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The purpose of this study was to evaluate the palatability of dry syrups for pediatric use by human gustatory sensation testing and the artificial taste sensor. The bitterness intensities of dry syrups mixed with various beverages were also evaluated using the taste sensor. Twenty dry-syrup formulations of antibacterial and anti-allergic drugs containing bitter active ingredients, frequently used in pediatric medicine in Japan, were selected for testing. The main factors influencing palatability were determined by factor analysis of data from human gustatory sensation testing using the semantic differential method. It was shown that the bitterness intensity of dry syrups in water could be predicted by the artificial taste sensor. The influence of different beverages (orange juice, milk or cocoa) mixed with the dry syrups was evaluated using the artificial taste sensor. Taste and texture were found to be the principal factors influencing the palatability of dry syrups. While the bitterness intensities of some dry syrups were increased by mixing with orange juice, the bitterness intensities of most dry syrups were decreased by mixing with milk or cocoa. This suggests that one or more constituents of milk or cocoa may reduce the bitterness intensities of dry syrups.

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.

Background Recently, a new digital cholangiopancreatoscopy (DCPS) has been developed. The aim of this study is to retrospectively evaluate the utility of new DCPS in patients with pancreaticobiliary diseases. Methods Digital cholangiopancreatoscopy was used in 26 patients (16 men) with pancreaticobiliary diseases that could not be diagnosed and treated by standard endoscopic retrograde cholangiopancreatography (ERCP). The procedures included DCPS-guided tissue sampling and interventions. Technical success and adverse events were evaluated. Results Among the 26 patients, 19 patients were classified for diagnostic purposes and seven for therapeutic purposes. The detailed breakdown of the particular conditions and numbers of patients was as follows: indeterminate bile duct (BD) lesion, indeterminate pancreatic duct (PD) lesion, lithotripsy by yttrium aluminum garnet-laser or electrohydraulic lithotripsy, removal of migrated BD stent and PD stent, and guidewire passing across the biliary stricture. The overall technical success rates of visualizing the target lesions and therapeutic interventions were 100% and 85.7%, respectively. The incidence of procedure-related adverse events among the patients was 7.7% (2/26). Cholangitis developed in one of the patients and post-endoscopic sphincterotomy bleeding in one patient. All adverse events were successfully treated by conservative therapy. Conclusion Digital cholangiopancreatoscopy has a high potential for providing an accurate diagnosis and facilitating therapy in patients with pancreaticobiliary diseases.

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

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.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.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, P0.001; and 34.9±8.5 vs.41.8±7.6, respectively, for re-intervention, P0.001). 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).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.

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. To investigate whether EPLBD can be safety and effectively performed in patients aged 75 years or older. 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 (

Primary plasma cell leukemia (PPCL) is a rare disease that progresses rapidly. In such cases, it is difficult to achieve remission, and early intensive chemotherapy is recommended. We herein describe the case of a 76-year-old man with PPCL complicated by renal failure and pulmonary hypertension. Bortezomib/dexamethasone induction therapy with lenalidomide was administered in association with continuous hemodiafiltration (CHDF). Complete remission was achieved after a single course of treatment, resulting in the cessation of CHDF. With the patient in remission, the administration of beraprost and bosentan resulted in improvements in the pulmonary hypertension. The results of this case report support the use of bortezomib/lenalidomide/dexamethasone combination therapy as an effective treatment for elderly PPCL patients with various complications.

Background and study aims: 19-gauge (19G) needles are used for EUS-guided tissue acquisition and interventions. The aim of the current study was to compare the functional characteristics of 19G EUS needles by means of using various echoendoscopes in a bench simulator. Methods: The angles achieved for 19G needles (EchoTip: ET-19G, EchoTip Flex: ExF-19G, Expect: Ex-19G, and ProCore: PC-19G) and for the distal tip of the echoendoscope were evaluated for maximal angulation settings of the distal tip and the elevator. Also the resistance to advancement of the 19G needles at these endoscope settings was assessed. All evaluations were done with endoscopes in a straight and in a curved position. Results: There was no large discrepancy for scope and needle angles among all echoendoscopes except for the slim Pentax scope (EG-3270UK). The ExF-19G and PC-19G needles showed better optimal angles in various conditions compared to standard 19G needles. In straight scope position, out of the 20 conditions (5 endoscopes × 2 positions of the distal tip × 2 elevator positions) the numbers of optimal angulations achieved for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 11 /20 (55 %), 20 /20 (100 %), 14 /20 (70 %) and 18 /20 (90 %), respectively. However, regarding resistance, it was impossible to advance theneedle with 14 /20 settings (70 %) for the Ex-19G, 3 /20 (15 %) for the ExF-19G, 10 /20 (50 %) for the ET-19G and 7 /20 (35 %) for the PC-19G. When the scopes were bent, with regard to the force needed to advance the needle, the numbers of optimal settings, for the Ex-19G, ExF-19G, ET-19G, and PC-19G, were 1 (5 %), 13 (65 %), 6 (30 %) and 8 (40 %), respectively. The mean maximum resistance to advancement was less for the ExF-19G than for the other needless in almost all scope and angle conditions (p

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 naive 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.

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 nasobiliarydrainage [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 (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.

Endoscopic ultrasonography-guided biliary drainage (EUS-BD) has been carried out as an alternative to the percutaneous or surgical approach when endoscopic retrograde cholangiopancreatography fails. However, there is no standard technique or device for EUS-BD. In this review, we focus on how we choose the stents and described our tips on this EUS-BD technique. The plastic stent (PS) and the self-expandable metallic stent (SEMS) are used for EUS-BD. The latter is further divided into the fully covered SEMS (FCSEMS), partially covered SEMS (PCSEMS), and uncovered SEMS (UCSEMS) types. Although PS is not expensive, the duration of stent patency is short. SEMS is expensive but the duration of stent patency is long. With UCSEMS, basically there is no stent malpositioning; however, if the gap between the bile duct and the GI tract becomes displaced, bile leakage from the mesh of the stent is likely to occur. Though there is no bile leakage with FCSEMS, the side branch of the bile duct may become occluded, and migration and dislocation sometimes occur. PCSEMS is basically similar to FCSEMS. When EUS-BD was first developed, drainage by PS was common, although reports on drainage by SEMS have increased recently.

Traditionally, either surgical or percutaneous drainage is recommended for liver abscess. Recently, several endoscopists have reported the endoscopic ultrasound (EUS)-guided liver abscess drainage. Herein, we report a case of tuberculous liver abscess in which endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for the diagnosis and therapy. A 78-year-old woman suffered from continuous epigastric pain and fever up. Computed tomography (CT) showed a 70 mm multilocular and multiseptate cystic lesion around the head of pancreas and caudate lobe of the liver. After confirming liver abscess by EUS-FNA, EUS-guided liver abscess drainage was carried out. Finally, a 7 Fr straight stent and a 5 Fr nasocystic catheter were inserted into the cyst. Four weeks later, we found that cultured microorganism obtained using drainage catheter was Mycobacterium tuberculosis. Although he was doing well during 5 days after the procedure, CT showed the size of another abscess increased. Then, additional EUS-guided abscess drainage was carried out at the body of the stomach into the abscess of the left lobe. Two weeks later, CT showed disappearance of abscesses. Then, she discharged with the internal stent still in place.

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.

Pancreatic carcinoma has one of the poorest prognoses among malignant tumors. Many pancreatic carcinoma patients who undergo common treatments, such as surgery, radio-chemotherapy and chemotherapy, gained little benefit because of the histological characteristics.HIFU is a new technique of noninvasive treatment for unresectable pancreatic carcinoma. HIFU has the ability to ablate the deep tissues inside body from an external source using high-intensity focused ultrasound. The effects of HIFU can result in cell destruction and tissue necrosis.Results from study in China in 251 patients with advanced pancreatic carcinoma suggested that HIFU treatment could reduce the size of tumors without causing complications and prolong survival. Moreover, according to some reports from China, HIFU treatment is suggested to be useful as the one of palliative treatments for unresectable pancreatic carcinoma. Our case of HIFU therapy for pancreatic carcinoma is presented including pathological findings in this paper. The results suggested that HIFU treatment might be effective in controlling local tumor.HIFU therapy may have the possibility of becoming one of the combination therapies for treating pancreatic carcinoma in the future.

Background Extraction of bile duct stones in patients who have undergone Roux-en-Y anastomosis can be challenging. Recently, large balloon dilation following endoscopic sphincterotomy has been shown to be useful for the removal of bile duct stones. Aim We retrospectively evaluated the feasibility and safety of endoscopic sphincterotomy large balloon dilation for the removal of bile duct stones in patients with Roux-en-Y anastomosis. Methods Large balloon papillary dilation following EST for the removal of bile duct stones was performed on the intact papilla in 15 patients with Roux-en-Y anastomosis at our institution. When we could not use the long-type accessories, a conventional forward-viewing upper endoscope passed through the over tube of the single-balloon or double-balloon enteroscope for the use of short-type accessories. Following endoscopic sphincterotomy, a large balloon catheter was positioned across the main duodenal papilla. The size of large balloon used ranged from 15 mm to 20 mm. Results Complete clearance of bile duct stones was achieved in all cases in the initial session without any adverse events. A mechanical lithotriptor for crushing stones was used in one patient (6.7%). Conclusion Large balloon papillary dilation following EST appears to be an effective and safe treatment for difficult-to-remove bile duct stones in patients with Roux-en-Y anastomosis .

Self-expandable metallic stent (SEMS) placement is a widely used, effective therapy for unresectable malignant stricture of the lower bile duct.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.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.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.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.

膵疾患において血流動態を加味したCE-USは，鑑別診断および進展度診断に有用とされている．しかし高音圧性の超音波造影剤Levovist®を用いたCE-USでは限界があり問題点も明らかとなってきた．そのためより精密な描出や評価が可能となる第2世代低音圧性超音波造影剤Sonazoid®や新しく開発された造影超音波手法を用い，これまでのLevovist®を用いたCE-USとの比較検討をおこなった．結果では，総じてSonazoid®がLevovist®より緻密な画像が得られ，これまで以上に正確な染影評価が可能であった．Sonazoid®を使用することでLevovist®では映像化が困難であった微小血管内でのマイクロバブルの細かい動きをリアルタイムに繰り返し可視化することができた．特に悪性腫瘤では腫瘤内部の微小血管に一致してマイクロバブルが不規則に揺れ動く，いわゆるirregular rolling signが特徴的で良悪性の鑑別に有用であった．膵疾患においてSonazoid®を用いたCE-USは従来のLevovist®以上に診断能の向上が得られ，鑑別診断に有用であった．

Endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) has been developed as an alternative drainage method in patients with acute cholangitis. Here, we describe two successful EUS-GBD cases and review the literature on this topic.EUS-GBD was conducted using a curved linear array echoendoscope and a 19-gauge needle.A 7-Fr double pigtail stent was successfully placed transgastrically in one patient and transduodenally in the other patient, without any serious early adverse events in either patient. No late complications or relapse of acute cholecystitis have been seen during the 3- to 6-month follow-up period.EUS-GBD holds high potential as an alternative gallbladder decompression procedure. However, because current experience is limited, multicenter trials for the accurate evaluation of this procedure appear to be necessary in the near future.

Extraction of large bile duct stones in patients who have undergone a Billroth II (B-II) gastrectomy can be challenging. Recently, a large balloon dilation performed after endoscopic sphincterotomy (ESLBD) was useful for the removal of large bile duct stones. The aim of our study was to evaluate the feasibility and safety of ESLBD for removal of bile duct stones in patients who have undergone a B-II gastrectomy. ESLBD for removal of bile duct stones were performed in 11 patients with a B-II gastrectomy at Tokyo Medical University Hospital. Immediately after EST, a large balloon catheter (maximum diameter 15 mm, 18 mm, or 20 mm) was passed over the guide-wire and positioned across the main duodenal papilla. Maximum stone size (short diameter) ranged from 7 to 30 mm with a median of 13.5 mm. The number of stones was 1-26 with a median of 4.8. The common bile duct diameter was 10 mm to 30 mm with a median of 18.1 mm. A mechanical lithotripter for crushing stones was used in two patients (18%). Papillary balloon dilation using variously sized balloons was performed in addition to endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in all cases at one session. There were no procedure-related adverse events such as acute pancreatitis or retroperitoneal perforation. ESLBD appears to be an effective and safe treatment for removal of difficult bile duct stones in patients who have undergone a B-II gastrectomy.

Endoscopic ultrasonography-guided biliary drainage (EUS-BD) has been developed as an alternative drainage method in patients with obstructive jaundice. EUS-BD is divided into EUS-guided choledochoduodenostomy (EUS-CDS), EUS-guided hepaticogastrostomy (EUS-HGS) and EUS-guided gallbladder drainage (EUS-GBD). The aim of this review is to focus on the current status and limitations of EUS-BD. A systematic review was performed to evaluate EUS-BD. MEDLINE, EMBASE and manual searches were performed to identify the pertinent English language full articles. The high success rate without fatal adverse events for EUS-CDS (93%; 28/30) and EUS-HGS (97%; 28/29) suggest the feasibility and safety of the procedures in high-volume endoscopic centers adopting various procedural techniques. Although the number of reported cases was very small, the success rate of EUS-GBD was high (100%; 14/14), without serious adverse events. Although all procedures require further assessment in a larger cohort of patients, including comparative studies between EUS-CDS or EUS-HGS versus PTBD, and EUS-GBD versus PTGBD, EUS-BD may be a promising procedure for the treatment of obstructive jaundice. However, dedicated devices for EUS-guided drainage are needed for reliable procedures.

We sought to evaluate the safety, efficacy, and feasibility of endoscopic sphincterotomy plus large balloon dilation (ESLBD) and to compare procedural time and fluoroscopy time of ESLBD with those of endoscopic sphincterotomy (EST) alone for patients with large bile duct stones.Retrospective analysis.A total of 101 patients with large bile duct stones were treated: 53 were treated by ESLBD and 48 with EST alone. ESLBD resulted in similar outcomes in overall successful stone removal (100% vs. 97%) and complications (4% vs. 6%); however, although the rate of complete stone removal in the first session using ESLBD tended to be higher than when EST alone was used, it was not statistically significant (96% vs. 85%, P=0.057). Mechanical lithotripsy was required significantly more often in the EST group compared to the ESLBD group (25% vs. 6%, P0.01). Total procedure time in the ESLBD group was significantly shorter than that of the EST group (32 vs. 40 min, P0.05). Total fluoroscopy time in the ESLBD group was significantly shorter in the EST group (13 vs. 22 min, P0.05).ESLBD is an effective and safe treatment in patients with large bile duct stones. In addition, ESLBD appears to decrease procedure time and fluoroscopy time and reduce the need for mechanical lithotripsy as compared to EST alone.

Background In the clinical setting, endosonographers acknowledge that not only the size and characteristics of EUS-guided FNA needles but also several conditions affect the acquisition of adequate samples. Objective To compare the characteristics of the 19-gauge Tru-cut, 19-gauge aspiration, 22-gauge aspiration, and 25-gauge aspiration EUS needles under several conditions by using a bench simulator designed to provide standardized, reproducible, comparative performance data in combination with evaluation by 3 endosonographers of needle-insertion resistance. Design Laboratory simulations that compare resistance to needle advancement under several conditions (straight and angulated endoscope position, endoscopic tip angulation, and the use of the elevator) by using both diagnostic and therapeutic EUS scopes. These varied conditions cause a range of resistance to the advancement of the needle through the endoscope. Setting Research laboratory. Main Outcome Measurement The mean (SD) for advancement resistance (N) to each EUS needle. Needle resistance was evaluated individually by endosonographers and divided into 5 levels (0 [no resistance] to 5 [impossible for needle to be advanced]). Results Endosonographers concluded that the needle-advancement resistance was moderate with a pressure resistance to the needle of 5 N or more and high at 8 N or more, and that it was impossible to advance the needle when the resistance to it was 11 N or more. Instrumentational evaluation showed that, with the 25-gauge and 22-gauge needles, needle resistance was approximately less than 2 N and 3 N, respectively. In the straight endoscope position, the 19-gauge aspiration or Tru-cut needle resistance when using upward angulation of the endoscope or the elevator was more than 8 N and 10 N, respectively. In the angulated endoscope position, the resistance to the 19-gauge aspiration or Tru-cut needle when using upward angulation was more than 10 N and 20 N, respectively. Limitations All data were collected ex vivo, and clinical validity remains to be determined. Conclusions The 22-gauge or 25-gauge EUS-guided FNA needles are suitable for insertion into the target regions if tight angulation is necessary.

Background In patients with acute cholecystitis and at high risk for surgery, decompression of the gallbladder by percutaneous transhepatic gallbladder drainage (PTGBD) or aspiration (PTGBA) is needed as salvage therapy. However, we sometimes encounter patients in whom puncture cannot be performed for several reasons. Recently, endoscopic transpapillary gallbladder drainage (ETGD) has been reported to be safe and effective for acute cholecystitis. Objective Our purpose was to evaluate the clinical efficacy and safety of ETGD for acute cholecystitis in which a percutaneous transhepatic approach is contraindicated or anatomically impossible. Design Retrospective case study. Setting This procedure was performed in Tokyo Medical University Hospital. Patients Forty-three patients with acute cholecystitis, including 32 patients taking anticoagulation or antiplatelet drugs, 4 cases of Chilaiditi syndrome, 2 each of acute leukemia, marked ascites, and anatomic abnormality, and 1 case of hemophilia A. Intervention All patients underwent ETGD. A 5F nasobiliary-drainage catheter was placed into the gallbladder. In case of failed ETGD, PTGBD or PTGBA was performed subsequently. Main Outcome Measurement Efficacy and safety of this technique. Results ETGD was achieved in 36 patients (84%) without any serious procedure-related complications. A clinically favorable response for ETGD was seen in 35 patients (97%). In 7 patients in whom ETGD was unsuccessful and 1 patient in which it was ineffective, a percutaneous transhepatic approach was performed with severe hemorrhage biloma in the former and uncontrolled hemorrhage cholecystitis, leading to death in the latter. Limitations Difficulty of maneuvering the guidewire and drainage tube into the gallbladder. Conclusions Although comparative studies are needed to define the appropriate role of ETGD and percutaneous transhepatic approach, ETGD can be useful in patients with acute cholecystitis in which a percutaneous transhepatic approach is contraindicated or anatomically impossible.

Background Endoscopic nasobiliary drainage (NBD) for the treatment of acute cholangitis is an accepted method. A recently developed ultrathin transnasal videoendoscope is minimally invasive, even for patients who are critically ill. Objective To evaluate the clinical efficacy and safety of 1-step NBD by transnasal videoendoscopy (TNE). Design Prospective case study. Setting This study was performed at Tokyo Medical University Hospital. Patients Twenty patients with acute cholangitis who had previously undergone an endoscopic sphincterotomy (ES); including 10 with bile-duct stones, 8 with pancreatic cancers, 1 with chronic pancreatitis, and 1 with benign biliary stricture, were enrolled in this study. An indwelling self-expandable metallic stent (SEMS) was placed in all patients with pancreatic cancers. Intervention All patients underwent NBD via front-viewing TNE. A 5F NBD catheter was placed into the bile duct. Main Outcome Measurement The efficacy and safety of this technique. Results The transnasal insertion of TNE was feasible in all patients, and none had epistaxis. Abdominal pain, fever, and jaundice were improved at 24 hours after the procedure in the majority of patients. The mean procedural time was 18.1 minutes. One patient pulled out the NBD catheter. None of the patients died. TNE-NBD was achieved in 19 patients (95%). Limitations Maneuverability of the TNE, limited to patients with a previous ES or the placement of an SEMS. Conclusions NBD that uses TNE may be a useful and novel technique for the treatment of acute cholangitis in patients with previous ES.

It has been reported that circulating tumor cells (CTCs) can be used to predict survival in metastatic breast cancer. In this preliminary study, we examined the level of CTCs in pancreatic cancer (PC) patients to elucidate whether we could predict survival in PC. The eligible subjects, at Tokyo Medical University Hospital, were 26 patients with PC, 11 with chronic pancreatitis, and 10 healthy volunteers. Three PC patients underwent surgery, 18 patients (who were stage IV) were treated with gemcitabine (GEM), and 5 patients received best supportive care (BSC). The CTC count was 1/7.5 ml blood or higher (defined as positive) in 11 of the 26 patients (42%; mean, 16.9/7.5 ml blood; range, 1-105/7.5 ml blood). Gemcitabine was administered to 6 of the 11 CTC-positive patients (3.8 courses on average). The treatment was continued for more than three courses in 2 patients, in both of whom the CTC count was only 1/7.5 ml blood. Operation was performed in 1 of the 11 CTC-positive patients. The remaining 4 patients of the 11 CTC-positive patients received only BSC. CTC was negative in 15 patients with PC (stage II, 1; stage III, 1; stage IVa, 7; and stage IVb, 6) and in the subjects with benign conditions. The median survival times (MSTs) of the CTC-positive and-negative patients were 110.5 and 375.8 days (P < 0.001). When the analysis was limited to the 14 stage-IVb patients, the MSTs of the CTC-positive and-negative patients were 52.5 and 308.3 days (P < 0.01). The present study demonstrated that the detection of CTCs in peripheral blood may be useful to predict prognosis in patients with PC.

体外式超音波検査法による胆膵疾患の基本的な描出法と注目すべき所見について解説した．肝内胆管の描出には肝内胆管がグリソン鞘内で門脈と並走していることを念頭に置く．カラードプラ法を用いることで門脈と胆管の鑑別は容易となる．肝内胆管病変では肝内胆管拡張と肝内腫瘤に着目する．肝外胆管描出は右肋弓下縦‐斜走査で肝門部の門脈を指標にしてその腹側に描出される管腔を見つける．この際にもドプラは有用である．胆管を描出後長軸に胆管が描出出来るようにプローブを微調整して下部胆管へとスキャンする．左側臥位からの描出や膵内胆管の短軸像を描出した後に胆管を長軸にして下部胆管を描出する方法も時に有用である．肝外胆管では胆管拡張，内腔の病変，および胆管壁に注目して所見を読み取る．胆嚢の描出は肝十二指腸間膜に連続した胆嚢床をメルクマールとする．胆嚢頸部と底部は見落としやすいので特に注意する必要がある．肝外胆管同様左側臥位での観察が有効である．観察時には胆嚢の大きさ，内腔，および胆嚢壁に注目する．膵臓描出の基本となる横走査では脾静脈を指標としてその腹側の膵頭体尾部を長軸に観察する．吸気時には肝臓をウインドウにして描出するが，呼気時の方がよく描出されることが多い．横走査では膵尾部の脾門部付近では不十分なことが多く，左肋間からの描出が有用である．描出にあたっては膵臓の大きさ，膵管拡張，腫瘤に注目する．

Background Narrow-band imaging (NBI) makes it possible to emphasize the imaging of certain features, such as mucosal structures and mucosal microvessels in GI-tract diseases. Recently, video peroral cholangioscopy (POCS) was developed as a diagnostic modality for better visualization of bile-duct lesions; however, there is no report on POCS by using NBI. Objective To evaluate the clinical usefulness of POCS by using NBI for the diagnosis of biliary-tract diseases. Design Prospective case study. Setting This procedure was performed at Tokyo Medical University Hospital. Patients Twelve consecutive patients with biliary-tract diseases, including 7 bile-duct cancers and 5 benign biliary diseases, which revealed 6 bile-duct strictures and 6 filling defects by ERCP. Intervention All patients underwent POCS by using NBI. Main Outcome Measurement Efficacy and safety of this technique. Results Twenty-one lesions were evaluated by using POCS with conventional white light imaging and NBI. Although visualization of only 2 lesions (9.5%) was "excellent" by conventional observation, visualization of 12 lesions (57.4%) was "excellent" by NBI observation. Identification of the surface structure and vessels of the lesions by NBI observation was significantly better than with conventional observation ( P P Limitations Maneuverability and fragility of POCS. The current POCS is not equipped with magnification. Conclusions POCS by using NBI may be helpful for the observation of both fine mucosal structures and tumor vessels.

Background It is very important to determine the extent of intraductal mucinous neoplasms (IPMNs), because this can greatly affect the determination of the indications of surgery. Peroral pancreatovideoscopy (POPS) has been recognized as a new diagnostic tool for clear imaging of IPMN. Recently, narrow-band imaging (NBI) has made it possible to emphasize certain image features, such as mucosal structures and capillary vessels. Objective To evaluate the clinical usefulness of POPS by using NBI for the diagnosis of IPMN. Design Case reports. Setting This procedure was performed at Tokyo Medical University Hospital. Patients Three patients with IPMN. Intervention All patients underwent POPS with NBI. Main Outcome Measurement Efficacy and safety of this technique. Results POPS with NBI was performed in 3 patients, without procedure-related complications. Identification of the surface structure and the capillary vessels by NBI observation was better than by conventional observation. Furthermore, NBI identified skip tumor lesions in the tail of pancreas, which were not detected by conventional POPS. Limitations Because none of the patients in the 3 cases underwent surgical resection, a comparison to clarify total agreement between the preoperative POPS findings and the resected specimen was not possible. Conclusions POPS with NBI may facilitate the observation of both fine mucosal structures and capillary vessels in patients with IPMN, although further study is necessary to fully establish the clinical benefit.

Narrow band imaging (NBI) makes it possible to emphasize the imaging of certain features such as mucosal structures and mucosal microvessels in gastrointestinal tract diseases. Recently, video peroral cholangioscopy (POCS) has been developed as diagnostic endoscopy for better observation of bile duct lesions, but there is no report on POCS using NBI. Herein is described the efficacy of POCS using NBI for the observation of both fine mucosal structures and tumor vessels, resulting in correct target biopsy in patients with biliary tract diseases.

Post endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis is the most common complication of ERCP, which can occasionally become serious or fatal. This preliminary study was to prospectively evaluate the efficacy of a temporary unflanged pancreatic duct stent (PS) to prevent post-ERCP pancreatitis.A total of 64 patients were randomly divided into a control group, which did not undergo stenting, and a stent group. The stent used was a 5-Fr pigtail PS without an inner flange.Placement of an unflanged PS was successful and without complications in all 32 patients. The rates of hyperamylasemia were 50.0% and 34.4% in the control and stent groups, respectively (P0.05), and the mean serum amylase levels were 456.2 and 257.9 IU/l, respectively (P = 0.035). The overall rates of post-ERCP pancreatitis diagnosed according to Cotton's criteria were 12.5% and 3.1% in the control and stent groups, respectively (P0.05). The severity of pancreatitis was severe in one patient, moderate in one, and mild in two in the control group, whereas in the stent group, the single case of pancreatitis was mild.Placement of an unflanged 5-Fr PS may be useful in preventing post-ERCP pancreatitis.

We used a shotgun DNA microarray strategy for gene expression analysis in brewing lager yeast for the first time. We constructed a random genomic library from a bottom-fermenting (lager) yeast strain, Weihenstephan 34/70, which is widely used in lager beer brewing. A DNA fragment size of ≈2.5 kbp was chosen, and 20,160 clones from the genomic library were printed on the shotgun DNA microarray. The gene expression analysis was carried out with total RNA extracted from lager yeast strains for a series of fermentation trials. Among the 7,636 spots that showed more than the limit of detection, 207 were selected as showing significant expression changes. In all, 37 spots were first repressed and then induced, and 62 spots were first induced and then repressed. Those spots were sequenced, annotated, and categorized into four clusters composed of the following sets of genes: 1) significantly induced, 2) significantly repressed, 3) first repressed and then induced, and 4) first induced and then repressed. These different patterns of expression for genes related to the fermentation process have been discussed. Therefore, we have shown that the shotgun DNA microarray technology is a very useful tool for accomplishing gene expression studies with lager yeast strains.

Aim: To evaluate prospectively the efficacy of endoscopic transpapillary naso-gallbladder drainage (ETGBD) after endoscopic sphincterotomy (ES) in patients with acute cholecystitis with choledocholithiasis. Patients: Twenty-six patients with acute cholecystitis and choledocholithiasis, but without pericholecystic liver abscess, were evaluated. After ES and extraction of stones, ETGBD was performed immediately. Results: In 24 of the 26 patients with ES, complete bile duct clearance was achieved. In the other two cases treated with ES, stones could be completely removed in an additional session after ETGBD. ETGBD was successfully performed in 23 patients (88%). In three patients with unsuccessful ETGBD, a percutaneous cholecystostomy (PC) was performed. Of the 23 patients that underwent ETGBD, a positive clinical response at 72 h was seen in 22 (96%) patients. In one patient who did not show a clinical response at 72 h, catheter drainage was continued and a positive clinical response was seen 5 days after the procedure. In three patients treated with PC, a clinical response at 72 h was seen in all cases (100%). No major procedure-related complications occurred. Conclusions: ETGBD after ES proved useful in the management of acute cholecystitis and choledocholithiasis.

A 77-year-old man was admitted for the treatment of obstructive jaundice and right hypochondralgia with high fever. An abdominal computed tomography revealed common bile duct stones and acute cholecystitis with gallstones. Magnetic resonance cholangiopancreatography revealed stones in the common bile duct. Endoscopic retrograde cholangiopancreatography also revealed stones in the common bile duct, and immediately endoscopic sphincterotomy was performed. After lithotripsy of the bile duct, continuous endoscopic nasogallbladder drainage was performed successfully. There was severe pus in the gallbladder. Next day, the patient was doing well; there was no pain and fever was down.

We describe our methods and outcomes of multidisciplinary treatments in patients with unresectable hilar cholangiocarcinoma. Fifty-seven patients with a known outcome were enrolled. Thirty-four of 57 patients were treated and evaluated by salvage therapy. For salvage therapy, we used internal and external radiotherapy, photodynamic therapy, YAG laser therapy and microwave coagulation therapy. The median survival time was 548 days for the group receiving salvage therapy and 198 days for the group not receiving this treatment. In conclusion, although no randomization of the patients was performed in this retrospective study, our present data provide convincing evidence that salvage therapy is a useful therapeutic approach for unresectable hilar cholangiocarcinomas.

Endoscopic nasobiliary drainage (ENBD) plays an important role in the treatment of patients with obstructive jaundice. Nowadays, ENBD is widely performed for not only biliary drainage, but also for gallbladder, pancreatic duct, and pancreatic cyst drainage. Herein is presented the indications for ENBD and its technique.

The procedure for endoscopic ultrasonography (EUS)-guided cystodrainage of pancreatic pseudocysts has been established but, at times, we encounter difficult cases because of infected pseudocysts. We report successful simultaneous internal and external drainage performed in three patients with severely infectious pancreatic pseudocysts.

F s h Urakami et al1 first reported a peroral direct cholangiosopy (PDCS) procedure 3 decades ago. Recently, PDCS using ltraslim upper endoscopes has been described for diagnosic and therapeutic purposes.2-9 However, those endoscopes re not dedicated cholangioscopes. This is the first report of he use of a dedicated prototype peroral direct cholangiocope to fragment a difficult bile duct stone.

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.

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. We evaluated the effectiveness of the J-tip guidewire for biliary cannulation. 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. 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. The biliary cannulation rate of the J-tip guidewire was not significantly different from those of standard guidewires.

To evaluate the safety and clinical application of high-intensity focused ultrasound (HIFU) therapy for unresectable pancreatic cancer (PC).Thirty PC patients (16 cases in stage III and 14 cases in stage IV) with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy. Informed consent was obtained. This study began at the end of 2008 and was approved by the ethics committee of our hospital [Institutional Review Board (IRB): 890]. The HIFU device used was the FEP-BY02 (Yuande Bio-Medical Engineering, Beijing, China).The mean tumor size after HIFU therapy changed to 30.9 ± 1.7 mm from 31.7 ± 1.7 mm at pre-therapy. There were no significant changes in tumor size, mean number of treatment sessions (2.7 ± 0.1 mm), or mean total treatment time (2.4 ± 0.1 h). The rate of symptom relief effect was 66.7%. The effectiveness of primary lesion treatment was as follows: complete response, 0; partial response, 4; stable disease, 22; progressive disease, 4. Treatment after HIFU therapy included 2 operations, 24 chemotherapy treatments, and 4 best supportive care treatments. Adverse events occurred in 10% of cases, namely pseudocyst formation in 2 cases and mild pancreatitis development in 1. However, no severe adverse events occurred in this study.We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

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.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.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).At mid-term outcome, ESLBD is associated with a low rate of recurrent bile duct stones, although long-term follow up is needed.

Recently, several endoscopists have described the usefulness of the endoscopic ultrasonography (EUS)-guided, single transluminal gateway technique (SGT) using transmural placement of single or multiple plastic stents or metal stents for a pancreatic pseudocyst (PC) and walled-off necrosis (WON). Moreover, the uses of the multiple transluminal gateway technique (MTGT) and single transluminal gateway transcystic multiple drainages (SGTMD) for complicated pancreatic walled-off necrosis have recently been reported. The aim of this study is to evaluate retrospectively the feasibility and efficacy of endotherapy for the treatment of complicated PC and WON cases.Eighty-nine patients with a PC (n = 14) and WON (n = 75) were treated under EUS guidance.In a total of 89 cases using SGT in combination with MTGT or SGTMD, the present study showed a technical success rate of 100 %, a final clinical success rate of 97.8 %, an adverse event during procedure rate of 0 %, an early adverse event rate of 12.4 %, and a mortality rate of 2.2 %.Even complicated WON cases can be treated using combination endotherapies, although a surgical approach as well as a percutaneous approach should be considered in the cases refractory to endoscopic therapies.

We describe a case of successful endoscopic retrograde cholangiopancreatography (ERCP) using an ultrathin endoscope for inaccessible peridiverticular papilla by a single balloon enteroscopy (SBE) in a patient with Roux-en Y (R-Y). A 73-year-old man who had total gastrectomy with R-Y for gastric cancer was admitted for acute cholangitis. Although the SBE could be advanced to the end of the afferent loop, we could not identify a major papilla, although a duodenal diverticula could be observed. The enteroscope was replaced with an ultrathin endoscope. The ultrathin endoscope allowed the papilla to be detected distal to the side of the diverticula. After pre-cutting, the ultraslim endoscope was replaced with a conventional forward-viewing endoscope. Eventually, the stones were completely removed using a balloon catheter and basket without procedure-related complication.

Pancreatic duct stones are a common complication of chronic pancreatitis. We describe successful endoscopic removal of a large pancreatic duct stone using large-balloon dilation in combination with pancreatic sphincterotomy. A 63-year-old woman was admitted for endoscopic treatment of acute on chronic pancreatitis with diabetes and epigastric pain with liver dysfunction due to a large impacted stone within the distal main pancreatic duct. Endoscopic pancreatic sphincterotomy was carried out using a wire-guided pull-type sphincterotome. Although we could carry out a relatively large incision, the stone could not be extracted. We therefore carried out papillary dilation using a large balloon (diameter 12 to 15 mm) to make room alongside the stone. A 10 × 20-mm white pancreatic duct stone was extracted during the process of pulling a dilating balloon into the working channel of the endoscope. Eventually, the second stone was removed without any procedure-related complication.