Increased post-endoscopic retrograde cholangiopancreatography pancreatitis for choledocholithiasis without acute cholangitis.

BACKGROUND AND AIM: Choledocholithiasis is the most common indication for endoscopic retrograde cholangiopancreatography (ERCP). Identifying risk factors for post-ERCP pancreatitis (PEP) is important for reducing the risk of developing PEP after common bile duct (CBD) stone removal. However, studies examining the risk factors for PEP for CBD stones are scarce. The aim of this study was to examine whether the presence or absence of acute cholangitis is a clinical risk factor for PEP in patients with CBD stones. METHODS: In this multicenter retrospective study, 1539 patients with naïve papillae were divided into patients without and with acute cholangitis. We compared the incidence of PEP between the two groups using one-to-one propensity score matching to adjust for the potential confounding factors of PEP. RESULTS: In the entire cohort, the rates of PEP in patients without and with acute cholangitis were 9.6% (52/542) and 1.8% (18/997), respectively (P < 0.001, odds ratio = 5.8). In the propensity-matched cohort, the rates of PEP in patients without and with acute cholangitis were 8.3% (27/326) and 2.5% (8/326), respectively (P = 0.002, odds ratio = 3.6). The rate of PEP was significantly higher in patients without acute cholangitis than in those with acute cholangitis after adjusting for the confounding factors of PEP. CONCLUSIONS: The absence of acute cholangitis may be an important clinical risk factor for PEP due to CBD stone removal. In patients without acute cholangitis, endoscopists should explain the specific risk of PEP carefully and actively implement prophylaxis against PEP.

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with asymptomatic common bile duct stones.

BACKGROUND AND AIM: For asymptomatic common bile duct (CBD) stones, removal by endoscopic retrograde cholangiopancreatography (ERCP) is recommended in available guidelines. However, few studies have reported the risk of post-ERCP pancreatitis (PEP), which is the most common and serious ERCP-related complication for asymptomatic CBD stones. We performed a propensity score matching analysis to examine the risk of PEP in therapeutic ERCP for asymptomatic CBD stones. METHODS: Information from medical databases of three institutions in Japan was collected over 6 years to identify 1113 patients with native papilla who underwent therapeutic ERCP for choledocholithiasis (excluding biliary pancreatitis). We compared the risk of PEP between asymptomatic and symptomatic groups by performing one-to-one propensity score matching. RESULTS: PEP was present in 52 (4.7%) of the 1113 patients overall. Of the 949 symptomatic patients, 28 (3.0%) had PEP, and of the 164 asymptomatic patients, 24 (14.6%) had PEP. The incidence of PEP was significantly higher in the asymptomatic group than in the symptomatic group (3.0% vs 14.6%; P < 0.001, odds ratio = 5.6). Of the 158 propensity score-matched symptomatic patients, five (3.2%) had PEP. In contrast, of the 158 propensity score-matched asymptomatic patients, 24 (15.2%) had PEP. Propensity score matching analysis revealed that the risk of PEP increased significantly in the asymptomatic group compared with the symptomatic group (3.2% vs 15.2%; P < 0.001, odds ratio = 5.5). CONCLUSIONS: ERCP for asymptomatic CBD stones had a high risk of PEP. Endoscopists should explain in detail the risk of PEP to patients, especially those with asymptomatic CBD stones.

[Clinical examination of cases of radiation proctitis after intensity-modulated radiation therapy for prostate cancer].

In our series of 366 patients who received intensity-modulated radiation therapy (IMRT) for prostate cancer, radiation proctitis developed in 24 patients. We examined the endoscopic evidence and clinical characteristics of radiation proctitis in these patients. The onset time was 2-29 months after treatment, with bloody bowel discharge being the most common symptom (22 cases). Colonoscopy revealed that the lesions tended to be concentrated on the rectal right anterior wall. Severity, according to the Tada classification, was 0b or Ia in 70.8% of all cases. The incidence of radiation proctitis decreased, and the clinical and endoscopic findings showed only mild radiation proctitis after IMRT.

[A case of pulmonary embolism due to heparin-induced thrombocytopenia after the placement of hepatic arterial infusion catheter].

A 68-year-old woman developed acute pulmonary embolism after hepatic arterial infusion therapy for advanced hepatocellular carcinoma. Because the platelet count was significantly reduced, heparin-induced thrombocytopenia (HIT) due to heparin usage in hepatic arterial infusion therapy was clinically suspected. Subsequently, the patient tested positively for HIT antibodies, and a definitive diagnosis was obtained. Antithrombotic therapy with heparin was discontinued and treatment with argatroban was started. After the heparinized hydrophilic catheter was removed, the platelet count improved immediately. HIT should be considered when a decrease in platelet count and thrombosis are involved with the usage of heparin.

Endoscopic retrograde cholangiopancreatography for bile duct stones in patients with a performance status score of 3 or 4.

BACKGROUND: As the aging population grows worldwide, the rates of endoscopic retrograde cholangiopancreatography (ERCP) for common bile duct stones (CBDS) in older patients with a poor performance status (PS) have been increasing. However, the data on the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4 are lacking, with only a few studies having investigated this issue among patients with poor PS. AIM: To examine the safety and efficacy of ERCP for CBDS in patients with a PS score of 3 or 4. METHODS: This study utilized a retrospective multi-centered design of three institutions in Japan for 8 years to identify a total of 1343 patients with CBDS having native papillae who underwent therapeutic ERCP. As a result, 1113 patients with a PS 0-2 and 230 patients with a PS 3-4 were included. One-to-one propensity-score matching was performed to compare the safety and efficacy of ERCP for CBDS between patients with a PS 0-2 and those with a PS 3-4. RESULTS: The overall ERCP-related complication rates in all patients and propensity score-matched patients with a PS 0-2 and 3-4 were 9.0% (100/1113) and 7.0% (16/230; P = 0.37), and 4.6% (9/196) and 6.6% (13/196; P = 0.51), respectively. In the propensity score-matched patients, complications were significantly more severe in the group with a PS 3-4 than in the group with a PS 0-2 group (P = 0.042). Risk factors for complications were indications of ERCP and absence of antibiotics in the multivariate analysis. Therapeutic success rates, including complete CBDS removal and permanent biliary stent placement, in propensity score-matched patients with a PS 0-2 and 3-4 were 97.4% (191/196) and 97.4% (191/196), respectively (P = 1.0). CONCLUSION: ERCP for CBDS can be effectively performed in patients with a PS 3 or 4. Nevertheless, the indication for ERCP in such patients should be carefully considered with prophylactic antibiotics.

Factors Predicting Difficult Biliary Cannulation during Endoscopic Retrograde Cholangiopancreatography for Common Bile Duct Stones.

BACKGROUND/AIMS: Difficult biliary cannulation is an important risk factor for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Therefore, this study aimed to identify the factors that predict difficult cannulation for common bile duct stones (CBDS) to reduce the risk for PEP. METHODS: This multicenter retrospective study included 1,406 consecutive patients with native papillae who underwent ERCP for CBDS. Factors predicting difficult cannulation for CBDS were identified using univariate and multivariate analyses. RESULTS: Univariate analysis showed that six factors significantly predicted difficult cannulation: ERCP performed by non-expert endoscopists, low-volume center, absence of acute cholangitis, normal serum bilirubin, intradiverticular papilla, and type of major duodenal papilla. Multivariate analysis identified ERCP performed by non-expert endoscopists (odds ratio [OR], 2.5; p<0.001), low-volume center (OR, 1.6; p<0.001), intradiverticular papilla (OR, 1.3; p=0.007), normal serum bilirubin (OR, 1.3; p=0.038), and absence of acute cholangitis (OR, 1.3; p=0.049) as factors significantly predicting difficult cannulation for CBDS. CONCLUSION: Initial cannulation by an experienced endoscopist, early rescue cannulation, or early takeover by an experienced endoscopist should be considered when performing ERCP for CBDS in the presence of factors predicting difficult cannulation.

Immediate or Interval Endoscopic Papillary Large-balloon Dilation after Limited Endoscopic Sphincterotomy for Bile Duct Stone Removal.

Objective Endoscopic papillary large-balloon dilation (EPLBD) with limited endoscopic sphincterotomy (EST) is widely used for removing multiple large common bile duct (CBD) stones. However, the safety and effectiveness of immediate EPLBD after limited EST and EPLBD at an interval after limited EST is unclear. Thus, this multicenter retrospective study was conducted to examine this matter. Methods Propensity score-matching was performed to adjust the baseline characteristics between the immediate and interval EPLBD groups. We compared the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) complications and the early outcomes of ERCP between the 2 matched groups, which comprised 66 patients each. Results The complete stone clearance rate in each study group was 100%. The overall incidence of post-ERCP complications in the propensity score-matched interval and immediate EPLBD groups was 3/33 (9.1%) and 1/33 (3.0%), respectively (p=0.61). The immediate EPLBD group had significantly fewer mean ERCP sessions for complete stone removal and a significantly lower rate of endoscopic mechanical lithotripsy (EML) usage than the interval EPLBD group [1.6 vs. 2.4 sessions, p<0.001; and 4/33 (12.1%) vs. 12/33 (36.4%), p=0.042, respectively]. Conclusion The incidence of post-ERCP complications in the immediate EPLBD group was not significantly different from that in the interval EPLBD group. Compared with interval EPLBD, immediate EPLBD may result in a reduced number of ERCP sessions for complete stone clearance and reduce the rate of EML usage.

Remaining issues of recommended management in current guidelines for asymptomatic common bile duct stones.

Current guidelines for treating asymptomatic common bile duct stones (CBDS) recommend stone removal, with endoscopic retrograde cholangiopancreatography (ERCP) being the first treatment choice. When deciding on ERCP treatment for asymptomatic CBDS, the risk of ERCP-related complications and outcome of natural history of asymptomatic CBDS should be compared. The incidence rate of ERCP-related complications, particularly of post-ERCP pancreatitis for asymptomatic CBDS, was reportedly higher than that of symptomatic CBDS, increasing the risk of ERCP-related complications for asymptomatic CBDS compared with that previously reported for biliopancreatic diseases. Although studies have reported short- to middle-term outcomes of natural history of asymptomatic CBDS, its long-term natural history is not well known. Till date, there are no prospective studies that determined whether ERCP has a better outcome than no treatment in patients with asymptomatic CBDS or not. No randomized controlled trial has evaluated the risk of early and late ERCP-related complications vs the risk of biliary complications in the wait-and-see approach, suggesting that a change is needed in our perspective on endoscopic treatment for asymptomatic CBDS. Further studies examining long-term complication risks of ERCP and wait-and-see groups for asymptomatic CBDS are warranted to discuss whether routine endoscopic treatment for asymptomatic CBDS is justified or not.

Endoscopic retrograde cholangiopancreatography-related complications for bile duct stones in asymptomatic and symptomatic patients.

BACKGROUND AND AIM: Current guidelines recommend the removal of common bile duct (CBD) stones by endoscopic retrograde cholangiopancreatography (ERCP) for both asymptomatic and symptomatic patients. We conducted this study because of the limited research comparing the risks of ERCP-related complications between these two groups. METHODS: This retrospective study involved 1491 patients with native major duodenal papilla diagnosed with choledocholithiasis at three institutions in Japan. The rates of ERCP-related complications, including post-ERCP pancreatitis (PEP), cholangitis, bleeding, and perforation, were compared using one-to-one propensity score matching between the asymptomatic and symptomatic patients. RESULTS: Complications were observed in 112 (7.5%) of the 1491 patients (asymptomatic group: 31/172 [18.0%] vs symptomatic group: 81/1319 [6.1%], P < 0.001). The rate of severe complications was higher in the asymptomatic group than that in the symptomatic group (asymptomatic group: 5/31 [16.1%] vs symptomatic group: 3/81 [3.7%], P = 0.036). In the propensity-matched asymptomatic and symptomatic patients, the incidences of PEP, cholangitis, bleeding, and perforation were 18/143 (12.6%) vs 4/143 (2.8%) (P = 0.003); 4/107 (3.7%) vs 6/107 (5.6%) (P = 0.75); 1/140 (0.7%) vs 3/140 (2.1%) (P = 0.62); and 2/140 (1.4%) vs 2/140 (1.4%) (P = 1.0). CONCLUSIONS: ERCP for asymptomatic patients with CBD stones is associated with a higher risk of overall and severe complications than that for symptomatic patients with CBD stones; the overall rate is influenced by the high incidence of PEP in the asymptomatic group. Endoscopists should explain the risk of ERCP-related complications for asymptomatic patients before performing the procedure.

Post-endoscopic retrograde cholangiopancreatography pancreatitis in single-stage endoscopic common bile duct stone removal.

BACKGROUND AND AIMS: Papillary treatment, such as endoscopic sphincterotomy or endoscopic papillary balloon dilation, and subsequent single-stage endoscopic stone removal are often performed for choledocholithiasis; however, the incidence of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is unclear. This study aimed to compare the overall incidence of PEP between single- and two-stage stone removal groups and the incidence of PEP between these two groups based on cannulation time. METHODS: We included 897 patients with native papilla who underwent papillary treatment and stone removal for choledocholithiasis with no inflammation or mild-to-moderate acute cholangitis at three institutions between April 2012 and March 2018 in Japan. We performed a propensity-matched analysis and regression adjustment by propensity score to adjust for potential confounding factors. RESULTS: In the propensity-matched analysis with 234 pairs, there was no significant difference in the overall incidence of PEP between single- and two-stage stone removal procedures (15/234, 6.4% vs 6/234, 2.6%, P = 0.072, respectively). Although single-stage stone removal after a cannulation time of ≤15 min was not a significant risk factor of PEP, the procedure after a cannulation time of >15 min was a significant risk factor of PEP as estimated by regression adjustment by propensity score (P = 0.014, 95% CI = 1.4-19.4, odds ratio = 5.2). CONCLUSIONS: Single-stage endoscopic stone removal after a long cannulation time of >15 min increased the incidence of PEP compared with the two-stage stone removal procedure. Thus, single-stage stone removal should be performed in patients with a cannulation time ≤ 15 min.

Safety and Efficacy of Endoscopic Removal of Common Bile Duct Stones in Elderly Patients ≥90 Years of Age.

Objective We examined the safety and efficacy of endoscopic stone removal for choledocholithiasis in elderly patients ≥90 years of age with native papilla and compared the outcomes with those in patients 75-89 years of age. Methods This multicenter retrospective study included 569 patients 75-89 years of age and 126 patients ≥90 years of age who had native papilla and underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis at 3 institutions in Japan between April 2012 and March 2018. The main outcomes assessed were the incidence of post-ERCP complications during hospitalization and outcomes of ERCP in patients ≥90 years of age. Results Biliary cannulation and subsequent endoscopic sphincterotomy, endoscopic balloon dilation, and endoscopic large balloon dilation were successful in 97.7% of patients 75-89 years of age and in 98.4% of patients ≥90 years of age. There was no significant difference in the incidence of post-ERCP complications between patients 75-89 years of age and those ≥90 years of age (7.7% vs. 9.5%, respectively; p=0.47). Although the rate of use of mechanical lithotripter was not significantly different, the rate of complete stone removal in patients ≥90 years of age was lower than that in patients 75-89 years of age (81.0% vs. 94.9%, respectively; p<0.001). In all cases with incomplete stone removal in both groups, permanent biliary stent placement was successful. Conclusion ERCP for choledocholithiasis in elderly patients ≥90 years of age is a safe and effective procedure; however, endoscopists should select appropriate strategies after considering each patient's medical condition and background.

Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis.

Adacolumn is a therapeutic mode for ulcerative colitis that achieves therapeutic efficacy through the adhesion of leukocytes to cellulose acetate beads. We used scanning electron microscopy and observed leukocyte adsorption on Adacolumn beads after granulocytapheresis/granulocyte and monocyte adsorption apheresis. We then compared results between two patients with a low and high C-reactive protein (CRP) levels to determine whether adhesion is affected by a difference in leukocyte activity depending on the level of inflammation. We found that the surface layers of the beads from both patients were covered by a clay-like layer, and spherical granulocytes were adsorbed here and there on top of it. In cross-section the adsorbed granulocytes were visible in the clay-like layer and the surface layer alike. The clay-like layer had a maximum thickness of approximately 12 µm in the low CRP patient and approximately 50 µm in the high CRP patient, so in the high CRP patient the clay-like adsorption layer was thicker. Taken together, adsorption onto beads is considered to involve an immunological mechanism. Our findings suggest that granulocytes contact and adhere to each other at the surface layer after adsorption, and that granulocyte-granulocyte adhesion is enhanced by a higher inflammatory response.

[A patient with an angiomyolipoma of the liver in whom the course of enlargement could be confirmed].

The patients was a 54-year-old woman. In the liver, a high-echo phyma was detected. The lesion increased from 5 to 23mm over 2 years and 4 months. On CT and MRI, it was difficult to differentiate the phyma from hepatocellular carcinoma. However, angiography revealed early outflow to the hepatic vein. In the late CTHA phase of angio-CT, there was no ring-like dark staining reaction (corona), as observed in hepatocellular carcinoma patients, outside the tumor. Hepatectomy was performed, suggesting angiomyolipoma. The course of enlargement could be followed-up, and we present findings that may be useful for differentiating this tumor from hepatocellular carcinoma.

The Incidence of Complications in Single-stage Endoscopic Stone Removal for Patients with Common Bile Duct Stones: A Propensity Score Analysis.

Objective Single-stage endoscopic stone removal for choledocholithiasis is an advantageous approach because it is associated with a shorter hospital stay; however, few studies have reported the incidence of complications related to this procedure in detail. The aim of this study was to examine the incidence of complications and efficacy of this procedure. Methods This retrospective study investigated the incidence of complications in 345 patients with naive papilla who underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis at three institutions between April 2014 and March 2016 by a propensity score analysis. The efficacy of single-stage endoscopic stone removal was assessed based on a hospital stay of within 7 days and the number of ERCP attempts. Results Among 114 patients who underwent single-stage endoscopic stone removal, 15 patients (13.2%) experienced complications. Among the remaining 231 patients in the two-stage endoscopic stone removal group, complications were observed in 17 patients (7.4%). The propensity score analysis, which was adjusted for confounding factors, revealed that single-stage endoscopic stone removal was not a significant risk factor for complications (p=0.52). In patients in whom >10 min was required for deep cannulation, single-stage endoscopic stone removal was not a significant risk factor for complications in the propensity score analysis (p=0.37). In the single-stage group, the proportion of patients with a hospital stay of within 7 days was significantly higher and the number of ERCP attempts was significantly lower in comparison to the two-stage group (p <0.0001 and <0.0001, respectively). Conclusion Single-stage endoscopic stone removal did not increase the incidence of complications associated with ERCP and was effective for reducing the hospital stay and the number of ERCP attempts.

Increased risk and severity of ERCP-related complications associated with asymptomatic common bile duct stones.

BACKGROUND AND STUDY AIMS: Endoscopic removal of asymptomatic common bile duct stones (CBDS) is generally recommended. Although many reports have described the risk of complications in endoscopic retrograde cholangiopancreatography (ERCP), no studies have addressed this problem in the context of asymptomatic CBDS. This study examines the risk of complications arising in ERCP for asymptomatic CBDS. PATIENTS AND METHODS: This retrospective study included 425 patients with naive papilla who underwent therapeutic ERCP for choledocholithiasis at 2 institutions in Japan for 2 years. The risk of complications was examined in patients who were divided into the asymptomatic and symptomatic CBDS groups. We used propensity score analysis to adjust for confounding effects. RESULTS: Complications were observed in 32 (7.5 %) of the 425 patients. Of the 358 patients with symptomatic CBDS, 14 patients (3.9 %) had complications. In contrast, of the 67 patients with asymptomatic CBDS, 18 patients (26.9 %) had complications. Propensity score analysis revealed that asymptomatic CBDS was a significant risk factor, with a significantly higher incidence of complications compared with symptomatic CBDS (odds ratio, 5.3). Moderate to severe complications were observed in 15 of 18 patients (83.3 %) in the asymptomatic CBDS group, with significantly more moderate to severe complications than those in the symptomatic CBDS (odds ratio, 6.7). CONCLUSIONS: Asymptomatic CBDS carried a high risk of ERCP-related complications, and these were often more severe. In asymptomatic CBDS, endoscopic treatment should be carefully performed after considering the patient's background, and detailed explanation of its possible complications should be given to patients in advance.

Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg-negative, and HCV-negative hepatocellular carcinoma patients.

PURPOSE: We studied the clinical features and the etiology of hepatitis B virus surface antigen (HBsAg)-negative and antibody to hepatitis C virus (anti-HCV) negative patients with hepatocellular carcinoma. METHODS: A total of 550 patients, hospitalized with an initial diagnosis of HCC were retrospectively studied. Eighty-one of these patients were HBsAg-positive (HB group), 404 patients were anti-HCV positive (HC group). The other 65 patients were negative for both HBsAg and for anti-HCV (NBNC group). We purified HBV-X gene from HCC or non-tumorous liver tissue of 23 NBNC patients using PCR. RESULTS: Clinical features of NBNC as compared with HB and HC patients were as follows, respectively: non-cirrhosis rate (%): 57,37,15 (P = 0.02 for HB, P < 0.00001 for HC), the proportion of patients with normal ALT concentrations (%): 59,28,10 (P = 0.0002 for HB, P < 0.00001 for HC). Forty of 59 NBNC patients (68%) had anti-HBs and/or anti-HBc (healthy controls: 29%, P < 0.00001) and two of 56 had serum HBV DNA. Twelve of 23 NBNC patients had HBV-X gene in HCC and/or non-cancerous liver tissues (52%). None of 52 had serum HCV RNA. CONCLUSIONS: The NBNC patients with HCC had a higher frequency of non-cirrhotic liver without liver injury. The presence of the HBV-X gene in HCC suggests a possible role of past HBV infection in the development of HCC. About half of NBNC HCC is associated with seronegativity for HBsAg and positivity for the HBV-X gene in liver tissue.