reaching the papilla. Technical success rate, measurement of procedure times, and adverse events were evaluated in the retrospective study. RESULTS: In all cases, the scopes could reach the papilla. The mean time required to reach the papilla was 48 (range, 13-90) min. There was a statistically significant difference with the short and long scope (29.0 ± 19.2 min vs. 64.8 ± 24.7 min, respectively; P = 0.044). The success rate of bile duct cannulation, resulting in achieving therapeutic ERCP on the first session was 66.7% (6/9). The mean procedural time in the successful cases was 128 (range, 47-183) min. Finally, therapeutic ERCP was achieved in all nine cases. There was one adverse event in which retroperitoneal perforation during lithotripsy, but that was successfully treated by conservative therapy alone. CONCLUSION: DBE-assisted ERCP seems to be a promising option to perform therapeutic ERCP for intact papilla in patients with a Roux-en-Y anastomosis.

A multicenter prospective study of the short-term outcome of a newly developed partially covered self-expandable metallic biliary stent (WallFlex(®)).

BACKGROUND: Self-expandable metallic stent (SEMS) placement is a widely used, effective therapy for unresectable malignant stricture of the lower bile duct. AIMS: We evaluated the short-term outcome of the newly developed WallFlex(®) Biliary RX Partially Covered Stent in patients with malignant lower and middle biliary stricture in five tertiary referral centers. METHODS: The subjects of this study were 52 patients in whom WallFlex(®) Biliary RX Stents were inserted into the bile duct for malignant stenosis of the middle and lower bile duct at five medical facilities between April 2009 and November 2009. RESULTS: The stent placement success rate was 100%. Effective biliary decompression was achieved in all patients. The incidence of early complications was 7.7% (4/52). Stent occlusion occurred in two patients (3.8%) (one dislocation, one migration); cholecystitis occurred in two patients (3.8%). Neither acute pancreatitis nor stent kinking in the bile duct occurred. CONCLUSIONS: The present results revealed that the new WallFlex(®) Biliary RX Partially Covered SEMSs were useful for the short-term relief of biliary obstruction due to unresectable distal biliary malignancies.

Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARß activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists. METHOD: Lipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs. RESULTS: We observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα. CONCLUSIONS: Phytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.

Endoscopic ultrasonography-guided fine needle aspiration biopsy in a patient with prior Billroth II gastrectomy.

Endoscopic ultrasonography-guided fine needle aspiration biopsy (EUS-FNA) is a safe and accurate procedure for the diagnosis of pancreatic lesions. However, in general, surgically altered anatomy excluding Billroth I gastrectomy is considered a relative contraindication to EUS-FNA. Herein, we described a successful case of EUS-FNA in a patient with prior Billroth II gastrectomy. A 78-year-old man, who had previously undergone Billroth II gastrectomy for duodenal ulcer, undertook EUS-FNA using a curved linear echoendoscope. An echoendoscope was advanced into the duodenum and EUS-FNA could be carried out using a 22-gauge needle without procedure-related adverse event.

Histological diagnosis by EUS-guided fine-needle aspiration biopsy in pancreatic solid masses without on-site cytopathologist: a single-center experience.

There are few reports on the histological diagnostic ability of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) in a large-series of pancreatic masses. In the present study therefore we retrospectively evaluated the histological diagnostic ability of EUS-FNA in pancreatic masses without on-site cytopathologist. In 355 patients with pancreatic solid masses, EUS-FNA was carried out. EUS-FNA histology showed accuracy, 90.7%; sensitivity, 89.5%; specificity, 95.6%; positive predict value, 98.8%; negative predict value, 68.8% by intention-to-treat analysis. Except for 10 with inadequate materials, EUS-FNA histology showed accuracy, 93.3%; sensitivity, 91.8%; specificity, 100%; positive predict value, 100%; negative predict value, 77.6%. The mean number of puncture was 2.88 (range 1 to 8). There was two (0.6%) procedure-related bleeding. In conclusion, diagnostic ability of EUS-FNA by histological materials was similar to previous literature on the EUS-FNA without on-site cytopathologist.