Combination immunohistochemistry for CK5/6, p63, GATA6, and HNF4a predicts clinical outcome in treatment-naïve pancreatic ductal adenocarcinoma.

Although sequence-based studies show that basal-like features lead to worse prognosis and chemotherapy-resistance compared to the classical subtype in advanced pancreatic ductal adenocarcinoma (PDAC), a surrogate biomarker distinguishing between these subtypes in routine diagnostic practice remains to be identified. We aimed to evaluate the utility of immunohistochemistry (IHC) expression subtypes generated by unsupervised hierarchical clustering based on staining scores of four markers (CK5/6, p63, GATA6, HNF4a) applied to endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) materials. EUS-FNAB materials taken from 190 treatment-naïve advanced PDAC patients were analyzed, and three IHC patterns were established (Classical, Transitional, and Basal-like pattern). Basal-like pattern (high co-expression of CK5/6 and p63 with low expression of GATA6 and HNF4a) was significantly associated with squamous differentiation histology (p < 0.001) and demonstrated the worst overall survival among our cohort (p = 0.004). IHC expression subtype (Transitional, Basal vs Classical) was an independent poor prognosticator in multivariate analysis [HR 1.58 (95% CI 1.01-2.38), p = 0.047]. Furthermore, CK5/6 expression was an independent poor prognostic factor in histological glandular type PDAC [HR 2.82 (95% CI 1.31-6.08), p = 0.008]. Our results suggest that IHC expression patterns successfully predict molecular features indicative of the Basal-like subgroup in advanced PDAC. These results provide the basis for appropriate stratification for therapeutic selection and prognostic estimation of advanced PDAC in a simplified manner.

A Prospective Study of Neoadjuvant Gemcitabine Plus Nab-paclitaxel in Patients with Borderline-resectable Pancreatic Cancer.

Objectives Neoadjuvant therapy followed by radical resection improves the borderline-resectable pancreatic cancer (BRPC) prognosis; however, the optimal therapeutic regimen remains unclear. Gemcitabine plus nab-paclitaxel (GnP) showed a high anti-tumor effect in primary lesions in a prospective study for metastatic disease. However, evidence concerning its feasibility is still lacking in patients with BRPC. We therefore evaluated the tolerability of neoadjuvant GnP (NAC-GnP) for BRPC. Methods This single-center prospective study evaluated 10 patients with BRPC who were treated with two cycles of NAC-GnP. The primary endpoint was feasibility for NAC-GnP. Treatment feasibility was defined as a successful outcome in at least eight patients. Results Ten patients who had BRPC in contact with the celiac artery (n=5), superior mesenteric artery (n=3), or hepatic artery (n=2) were enrolled. The median age was 75 (range, 40-82) years old. Grade 3 anorexia and grade 2 pneumonia occurred in one patient each, so treatment was feasible in eight patients. The median primary tumor reduction and response rates were 33% (range, 0-68%) and 60%, respectively. Six of eight patients who had abnormal CA19-9 levels at the time of enrolment showed a decrease in CA19-9 levels, with a median decrease of 72%. Five patients underwent radical resection, including R0 resection in four. Postoperative grade IIIa Clavien-Dindo complications occurred in one patient (upper gastrointestinal bleeding and pancreatic fistula). Conclusion Two-cycle NAC-GnP is a feasible treatment for patients with BRPC. Further studies on NAC-GnP in patients with BRPC are warranted.

Successful treatment of mediastinal pancreatic pseudocyst and pancreatic pleural effusion with endoscopic pancreatic duct drainage: A case report.

An 81-year-old man with chronic pancreatitis was being treated with a protease inhibitor. He developed an acute exacerbation of chronic pancreatitis and dyspnea. Contrast-enhanced computed tomography showed disruption of the main pancreatic duct, a cystic lesion connecting the mediastinum to the main pancreatic duct, and left pleural effusion. We diagnosed a pancreatic pseudocyst, mediastinal pancreatic pseudocyst, and pancreatic pleural effusion. Endoscopic retrograde pancreatography showed leakage of contrast medium from the pancreatic body; furthermore, a cystic cavity extending to the mediastinum through a pancreatic duct fistula was visualized. An endoscopic transpapillary nasopancreatic drainage tube was placed in the cystic cavity. Computed tomography showed that the mediastinal pseudocyst and pleural effusion had disappeared. Endoscopic transpapillary pancreatic duct drainage may be useful when a connection between the main pancreatic duct and a mediastinal pseudocyst is confirmed by imaging.

Efficacy and Safety of Peroral Pancreatoscopy Through the Fistula Created by Endoscopic Ultrasound-Guided Pancreaticogastrostomy.

OBJECTIVES: Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy (EUS-PGS) is a useful alternative when endoscopic retrograde pancreatography is difficult. Recently, many procedures, including peroral pancreatoscopy (POPS), have been performed through the mature fistula (MF) created by EUS-PGS. We evaluate the efficacy and safety of POPS to diagnose and treat pancreatic ductal stricture/pancreato-jejunal anastomotic stricture (PDS/PJAS) through the MF. METHODS: Twenty patients underwent EUS-PGS; 13 of these underwent POPS through the MF at Juntendo University Hospital. All patients were studied retrospectively in terms of technical and clinical success rates and adverse events (AEs). RESULTS: The technical and clinical success rates of EUS-PGS were 95% and 100%. The early and late AEs rates were 20% and 15%. The technical success rate of POPS was 100%, with one AE. Biopsy of PDS/PJAS under POPS guidance revealed recurrent/residual intrapapillary mucinous adenoma (3 patients) and benign fibrotic stricture (10 patients). In the latter patients, multiple plastic stents were placed to dilate PDS/PJAS. Four patients with improvement of PDS/PJAS were stent free, but the remaining patients were not yet. CONCLUSIONS: Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy and various procedures (including POPS) performed through the MF are feasible and effective and can diagnose and treat PDS/PJAS with acceptable AEs rates.

Endoscopic Ultrasound-guided Hepaticogastrostomy in a Seven-year-old Girl.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an effective biliary drainage procedure in adult cases with difficult biliary access. However, there have been no reports on this procedure being used in pediatric cases. We successfully performed EUS-HGS in a pediatric case with a surgically altered anatomy. A standard convex-type echoendoscope and standard devices were used, and there were no device-related complications. The benefit of EUS-HGS for pediatric patients was avoidance of a percutaneous tube, which is difficult to maintain in active children. The accumulation of further cases and performance of a prospective study are warranted to standardize and expand the experience with this procedure.

Impact of the Coronavirus Disease-2019 Pandemic on Pancreaticobiliary Disease Detection and Treatment.

The emergency declaration (ED) associated with the coronavirus disease-2019 (COVID-19) pandemic in Japan had a major effect on the management of gastrointestinal endoscopy. We retrospectively compared the number of pancreaticobiliary endoscopies and newly diagnosed pancreaticobiliary cancers before (1 April 2018 to 6 April 2020), during (7 April to 25 May 2020), and after the ED (26 May to 31 July). Multiple comparisons of the three groups were performed with respect to the presence or absence of symptoms and clinical disease stage. There were no significant differences among the three groups (Before/During/After the ED) in the mean number of diagnoses of pancreatic cancer and biliary cancer per month in each period (8.0/7.5/7.5 cases, p = 0.5, and 4.0/3.5/3.0 cases, p = 0.9, respectively). There were no significant differences among the three groups in the number of pancreaticobiliary endoscopies (EUS: endoscopic ultrasonography/ERCP: endoscopic retrograde cholangiopancreatography) per month (67.8/62.5/69.0 cases, p = 0.7 and 89.8/51.5/86.0 cases, p = 0.06, respectively), whereas the number of EUS cases decreased by 42.7% between before and during the ED. There were no significant differences among the three groups in the presence or absence of symptoms at diagnosis or clinical disease stage. There was no significant reduction in the newly diagnosed pancreaticobiliary cancer, even during the ED. The number of ERCP cases was not significantly reduced as a result of urgent procedures, but the number of EUS cases was significantly reduced.

Usefulness of Routine Plain CT the Day After an Interventional EUS Procedure.

BACKGROUND: Interventional endoscopic ultrasound-guided procedures (I-EUS) are widely accepted as salvage procedures in ERCP-failed cases, and to drain fluid collected in the abdominal cavity. Although I-EUS has a relatively high incidence of complications and is severe/fatal in some cases, no follow-up strategy has been established. In our institution, plain computed tomography (P-CT) is performed routinely the day after I-EUS. In this study, we evaluated the usefulness of routine P-CT the day after I-EUS, as a follow-up method, and propose an algorithm. METHODS: We retrospectively reviewed 81 patients who underwent I-EUS and evaluated the usefulness of P-CT, abdominal X-ray, laboratory data, and symptoms as a follow-up method. An adverse event (AE) was defined as an event requiring any treatment. RESULTS: Technical success, clinical success, and AE rates were 96.3%, 90.1%, and 18.9%, respectively. In total, 30 patients had abnormal findings among the follow-up methods: 6 cases underwent additional procedures, 8 underwent medical treatments, and 16 were observed. The sensitivity, specificity, and accuracy for detecting AEs were assessed based on P-CT (85.7%, 100%, and 97.5%), X-ray (7.1%, 100%, and 83.5%), laboratory data (71.4%, 83.0%, and 81.0%), and symptoms (92.9%, 86.2%, and 87.3%). The sensitivity and accuracy of the latter two items were as high as those for X-ray, but specificity was lower than those for X-ray and P-CT. CONCLUSIONS: Routine P-CT the day after I-EUS was useful for detecting complications and deciding to perform an invasive salvage procedure. Symptoms and laboratory data were useful to supplement routine P-CT.

IL-13Rα2 Is a Biomarker of Diagnosis and Therapeutic Response in Human Pancreatic Cancer.

IL-13Rα2 is a high-affinity binding protein for its ligand IL-13 and a cancer-testis antigen as it is expressed in the testis. IL-13Rα2 is highly expressed in various cancers, including pancreatic cancer, and consists of three domains: extracellular, transmembrane, and cytoplasmic. The extracellular domain binds to the ligand to form a biologically active complex, which initiates signaling through AP-1 and other pathways. IL-13Rα2 is also expressed in diseased cells such as fibroblasts that are involved in various inflammatory diseases, including cancer. We have reported that IL-13Rα2 is a prognostic biomarker for malignant glioma, adrenocortical cancer, and pancreatic cancer. In pancreatic cancer, a small sample of tissue could be examined for the expression of IL-13Rα2 by using the endoscopic ultrasound-fine needle aspiration technique (EUS-FNA). In addition, a peptide-based targeted approach using Pep-1L peptide could be used to study the biodistribution and whole-body cancer imaging for the screening of pancreatic cancer in suspected subjects.

Risk Factors for Stent Migration into the Abdominal Cavity after Endoscopic Ultrasound-Guided Hepaticogastrostomy.

Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is becoming increasingly popular. However, the risk factors for stent migration into the abdominal cavity remain unknown. Methods: Forty-eight patients undergoing EUS-HGS with placement of a long, partially covered self-expandable metallic stent (LPC-SEMS) were studied retrospectively to identify risk factors of stent migration. We determined the technical and functional success rates, and recorded adverse events, including stent migration. Results: EUS-HGS was technically successful in all patients. However, stent migration was evident in five patients (one actual and four imminent, 10%). Stent migration into the abdominal cavity was observed in one patient (2%), and the other four cases required additional procedures to prevent migration (8%). Logistic regression analysis revealed that the risk of stent migration increased as the initial (pre-procedure) distance between the stomach and liver at the puncture site increased (p = 0.012). Conclusions: A longer distance between the stomach and liver at the puncture site increased the risk of stent migration. However, during EUS-HGS, it is difficult to adjust the puncture position. It is important to ensure that the proportion of the stent in the stomach is large; the use of a self-anchoring stent may be optimal.

Evaluation of the Feasibility and Effectiveness of Placement of Fully Covered Self-Expandable Metallic Stents via Various Insertion Routes for Benign Biliary Strictures.

BACKGROUND AND AIMS: The goals of the management of benign biliary stricture (BBS) are to relieve symptoms and resolve short-/long-term stricture. We performed fully covered self-expandable metallic stent (hereafter, FCSEMS) placement for BBS using various methods and investigated the treatment outcomes and adverse events (AEs). METHODS: We retrospectively studied patients who underwent FCSEMS placement for refractory BBS through various approaches between January 2017 and February 2020. FCSEMS were placed for 6 months, and an additional FCSEMS was placed if the stricture had not improved. Technical success rate, stricture resolution rate, and AE were measured. RESULTS: A total of 26 patients with BBSs that were difficult to manage with plastic stents were included. The mean overall follow-up period was 43.3 ± 30.7 months. The cause of stricture was postoperative (46%), inflammatory (31%), and chronic pancreatitis (23%). There were four insertion methods: endoscopic with duodenoscopy, with enteroscopy, EUS-guided transmural, and percutaneous transhepatic. The technical success rate was 100%, without any AE. Stricture resolution was obtained in 19 (83%) of 23 cases, except for three cases of death due to other causes. Stent migration and cholangitis occurred in 23% and 6.3%, respectively. Stent fracture occurred in two cases in which FCSEMSs were placed for more than 6 months (7.2 and 10.3 months). CONCLUSION: FCSEMS placement for refractory BBS via various insertion routes was feasible and effective. FCSEMSs should be exchanged every 6 months until stricture resolution because of stent durability. Further prospective study for confirmation is required, particularly regarding EUS-guided FCSEMS placement.

Effectiveness of introducing a 20-gauge core biopsy needle with a core trap in EUS-FNA/B for diagnosing pancreatic cancer.

BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is a standard method for pathological diagnosis of pancreatic solid lesions. The EchoTip ProCore 20G® (PC20), a 20-gauge biopsy needle with a forward-bevel core trap, has been available in Japan since 2015. METHODS: We compared the efficacy of the PC20 with that of the EchoTip ProCore 22G® (PC22) and Acquire 22G® (AC22) in EUS-FNA/B for diagnosing pancreatic cancer. This retrospective study included 191 patients with pancreatic cancer who underwent EUS-FNA/B using the PC20, PC22, or AC22 at our facility from April 2013 to October 2019. We investigated the patients' clinical characteristics and the diagnostic accuracy and safety of each needle. RESULTS: A sufficient stroke length of puncture was secured in all patients. The maximum length under EUS was shorter with the AC22 (22.1 ± 2.2 mm) than PC20 (30.6 ± 0.7 mm, p < 0.01) and PC22 (30.3 ± 0.8 mm, p < 0.01). The histological accuracy was 96.4% with the PC20 but only 58.8% with the PC22 (adjusted p (p-adj) < 0.0001) and 75.0% with the AC22 (p-adj = 0.06). The diagnostic accuracy of the combination of histology and cytology was 96.4% with the PC20, while it was 72.1% with the PC22 (p-adj < 0.0001) and 91.7% with the AC22 (p-adj > 0.99). One patient (0.9%) in the PC20 group developed mild pancreatitis, but no adverse events occurred with the other needles. CONCLUSIONS: The PC20 showed better diagnostic capability than the PC22. The diagnostic efficacy was similar between the PC20 and AC22. The high histological accuracy of the PC20 could be advantageous for lesions in which histological assessment is critical.

Endoscopic ultrasound-guided antegrade procedures for managing bile duct stones in patients with surgically altered anatomy: Comparison with double-balloon enteroscopy-assisted endoscopic retrograde cholangiography (with video).

BACKGROUND AND STUDY AIM: Management of bile duct stones (BDSs) in patients with surgically altered anatomies (SAAs) remains challenging. An endoscopic ultrasound-guided antegrade (EUS-AG) procedure and double-balloon enteroscopy-assisted endoscopic retrograde cholangiography (DB-ERC) have been used to remove BDSs from patients with SAAs. However, few comparative data have been reported. Therefore, we compared the efficacy and safety of the techniques. METHODS: This was a single-center retrospective study. Patients with SAA who underwent the EUS-AG procedure or DB-ERC to remove intra- or extra-BDSs between November 2010 and March 2020 were included. The primary outcome was the technical success rate, defined as stent insertion or stone removal during the initial session. The secondary outcomes were the procedure time, incidence of adverse events (AEs), and complete stone removal rate. RESULTS: Of the 54 patients enrolled, 23 underwent the EUS-AG procedure and 31 DB-ERC. The technical success rates of EUS-AG and DB-ERC were 87.0% and 64.5%, respectively (P = 0.11). The procedure time was significantly shorter in the EUS-AG group than in the DB-ERC group (51.9 ± 15.4 vs 72.6 ± 32.2 min; P = 0.01), and the early AE rates were 26.1% and 12.9%, respectively (P = 0.71). The complete stone removal rates in patients who underwent previous stone removal were 94.1% in the EUS-AG group and 85.7% in the DB-ERC group (P = 0.61). CONCLUSION: The EUS-AG afforded technical success and complete stone removal rates comparable with those of DB-ERC, but the former procedure was shorter. The AE rate was acceptable.

Best Procedure for the Management of Common Bile Duct Stones via the Papilla: Literature Review and Analysis of Procedural Efficacy and Safety.

BACKGROUND: Endoscopic management of common bile duct stones (CBDS) is standard; however, various techniques are performed via the papilla, and the best procedure in terms of both efficacy and safety has not been determined. METHODS: Endoscopic procedures were classified into five categories according to endoscopic sphincterotomy (EST) and balloon dilation (BD): (1) EST, (2) endoscopic papillary BD (≤10 mm) (EPBD), (3) EST followed by BD (≤10 mm) (ESBD), (4) endoscopic papillary large BD (≥12 mm) (EPLBD), and (5) EST followed by large BD (≥12 mm) (ESLBD). We performed a literature review of prospective and retrospective studies to compare efficacy and adverse events (AEs). Each procedure was associated with different efficacy and AE profiles. RESULTS: In total, 19 prospective and seven retrospective studies with a total of 3930 patients were included in this study. For EST, the complete stone removal rate at the first session, rate of mechanical lithotripsy (ML), and rate of overall AEs in EST were superior to EPBD, but a higher rate of bleeding was found for EST. Based on one retrospective study, complete stone removal rate at the first session, rate of ML, and rate of overall AEs were superior for ESBD vs. EST, and the rate of bleeding for the former was also lower. Complete stone removal rate at the first session and rate of ML for ESLBD were superior to those for EST, with no significant difference in rate of AEs. For EST vs. EPLBD, complete stone removal rate at the first session and rate of ML were superior for the latter. For EPLBD vs. ESLBD, the efficacy and safety were similar. CONCLUSIONS: ESBD is considered the best procedure for the management of small CBDS, but strong evidence is lacking. For large CBDS, both ESLBD and EPLBD are similar.

Endoscopic Ultrasonography Findings of Early and Suspected Early Chronic Pancreatitis.

Chronic pancreatitis (CP) is associated with a risk of pancreatic cancer and is characterized by irreversible morphological changes, fibrosis, calcification, and exocrine and endocrine insufficiency. CP is a progressive disease with a poor prognosis and is typically diagnosed at an advanced stage. The Japan Pancreas Society proposed criteria for early CP in 2009, and their usefulness has been reported. Recently, a mechanism definition was proposed by the International Consensus Guidelines and early CP was defined as a disease state that is not based on disease duration. CP is diagnosed by computed tomography, magnetic resonance imaging, and endoscopic cholangiopancreatography, which can detect calcification and dilation of the pancreatic ducts; however, detecting early CP with these modalities is difficult because subtle changes in early CP occur before established CP or end-stage CP. Endoscopic ultrasonography (EUS) is useful in the diagnosis of early CP because it allows high-resolution, close-up observation of the pancreas. In addition to imaging findings, EUS with elastography enables measurement of the stiffness of the pancreas, an objective diagnostic measure. Understanding the EUS findings of early CP is important because a histological diagnosis is problematic, and other modalities are not capable of detecting subtle changes in early CP.

Clinical Evaluation of a Newly Developed Guidewire for Pancreatobiliary Endoscopy.

BACKGROUND: The guidewire (GW) plays an important role in pancreatobiliary endoscopy. GW quality is a critical factor in the effectiveness and efficiency of pancreatobiliary endoscopy. In this study, we evaluate a new 0.025 inch multipurpose endoscopic GW: the M-Through. METHODS: Our study was a multicenter retrospective analysis. We enrolled patients who underwent endoscopic procedures using the M-Through between May 2018 and April 2020. Patients receiving the following endoscopic treatments were enrolled: common bile duct (CBD) stone extraction, endoscopic drainage for distal and hilar malignant biliary obstruction (MBO), and endoscopic drainage for acute cholecystitis. For each procedure, we examined the rate of success without GW exchange. RESULTS: A total of 170 patients (80 with CBD stones, 60 with MBO, and 30 with cholecystitis) were enrolled. The rate of completion without GW exchange was 100% for CBD stone extraction, 83.3% for endoscopic drainage for MBO, and 43.3% for endoscopic drainage for cholecystitis. In unsuccessful cholecystitis cases with the original GW manipulator, 1 of 8 cases succeeded in the manipulator exchange. Including 6 cases who changed GW after the manipulator exchange, 11 of 16 cases succeeded in changing GW. There was significant difference in the success rate between the manipulator exchange and GW exchange (p = 0.03). The insertion of devices and stent placement after biliary cannulation (regardless of type) were almost completed with M-through. We observed no intraoperative GW-related adverse events such as perforation and bleeding due to manipulation. CONCLUSION: The 0.025 inch M-Through can be used for endoscopic retrograde cholangiopancreatography-related procedures efficiently and safely. Our study found high rates of success without GW exchange in all procedures except for endoscopic drainage for cholecystitis. This GW is considered (1) excellent for supportability of device insertion to remove CBD stones; (2) good for seeking the biliary malignant stricture but sometimes need the help of a hydrophilic GW; (3) suboptimal for gallbladder drainage that require a high level of seeking ability.

Evaluation of the safety and efficacy of minimal endoscopic sphincterotomy followed by papillary balloon dilation for the removal of common bile duct stones.

BACKGROUND/AIM: A sufficiently open papilla is needed to remove common bile duct stones (CBDS) but endoscopic sphincterotomy (EST) requires a high level of skill and is difficult with endoscopic papillary balloon dilation (EPBD). The main adverse event of EST is bleeding and perforation and that of EPBD is post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. To reduce these adverse events we employed minimal EST followed by papillary dilation (ESBD), and retrospectively evaluated its efficacy and safety compared with EST. PATIENTS AND METHODS: CBDS patients who underwent EST (n = 114) or ESBD (n = 321) at Juntendo University Hospital from January 2009 to December 2018 were consecutively enrolled, retrospectively. The exclusion criteria were large-balloon dilation (≥ 12 mm), large CBDS (>12 mm), and previous EST/EPBD. We compared the overall stone removal rate, incidence of adverse event, procedure time, number of ERCP procedures, and rate of mechanical lithotripsy (ML) between the two groups. RESULTS: Complete stone removal was successful in both ESBD and EST group. However, the rate of multiple ERCP sessions was significantly lower (35.1% vs. 12.8%, P < 0.001), procedure time was shorter (31.6 vs. 25.8 min, P = 0.01), and rate of ML was lower (16.7% vs. 7.8%, P = 0.01) in ESBD group. Bleeding was significantly more frequent in the EST group (9.6% vs. 1.2%, P < 0.001), particularly acute bleeding (7.9% vs. 0.9%, P < 0.001). CONCLUSIONS: ESBD is more efficient and safer in the management of CBD stones than EST. A prospective randomized study comparing ESBD with EST is needed to establish this combination technique.

Role of Peroral Cholangioscopy in the Diagnosis of Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is characterized by idiopathic biliary stricture followed by progressive cholestasis and fibrosis. When diagnosing PSC, its differentiation from other types of sclerosing cholangitis and cholangiocarcinoma is necessary. The cholangioscopic findings of PSC have not been investigated sufficiently. PSC and IgG4-related sclerosing cholangitis are difficult to distinguish by peroral cholangioscopy (POCS), but POCS is useful for excluding cholangiocarcinoma. POCS findings vary according to the condition and stage of disease. In the active phase, findings such as mucosal erythema, ulceration, fibrinous white exudate, and an irregular surface are observed and may reflect strong inflammation in the biliary epithelium. On the other hand, findings such as scarring, pseudodiverticula, and bile duct stenosis appear in the chronic phase and may reflect fibrosis and stenosis resulting from repeated inflammation. Observation of inside the bile duct by POCS might confirm the current PSC activity. Because POCS offers not only information regarding the diagnosis of PSC and PSC-associated cholangiocarcinoma but also the current statuses of biliary inflammation and stenosis, POCS could significantly contribute to the diagnosis and treatment of PSC once the characteristic findings of PSC are confirmed by future studies.

Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Prophylactic Efficacy of 3- or 5-cm Pancreatic Stents for Preventing Post-ERCP Pancreatitis: A Prospective, Randomized Trial.

BACKGROUND AND STUDY AIMS: Prophylactic pancreatic stent placement is effective for preventing postendoscopic retrograde cholangiopancreatography pancreatitis (PEP). The most effective type of stent, however, remains unclear. Therefore, we prospectively compared the prophylactic efficacy for PEP prevention between short (3 cm) and long (5 cm) pancreatic stent. PATIENTS AND METHODS: Between July 2012 and June 2014, 240 consecutive patients requiring therapeutic endoscopic retrograde cholangiopancreatography to remove a choledocholith or for bile drainage for obstructive jaundice were prospectively enrolled and randomized to undergo prophylactic insertion with unflanged, 5 Fr, 3 or 5-cm pancreatic stent. An efficacy of each stent for preventing PEP was evaluated as a primary endpoint. The period until stent dislodgement and the total adverse event rate were also evaluated as a secondary endpoint. RESULTS: Per-protocol analysis revealed that the PEP rate was significantly lower with the short stent than with the long stent (2.0% vs. 8.8%, P=0.035), although they were not significantly different in intention-to-treat analysis. The adverse event rate excluding PEP did not differ significantly between groups (3.0% vs. 0.9%, P=0.293). The median period until dislodgement of the short stent was significantly shorter than that of the long stent (2 vs. 4 d, P<0.001). CONCLUSIONS: The present study revealed a superiority of 3-cm stents compared with 5-cm stents for prophylactic pancreatic stent. On the basis of the past reports and the result of the present study, we recommend using a 5 Fr, 3-cm unflanged stent.This study was registered on the UMIN Clinical Trial Registry (UMIN000008290).