A Multicenter Open-Label Randomized Controlled Trial of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer.

OBJECTIVE: Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients. METHODS: Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival. RESULTS: A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070). CONCLUSIONS: In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

Conversion to endoscopic ultrasound-guided biliary drainage by temporary nasobiliary drainage placement in patients with prior biliary stenting.

BACKGROUND AND OBJECTIVES: Endoscopic ultrasound-guided biliary drainage (EUS-BD), first reported as an alternative to percutaneous transhepatic BD in failed endoscopic retrograde cholangiography, is sometimes performed as reintervention for transpapillary stent dysfunction such as in patients with new onset gastric outlet obstruction, but direct conversion to EUS-BD can potentially have a risk of leakage of infected bile. The aim of this study is to evaluate the safety and efficacy of conversion to EUS-BD using a temporary endoscopic nasobiliary drainage (ENBD) tube placement as a reintervention for prior BD. PATIENTS AND METHODS: Sixteen patients with prior BD for malignant biliary obstruction undergoing conversion to EUS-BD using a temporary ENBD tube placement were studied. Technical and clinical success rate and adverse events were evaluated. RESULTS: The major reason for conversion to EUS-BD was recurrent cholangitis due to duodenobiliary reflux (n = 13). In 14 patients with an indwelling covered metal or plastic stent, the stents were removed before temporary ENBD placement. After a median duration of 6 days, subsequent conversion to EUS-BD using a covered metal stent was performed, which was technically and clinically successful in all 16 patients (14 hepaticogastrostomy and 2 choledochoduodenostomy). Adverse events were observed in 3 patients (19%): one bleeding, one cholecystitis, and one cholangitis. No bile leak, peritonitis, or sepsis was observed. CONCLUSIONS: Conversion to EUS-BD using temporary ENBD tube placement in patients with prior BD was technically feasible and relatively safe without infectious complications related to bile leakage.

The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study.

OBJECTIVES: Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy. METHODS: This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups. RESULTS: A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P < 0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131). CONCLUSIONS: The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

Indications for endoscopic ultrasonography (EUS)-guided biliary intervention: Does EUS always come after failed endoscopic retrograde cholangiopancreatography?

BACKGROUND AND AIM: Endoscopic ultrasonography-guided biliary drainage (EUS-BD), first reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) after failed endoscopic retrograde cholangiopancreatography (ERCP), is increasingly reported as a primary procedure without failed ERCP. The present study aims to evaluate the outcomes of therapeutic biliary ERCP and to compare the safety and effectiveness of primary EUS-BD with those of ERCP, rescue EUS-BD and PTBD. METHODS: We retrospectively studied therapeutic biliary ERCP as well as subsequent rescue PTBD and EUS-BD. Additionally, indications, safety and technical success of primary EUS-BD were evaluated. RESULTS: Between August 2013 and September 2015, a total of 520 therapeutic biliary ERCP with a native papilla were analyzed. We encountered 23 cases with inaccessible papilla and 22 cases with failed cannulation, which were rescued by 21 PTBD, 16 EUS-BD and two repeat ERCP. Additionally, 40 primary EUS-BD were carried out during the same period as a result of 10 recurrent cholangitis cases after transpapillary drainage, five outside failed cannulation, four altered anatomy, two history of ERCP-related adverse events (AE), two technical difficulties in stenting under enteroscopy-assisted ERCP and 17 on study protocol. Technical success and AE rates were 95.6% and 14.5% in ERCP, 90.5% and 33.3% in rescue PTBD, 93.8% and 18.8% in rescue EUS-BD, and 95.0% and 22.5% in primary EUS-BD, respectively. CONCLUSIONS: Rescue EUS-BD was used in 3.1% among all ERCP. Given the comparable technical success and AE rates of both primary and rescue EUS-BD, primary EUS-BD without failed ERCP can be a treatment option if it provides advantages over ERCP.

Procalcitonin is a useful biomarker to predict severe acute cholangitis: a single-center prospective study.

BACKGROUND: Procalcitonin is being increasingly used to diagnose and grade acute systemic bacterial infection at an early stage of disease onset. The aim of this prospective study was to evaluate the usefulness of procalcitonin for severity grading of acute cholangitis on patient admission. METHODS: Patients with acute cholangitis were prospectively enrolled. The severity of acute cholangitis was graded on the basis of the 2013 Tokyo guidelines (Japanese Society of Hepato-Biliary-Pancreatic Surgery, 2013). We compared the ability of procalcitonin level on admission to predict moderate/severe (vs mild) or severe (vs mild/moderate) acute cholangitis with the abilities of white blood cell (WBC) count and C-reactive protein (CRP) level. RESULTS: Two hundred thirteen patients were analyzed, and the severity of acute cholangitis was graded as mild, moderate, and severe in 108, 76, and 29 patients respectively. Procalcitonin level, WBC count, and CRP level all increased significantly according to the severity. In the receiver operating characteristic analyses, the area under the curve for procalcitonin for severe acute cholangitis was 0.90 [95% confidence interval (CI) 0.85-0.96] and was significantly greater than that for WBC (0.62; 95% CI 0.48-0.76) and that for CRP (0.70; 95% CI 0.60-0.80). The optimal cutoff value for procalcitonin for prediction of severe acute cholangitis was 2.2 ng/mL (sensitivity 0.97; specificity 0.73; accuracy 0.77). The areas under the curve for procalcitonin, WBC, and CRP for moderate/severe acute cholangitis were not significantly different. CONCLUSIONS: Procalcitonin predicted severe acute cholangitis better than conventional biomarkers. Severe cases for which urgent biliary drainage is indicated might be identified on admission on the basis of the cutoff values for procalcitonin suggested in this study.

Safety and effectiveness of a long, partially covered metal stent for endoscopic ultrasound-guided hepaticogastrostomy in patients with malignant biliary obstruction.

Background and study aims: Endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) is potentially complicated by bile leak and stent migration. The aim of this study was to evaluate the safety and effectiveness of a long (≥ 10 cm), partially covered metal stent (LP-CMS) for EUS-guided hepaticogastrostomy (EUS-HGS) for malignant biliary obstruction. Both the stent length and the uncovered portion at the proximal end of the LP-CMS are designed to prevent stent migration. Patients and methods: A total of 33 patients undergoing EUS-HGS using an LP-CMS in four centers were retrospectively studied. Technical and clinical success, adverse events, and recurrent biliary obstruction were evaluated. Results: Gastric outlet obstruction (76 %) and surgically altered anatomy (15 %) were two major reasons for EUS-HGS. The technical and clinical success rates were 100 %. The median intragastric stent length was 54 mm. The adverse event rate was 9 %. No stent migration was observed. Recurrent biliary obstruction developed in 24 %, with a median cumulative time to recurrence of 8.5 months. Conclusions: EUS-HGS using an LP-CMS for unresectable malignant biliary obstruction was safe and effective.

No Survival Benefit from the Inhibition of Renin-Angiotensin System in Biliary Tract Cancer.

AIM: The renin-angiotensin system (RAS) was investigated as a target for cancer treatment. PATIENTS AND METHODS: A total of 287 patients with biliary tract cancer (BTC) receiving chemotherapy were retrospectively studied to evaluate the role of inhibition of RAS by angiotensin system inhibitors (ASIs). Progression-free survival (PFS) and overall survival (OS) were compared between 74 patients with hypertension, on ASIs (ASI group), 50 patients with hypertension not on ASIs (non-ASI with HT group) and 163 patients without hypertension (non-HT group). Interactions between the use of ASIs and various subgroups were explored. RESULTS: The median PFS was 3.6, 3.9 and 4.6 months (p=0.495) and the median OS was 11.6, 10.9 and 13.1 months (p=0.668), respectively. The use of ASIs was not associated with OS (hazard ratio 1.00, p=0.975) and no subgroups with better survival were identified. CONCLUSION: No survival benefit from ASIs was observed in BTC.

Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience.

The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions.

Outcome of Long-term Maintenance Steroid Therapy Cessation in Patients With Autoimmune Pancreatitis: A Prospective Study.

OBJECTIVE: To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis. PATIENTS AND METHODS: The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G<1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of >1600 mg/dL. RESULTS: During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038). CONCLUSIONS: ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period >3 years to prevent relapse.

Superiority of 10-mm-wide balloon over 8-mm-wide balloon in papillary dilation for bile duct stones: A matched cohort study.

BACKGROUND/AIMS: Endoscopic papillary balloon dilation (EPBD) is a possible alternative to endoscopic sphincterotomy (EST) for common bile duct (CBD) stones. To date, 10- and 8-mm EPBD have not been fully compared. PATIENTS AND METHODS: Patients who underwent EPBD for CBD stones at two Japanese tertiary care centers between May 1994 and January 2014 were identified. Matched pairs with 10- and 8-mm EPBD were generated. Short- and long-term outcomes were compared between the two groups. RESULTS: A total of 869 patients were identified (61 and 808 patients for 10- and 8-mm EPBD, respectively), and 61 well-balanced pairs were generated. The rate of complete stone removal within a single session was higher in the 10-mm EPBD group than in the 8-mm EPBD group (69% vs. 44%, P < 0.001), and use of lithotripsy was less frequent in the 10-mm EPBD group (23% vs. 56%, P < 0.001). The rates of post-ERCP pancreatitis were similar between the 10- and 8-mm EPBD groups (11% vs. 8%). Cumulative biliary complication-free rates were not statistically different between the two groups: 88% [95% confidence interval (CI): 79-97%] and 94% (95% CI: 88-100%) at 1 year and 69% (95% CI: 56-85%) and 80% (95% CI: 69-93%) at 2 years in the 10- and 8-mm EPBD groups, respectively. In the 10-mm EPBD group, ascending cholangitis was not observed, and pneumobilia was found in 5% of cases during the follow-up period. CONCLUSIONS: EPBD using a 10-mm balloon for CBD stones is safe and more effective than 8-mm EPBD. The sphincter function is highly preserved after 10-mm EPBD.

Risk factors for post-ERCP pancreatitis in wire-guided cannulation for therapeutic biliary ERCP.

BACKGROUND: Wire-guided cannulation (WGC) was reported to decrease post-ERCP pancreatitis (PEP), but risk factors for PEP in WGC are not fully elucidated. OBJECTIVE: To evaluate the incidence and risk factors of PEP in WGC. DESIGN: Single-center retrospective study. SETTING: Academic center. PATIENTS: A total of 800 consecutive patients with a native papilla. INTERVENTIONS: Biliary therapeutic ERCP by using WGC. MAIN OUTCOME MEASUREMENTS: The rate of PEP and its risk factors. RESULTS: Biliary cannulation was successful by using WGC alone in 70.5%, and the final cannulation rate was 96.1%. Unintentional guidewire insertion and contrast material injection into the pancreatic duct (PD) during cannulation occurred in 55.3% and 21.8%, respectively. The incidence of PEP was 9.5% (mild 5.6%, moderate 2.9%, severe 1.0%). Multivariate analysis revealed a common bile duct (CBD) diameter of <9 mm (odds ratio [OR] 2.03; P = .006) and unintentional guidewire insertion into the PD (OR 2.25; P = .014) as risk factors for PEP. PD opacification was not a risk factor for PEP (OR 1.15; P = .642), but the incremental increase of the PEP rate was seen in patients with CBDs <9 mm: 4.6% without any PD manipulation, 8.3% with contrast material alone, 16.9% with guidewire alone, and 22.1% with both contrast material and guidewire. LIMITATIONS: Retrospective design in a single center. CONCLUSION: Unintentional PD manipulation was not uncommon in WGC. Guidewire insertion into the PD and a small CBD were risk factors for PEP in biliary therapeutic ERCP with the use of WGC.

Total cholesterol level for assessing pancreatic insufficiency due to chronic pancreatitis.

BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.