Retrospective Comparative Study of Side-by-Side and Stent-in-Stent Metal Stent Placement for Hilar Malignant Biliary Obstruction.

BACKGROUND: In patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial. STUDY: Clinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS. RESULTS: A total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively. CONCLUSIONS: Other than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.

Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study.

Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line 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.

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.

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.

Transitional Changes of Anxiety, Pain and Other Symptoms in Cancer Patients Admitted to a Palliative Care Unit, Evaluated Using the Support Team Assessment Schedule - Japanese Version.

Objective: Association between physical symptoms and psychosocial difficulties of cancer patients has been reported widely. Nevertheless, the effects of pain and other symptom control on anxiety in such patients have not been investigated well. We investigated the association of improvement of pain and other symptoms with patient anxiety, and assessed factors associated with improvement of such symptoms. Methods: Data of patients with advanced cancer admitted to a palliative care unit during August 2018 - June 2022 were analyzed retrospectively. Severity of pain, other symptoms, and anxiety was assessed by the Support Team Assessment Schedule Japanese version (STAS-J) administered at admission and after 2 weeks. Patients' physical data, their Palliative Prognostic Index (PPI) at admission, and their overall survival were collected and recorded. Results: Data of 701 patients were analyzed. Improvement of pain or other symptoms after 2 weeks was not associated with the PPI total score or actual survival (P = .105 and .999). Patients with higher anxiety on admission experienced improvement of pain or other symptoms more frequently (P = .005). Worsening of anxiety was observed less in patients who experienced improvement in pain or other symptoms after 2 weeks (P = .027). Conclusion: Pain or other symptoms of patients with advanced cancer was improved irrespective of the general condition indicated with actual survival and prognosis-predictive factors. These findings suggest the importance of pain and other symptoms' improvement and its important roles in the management of patient psychosocial problems such as anxiety.

Results of the Tokyo trial of prevention of post-ERCP pancreatitis with risperidone-2: a multicenter, randomized, placebo-controlled, double-blind clinical trial.

BACKGROUND: Our previous study suggested that a combination of ulinastatin and risperidone reduced post-ERCP pancreatitis (PEP) compared with ulinastatin alone. OBJECTIVE: The aim of this study was to evaluate the efficacy of risperidone alone for prevention of PEP. DESIGN: A multicenter, randomized, placebo-controlled, double-blind clinical trial. SETTING: Two academic hospitals and 5 referral hospitals in Tokyo and Saitama, Japan. PATIENTS: Patients undergoing therapeutic or interventional-diagnostic ERCP. INTERVENTION: The patients were randomized to receive 2 mg of oral risperidone or oral placebo at 0.5 to 2 hours before ERCP. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the incidence of PEP. Secondary endpoints were the incidence of hyperenzymemia and enzyme levels (amylase, pancreatic amylase, lipase). Risk factors for PEP were evaluated. RESULTS: We initially enrolled 500 patients in the study (250 in the risperidone group and 250 in the placebo group), but 17 (11 in the risperidone and 6 in the placebo group) were excluded after randomization. PEP developed in 24 patients (10.0%) in the risperidone group and 21 patients (8.6%) in the placebo group (P = .587). Serum amylase levels at 3 hours after ERCP were lower in the risperidone group (P = .007 in a single test of hypothesis, significance removed by Bonferroni correction for multiple testing). In multivariate analysis, a small papilla of Vater, total procedure time ≥40 minutes, and stenosis of the intrahepatic duct were significantly associated with PEP. LIMITATIONS: Multiplicity of study centers and a relatively wide time range of drug administration time. CONCLUSION: Risperidone did not show a benefit in prevention of PEP in this trial. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT000004592.).

A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer.

BACKGROUND: To evaluate the treatment outcome of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer who were refractory to gemcitabine-based first-line chemotherapy were treated with gemcitabine and cisplatin combination therapy. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, repeated every 3 weeks. RESULTS: Sixty patients were included. The tumor response and disease control rates were 1.7 and 58.3%, respectively. The median overall survival and time to progression were 6.7 months (95% CI 4.9-8.1) and 3.5 months (95% CI 2.5-5.0), respectively. Grade 3/4 toxicities included leucopenia (20%), neutropenia (25%), anemia (23%), thrombocytopenia (17%), nausea (2%), anorexia (2%), and liver dysfunction (2%). CONCLUSIONS: Gemcitabine and cisplatin combination therapy showed moderate efficacy and safety as second-line treatment for advanced biliary tract cancer that is refractory to gemcitabine-based first-line chemotherapy.

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.

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.

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.

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.

Placement of multiple metal stents for malignant intrahepatic biliary obstruction via an endoscopic ultrasound-guided choledochoduodenostomy fistula.

Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) using a fully-covered self-expandable metal stent (SEMS) is increasingly used as an alternative to failed endoscopic retrograde cholangiopancreatography. An EUS-CDS fistula can provide endoscopists with a new approach route for intrahepatic bile ducts. Here, we present successful placement of multiple SEMS for intrahepatic biliary obstruction via an EUS-CDS fistula.

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.

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.

Incidence of malignancies in patients with IgG4-related disease.

OBJECTIVE: It has been discussed whether IgG4-related disease (IgG4-RD), including autoimmune pancreatitis (AIP), is associated with malignancy; however, the issue has not been clarified. METHODS: We analyzed 113 patients with IgG4-RD in whom malignancy was not diagnosed at the time of IgG4-RD onset and the follow-up period was longer than six months. A total of 95 patients had AIP. The mean follow-up period was 73 months. The incidence of the observed malignancies was compared with the expected incidence in an age- and sex-matched general Japanese population based on the Vital Statistics of Japan. RESULTS: There were 15 malignancies (lung cancer in five patients, pancreatic cancer in two patients, gastric cancer in two patients, bile duct cancer in one patient, renal cancer in one patient, breast cancer in one patient, tongue cancer in one patient, malignant melanoma in one patient and acute myeloid leukemia in one patient) in 14 patients during the follow-up period. The calculated standardized incidence rate of the total malignancies was not significant, that is, 1.04 (95% CI 0.57-1.75). CONCLUSION: The incidence of total malignancies in IgG4-RD patients is similar to that observed in the general population. At present, it is reasonable to conclude that IgG4-RD is not associated with an increased incidence of total malignancies.

High alcohol consumption increases the risk of pancreatic stone formation and pancreatic atrophy in autoimmune pancreatitis.

OBJECTIVES: This study aimed to investigate risk factors for pancreatic stones and atrophy in autoimmune pancreatitis (AIP). METHODS: Seventy-one patients with AIP observed for more than 1 year were enrolled. The frequency of pancreatic stone development and atrophy on computed tomography as well as their risk factors were examined. RESULTS: Pancreatic stones and atrophy were observed in 13 and 43 patients, respectively. Alcohol consumption of greater than 50 g/d was the only significant risk factor for pancreatic atrophy in univariate analysis. Alcohol intake of greater than 50 g/d was observed in 6 of 13 patients with stones and 10 of 58 patients without stones (46% vs 17%, P = 0.059). Alcohol intake of greater than 50 g/d was observed in 14 of 43 patients with atrophy and 2 of 28 patients without atrophy (33% vs 7.1%, P = 0.018). In multivariate analysis, alcohol consumption was a significant risk factor both for pancreatic stone formation (odds ratio [OR], 7.47; P = 0.040) and atrophy (OR 6.24; P = 0.034). Higher age at onset was another significant risk factor for pancreatic atrophy (OR 1.07 per year; P = 0.029). CONCLUSIONS: Alcohol consumption of greater than 50 g/d increases the risk of pancreatic stone development and atrophy in patients with AIP.