Pancreatic stents for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis should be inserted up to the pancreatic body or tail

AIM To investigate the location to which a pancreatic stent should be inserted to prevent post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis(PEP).METHODS Over a ten-year period at our hospital, 296 patients underwent their first ERCP procedure and had a pancreatic stent inserted; this study included 147 patients who had ERCP performed primarily for biliary investigation and had a pancreatic stent inserted to prevent PEP. We dividedthese patients into two groups: 131 patients with a stent inserted into the pancreatic head(head group) and 16 patients with a stent inserted up to the pancreatic body or tail(body/tail group). Patient characteristics and ERCP factors were compared between the groups.RESULTS Pancreatic amylase isoenzyme(p-AMY) levels in the head group were significantly higher than those in the body/tail group [138.5(7.0-2086) vs 78.5(5.0-1266.5), P = 0.03] [median(range)]. No cases of PEP were detected in the body/tail group [head group, 12(9.2%)]. Of the risk factors for post-ERCP hyperamylasemia(≥ p-AMY median, 131 IU/L), procedure time ≥ 60 min [odds ratio(OR) 2.65, 95%CI: 1.17-6.02, P = 0.02) and stent insertion into the pancreatic head(OR 3.80, 95%CI: 1.12-12.9, P = 0.03) were identified as independent risk factors by multivariate analysis.CONCLUSION Stent insertion up to the pancreatic body or tail reduces the risk of post-ERCP hyperamylasemia and may reduce the risk of PEP.

Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading

AIM: To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA) for grading pancreatic neuroendocrine tumors(PNETs).METHODS: A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital.Among these cases,we targeted 10 PNET patients who were evaluated according to the World Health Organization(WHO) 2010 classification.Surgery was performed in eight patients,and chemotherapy was performed in two patients due to multiple liver metastases.Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin,synaptophysin,CD56,and Ki-67.The specimens were graded by the Ki-67 index according to the WHO 2010 classification.Specimens obtained by surgery were graded by the Ki-67 indexand mitotic count(WHO 2010 classification).For the eight specimens obtained by EUS-FNA,the Ki-67 index results were compared with those obtained by surgery.In the two cases treated with chemotherapy,the effects and prognoses were evaluated.RESULTS: The sampling rate for histological diagnosis by EUS-FNA was 100%.No adverse effects were observed.The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5%(7/8).Fo r t h e t w o c a s e s t re a t e d w i t h c h e m o t h e ra p y,case 1 received somatostatin analog therapy and transcatheter arterial infusion(TAI) targeting multiple liver metastases.Subsequent treatment consisted of everolimus.During chemotherapy,the primary tumor remained unconfirmed,although the multiple liver metastases diminished dramatically.Case 2 was classified as neuroendocrine carcinoma(NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore,cisplatin and irinotecan therapy was started.However,severe adverse effects,including renal failure and diarrhea,were observed,and the therapy regimen was changed to cisplatin and etoposide.TAI targeting multiple liver metastases was performed.Although the liver metastases diminished,the primary tumor remained unconfirmed.These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor(NET) and NEC cases.These two subjects are still alive.CONCLUSION: EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification,enabling informed decisions on unresectable PNET treatment by identifying NET or NEC.

Predictive factors for the failure of endoscopic stent-instent self-expandable metallic stent placement to treat malignant hilar biliary obstruction

AIM To investigate the factors predictive of failure when placing a second biliary self-expandable metallic stents(SEMSs). METHODS This study evaluated 65 patients with an unresectable malignant hilar biliary obstruction who were examined in our hospital. Sixty-two of these patients were recruited to the study and divided into two groups: the success group, which consisted of patients in whom a stent-in-stent SEMS had been placed successfully, and the failure group, which consisted of patients in whom the stent-in-stent SEMS had not been placed successfully. We compared the characteristics of the patients, the stricture state of their biliary ducts, and the implemented endoscopic retrograde cholangiopancreatography(ERCP) procedures between the two groups.RESULTS The angle between the target biliary duct stricture and the first implanted SEMS was significantly larger in the failure group than in the success group. There were significantly fewer wire or dilation devices(ERCP catheter, dilator, or balloon catheter) passing the first SEMS cell in the failure group than in the success group. The cut-off value of the angle predicting stent-in-stent SEMS placement failure was 49.7 degrees according to the ROC curve(sensitivity 91.7%, specificity 61.2%). Furthermore, the angle was significantly smaller in patients with wire or dilation devices passing the first SEMS cell than in patients without wire or dilation devices passing the first SEMS cell. CONCLUSION A large angle was identified as a predictive factor for failure of stent-in-stent SEMS placement.

Endoscopic therapy for esophageal hematoma with blue rubber bleb nevus syndrome

A 57-year-old woman previously diagnosed with blue rubber bleb nevus syndrome(BRBNS) reported hematemesis. BRBNS is a rare vascular anomaly syndrome consisting of multifocal hemangiomas of the skin and gastrointestinal(GI) tract but her GI tract had never been examined. An upper gastrointestinal endoscopy revealed a large bleeding esophageal hematoma positioned between the thoracic esophagus and the gastric cardia. An endoscopic injection of polidocanol was used to stop the hematoma from bleeding. The hematoma was incised using the injectionneedle to reduce the pressure within it. Finally, argon plasma coagulation(APC) was applied to the edge of the incision. The esophageal hematoma disappeared seven days later. Two months after the endoscopic the rapy, the eso phage alulcerhealed and the hemangioma did not relapse. This rare case of a large esophageal hematoma originating from a hemangioma with BRBNS was treated using a combination of endoscopic therapy with polidocanol injection, incision, and APC.

Which scope is appropriate for endoscopic retrograde cholangiopancreatography after Billroth II reconstruction:An esophagogastroduodenoscope or a colonoscope?

BACKGROUND Recently,with the advent of more advanced devices and endoscopic techniques,endoscopic retrograde cholangiopancreatography(ERCP)in Billroth II(B-II)patients has been increasingly performed.However,the procedures are difficult,and the techniques and strategies have not been defined.AIM To reveal the appropriate scope for ERCP in B-II patients.METHODS Sixty ERCP procedures were performed on B-II patients between June 2005 and May 2018 at Fukushima Medical University Hospital,and in 44 cases,this was the first ERCP procedure performed by esophagogastroduodenoscopy(EGDS)or colonoscopy(CS)after B-II gastrectomy.These cases were divided into two groups:17 cases of ERCP performed by EGDS(EGDS group)and 27 cases of ERCP performed by CS(CS group).The patient characteristics and ERCP procedures were compared between the EGDS and CS groups.RESULTS The procedural time was significantly shorter in the EGDS group than in the CS group[median(range):60(20-100)vs 90(40-128)min,P value<0.01].CS was an independent factor of a longer ERCP procedural time according to the univariate and multivariate analyses(odds ratio:3.97,95%CI:1.05-15.0,P value=0.04).CONCLUSION Compared to CS,EGDS shortened the procedural time of ERCP in B-II patients.

Influence of night duty on endoscopic therapy for bile duct stones

AIM To examine the influence of night duty(ND) on endoscopic therapy for biliary duct stones.METHODS The subjects consisted of 133 patients who received initial endoscopic therapy for biliary duct stones performed by eight endoscopists after they had been on(ND group, n = 34 patients) or not [day duty(DD) group, n = 99 patients]. Patient characteristics(age, gender, history of abdominal surgery, transverse diameter of the largest stone, number of stones), years of experience of the endoscopists, endoscopic procedures [sphincterotomy, papillary balloon dilation(EPBD), papillary large balloon dilation(EPLBD)], and outcomes of initial endoscopy(procedure time; rate of stone removal by the first endoscopist; proceduresuccess rate by the first endoscopist: removal of stones or endoscopic retrograde biliary drainage; rate of final stone removal; final procedure success rate; complications; hospitalization after the procedure) were compared retrospectively between the two groups. History of abdominal surgery and treatment outcomes were also compared between the groups for each of the four endoscopists who performed most of the procedures in the ND group.RESULTS There were no significant differences regarding the number of treatments performed by each endoscopist or the years of experience between the ND and DD groups. The frequency of endoscopic retrograde cholangiopancreatography procedures did not differ significantly between the groups. There were also no significant differences regarding patient characteristics: age, gender, history of abdominal surgery(ND 7: Billroth II 4, R-Y 3; DD 18: double tract reconstruction 1, Billroth I 3, Billroth II 6, R-Y 7, duodenoduodenostomy for annular pancreas 1), transverse diameter of largest stone, and number of stones between the two groups. Among the treatment procedures, the endoscopic s p h i n c t e r o t o m y a n d E P B D r a t e s d i d n o t d i f f e r significantly between the groups. However, EPLBD was performed more frequently in the ND group [47.1%(16/34) v s 19.2%(19/99)]. Regarding outcomes, there were no significant differences in the rate of stone removal, procedure success rate, complications(ND: pancreatitis 1; DD: pancreatitis 6, duodenal bleeding 1, decreased blood pressure 1, hypoxia 2), or hospitalization after the procedure. However, the procedure time was significantly longer in the ND group(71.5 ± 44.7 vs 54.2 ± 28.8). Among the four endoscopists, there were no significant differences in patient history of abdominal surgery, removal of stones, or procedure success rate. However, the procedure time for one endoscopist was significantly longer in the ND group.CONCLUSION The time required for endoscopic therapy for bile duct stones might be influenced by ND.

Screening for hilar biliary invasion in ampullary cancer patients

BACKGROUND The treatment for ampullary cancer is pancreatoduodenectomy or local ampullectomy.However,effective methods for the preoperative investigation of hilar biliary invasion in ampullary cancer patients have not yet been identified.AIM To determine the necessity of and an appropriate method for investigating hilar biliary invasion of ampullary cancer.METHODS Among 43 ampullary cancer patients,34 underwent endoscopic treatment(n=9)or surgery(n=25).The use of imaging findings(thickening and enhancement of the bile duct wall on contrast-enhanced computed tomography,irregularity on endoscopic retrograde cholangiography,thickening of the entire bile duct wall on intraductal ultrasonography(IDUS),and partial thickening of the bile duct wall on IDUS)and biliary biopsy results for diagnosing hilar biliary invasion of ampullary cancer was compared.RESULTS Hilar invasion was not observed in every patient.Among the patients who did not undergo biliary stent insertion,the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results showed the highest accuracy(100%)for diagnosing hilar biliary invasion.However,each imaging method and biliary biopsy yielded some false-positive results.CONCLUSION Although some false-positive results were obtained with each method,the combination of partial thickening of the bile duct wall on IDUS and biliary biopsy results was useful for diagnosing hilar biliary invasion of ampullary cancer.However,hilar invasion of ampullary cancer is rare;therefore,the investigation of hilar biliary invasion of ampullary cancer might be unnecessary.

Present state of endoscopic ultrasonography-guided fine needle aspiration for the diagnosis of autoimmune pancreatitis type 1

Autoimmune pancreatitis(AIP)is defined as pancreatitis caused by irregular narrowing of the pancreatic duct accompanied by pancreatic swelling,fibrosis and lymphocyte infiltration,events that are related to autoimmune mechanisms.The 2010 International Consensus Diagnostic Criteria for AIP defined pancreatitis as“type 1”when increased levels of serum IgG4 were present and other organs were involved;lymphoplasmacytic sclerosing pancreatitis was the main histological characteristic.Apart from surgery,endoscopic ultrasonographyguided fine needle aspiration(EUS-FNA)is the only method for the histological diagnosis of AIP;however,this method is difficult.The use of larger-diameter FNA needles and trucut biopsy did not improve the diagnostic performance of EUS-FNA,but it has improved gradually.In this review,we look back at past efforts to improve the diagnostic performance of EUS-FNA and reveal the present state of EUS-FNA for the histological diagnosis of AIP type 1.

Can the wet suction technique change the efficacy of endoscopic ultrasound-guided fine-needle aspiration for diagnosing autoimmune pancreatitis type 1? A prospective single-arm study

BACKGROUND Other than surgery,endoscopic ultrasound-guided fine-needle aspiration(EUSFNA)is the only procedure for histologically diagnosing autoimmune pancreatitis(AIP).However,adequate specimens are difficult to obtain.Recently,more adequate specimens were reported to be obtained with EUS-FNA with a wet suction technique(WEST)than with conventional EUS-FNA.AIM To histologically diagnose AIP by EUS-FNA with a WEST.METHODS Eleven patients with possible type 1 AIP between February 2016 and August 2018 underwent EUS-FNA with a WEST(WEST group),with four punctures by 19 or 22 G needles.As a historical control,23 type 1 AIP patients who underwent no fewer than four punctures with 19 or 22 G needles were enrolled(DRY group).Patient characteristics and histological findings were compared between the two groups.RESULTS Three histopathological factors according to the International Consensus Diagnostic Criteria were significantly greater in the WEST group than the DRY group[lymphoplasmacytic infiltrate without granulocytic infiltration:9(81.8%)vs 6(26.1%),P=0.003,storiform fibrosis:5(45.5%)vs 1(4.3%),P=0.008,abundant(>10 cells/HPF)IgG4-positive cells:7(63.6%)vs 5(21.7%),P=0.026].Level 1 or level 2 histopathological findings were observed more often in the WEST group than in the DRY group[8(72.7%)vs 3(13.0%),P=0.001].CONCLUSION EUS-FNA with a WEST was more successful than standard EUS-FNA in histologically diagnosing AIP.

Pancreatic stents to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: A meta-analysis

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP)plays a major role in the investigation and treatment of pancreaticobiliary diseases.However,post-ERCP pancreatitis(PEP)is a severe adverse effect.Prior meta-analyses have shown that prophylactic PS was useful for preventing PEP.However,abstract reports and patients who underwent endoscopic ampullectomy were included in the previous analyses.In addition,two meta-analyses involved non-randomized controlled trials(RCTs).The efficacy of PS for preventing severe PEP was different in each meta-analysis.Therefore,we performed the current metaanalysis,which included only full-text articles,and added new findings.AIM To reveal the efficacy of prophylactic pancreatic stent(PS)placement for preventing PEP.METHODS We searched the MEDLINE,Cochrane Library and PubMed databases for related RCTs.Among the reports retrieved,11 studies were included in this metaanalysis.All full-text articles were published between 1993 and 2016.A total of 1475 patients were enrolled in the included studies;of these patients,734 had a PS inserted,and 741 did not have a PS inserted.PEP and severe PEP occurrence were evaluated in this meta-analysis.RESULTS PEP was observed in all studies and occurred in 39(5.3%)patients who received a PS.On the other hand,PEP occurred in 141(19%)patients who did not receive a PS.The occurrence of PEP was significantly lower in the patients who underwent PS placement than in the patients who did not receive a PS(OR=0.32;95%CI:0.23-0.45;P<0.001).In addition,the occurrence of severe PEP was evaluated.Notably,the occurrence of severe PEP was not observed in the stent group;however,the occurrence of severe PEP was observed in 8(1.3%)patients who did not have a PS inserted.Severe PEP occurred significantly less often in the stent group than in the no stent group(OR=0.24;95%CI:0.06-0.94;P=0.04).CONCLUSION In conclusion,prophylactic PS placement is useful for preventing PEP and severe PEP.

Appropriate number of biliary biopsies and endoscopic retrograde cholangiopancreatography sessions for diagnosing biliary tract cancer

BACKGROUND Biliary ductal cancer(BDC) is a lethal disease; however, diagnosing BDC is challenging. Biliary biopsies are performed to pathologically diagnose BDC, but the appropriate parameters for biliary biopsy [number of biliary biopsies, number of endoscopic retrograde cholangiopancreatography(ERCP) sessions, etc.] are unknown.AIM To clarify what constitutes an adequate method for biliary biopsy.METHODS In total, 95 patients who underwent endoscopic biliary biopsy without choledochoscopy and who were pathologically diagnosed with BDC were enrolled in this study. The patients were divided into two groups. Seventy-six patients who were diagnosed by biliary biopsy were defined as the positive group(P group), and nineteen patients who were not diagnosed by biliary biopsy were defined as the negative group(N group). The patient characteristics and ERCP-related procedures were compared between the P and N groups.RESULTS The numbers of ERCP sessions and biliary biopsies were significantly different between the two groups [ERCP sessions(one/two), P group 72/4 vs N group15/4, P value = 0.048; number of biliary biopsies, P group 2(1-6) vs N group 2(1-7), P value = 0.039]. In a multivariate analysis, fewer than 2 ERCP sessions was an independent factor influencing the positivity of the biliary biopsies.CONCLUSION This study clarified that ERCP and biliary ductal biopsy should only be performed once. If biliary cancer is not pathologically diagnosed after the first ERCP session, other methods(Endoscopic ultrasonography-guided fine needle aspiration or choledochoscopy-guided biliary ductal biopsy) should be employed.

Push vs pull method for endoscopic ultrasound-guided fine needle aspiration of pancreatic head lesions: Propensity score matching analysis

AIM To evaluate the efficacy of endoscopic ultrasoundguided fine needle aspiration(EUS-FNA) of pancreatic head cancer when pushing(push method) or pulling the echoendoscope(pull method).METHODS Overall, 566 pancreatic cancer patients had their first EUS-FNA between February 2001 and December 2017. Among them, 201 who underwent EUS-FNA for pancreatic head lesions were included in this study. EUS-FNA was performed by the push method in 85 patients, the pull method in 101 patients and both the push and pull methods in 15 patients. After propensity score matching(age, sex, tumor diameter, and FNA needle), 85 patients each were stratified into the push and pull groups. Patient characteristics and EUSFNA-related factors were compared between the two groups.RESULTS Patient characteristics were not significantly different between the two groups. The distance to lesion was significantly longer in the push group than in the pull group(13.9 ± 4.9 mm vs 7.0 ± 4.9 mm, P < 0.01). The push method was a significant factor influencing the distance to lesion(≥ median 10 mm)(P < 0.01). Additionally, tumor diameter ≥ 25 mm(OR = 1.91, 95%CI: 1.02-3.58, P = 0.043) and the push method(OR = 1.91, 95%CI: 1.03-3.55, P = 0.04) were significant factors contributing to the histological diagnosis of malignancy.CONCLUSION The pull method shortened the distance between the endoscope and the lesion and facilitated EUS-FNA of pancreatic head cancer. The push method contributed to the histological diagnosis of pancreatic head cancer using EUS-FNA specimens.

Biliary metal stents should be placed near the hilar duct in distal malignant biliary stricture patients

BACKGROUND Endoscopic biliary drainage using a self-expandable metallic stent(SEMS)has been widely performed to treat distal malignant biliary obstruction(DMBO).However,the optimal position of the stent remains unclear.AIM To determine the ideal position for SEMS placement.METHODS In total,135 DMBO patients underwent SEMS(uncovered or covered)placement over a ten-year period.A total of 127 patients with biliary obstruction between the junction of the cystic duct and Vater’s papilla were enrolled.An SEMS was placed through the upper common bile duct 2 cm from the biliary hilar duct in 83 patients(Hilar group)or near the top of the biliary obstruction in 44 patients(Lower group).Technical and functional success,adverse events,and risk factors for SEMS dysfunction were evaluated.RESULTS The stent patency period was significantly longer in the Hilar group than in the Lower group(P value<0.01).In multivariate analysis,the only statistically significant risk factor for SEMS dysfunction was being in the Lower group(hazard ratio:9.94,95%confidence interval:2.25–44.0,P<0.01).CONCLUSION A longer patency period was achieved by positioning the SEMS near the biliary hilar duct.

Pancreatic neuroendocrine tumor Grade 1 patients followed up without surgery:Case series

Among the three grades of neuroendocrine tumors(NETs),the prognosis for Grade 1(G1) with surgery is very good.Therefore,we evaluated the prognoses of pancreatic NET(PNET) G1 patients without surgery.A total of 8 patients who were diagnosed with NET G1,with an observation period of more than 6 mo until surgery or without surgery,were recruited.The patients who underwent surgery were ultimately diagnosed using specimens obtained during the surgery,whereas the patients who did not undergo surgery were diagnosed using specimens obtained by endoscopic ultrasonography-guided fine needle aspiration.Overall,we mainly evaluated the observation period and tumor growth.The observation period for the five cases with surgery ranged from 6-80 mo,and tumor growth was observed in one case.In contrast,the observation period for the three cases without surgery ranged from 17-54 mo,and tumor growth was not observed.Therefore,although the first-choice treatment for NETs is surgery,our experience includes certain NET G1 patients who were followed up without surgery.

Dysbiosis of the duodenal microbiota as a diagnostic marker for pancreaticobiliary cancer

BACKGROUND Pancreaticobiliary cancer(PB Ca)is a lethal disease,and a useful diagnostic marker is urgently needed.A correlation between the human microbiota and malignant gastrointestinal diseases was recently reported.AIM To investigate the efficacy of the duodenal microbiota for diagnosing PB Ca.METHODS We recruited 22 patients with benign pancreaticobiliary diseases(benign group)and 12 patients with PB Ca(malignant group).The duodenal microbiota of each patient was analyzed by the 16S rDNA terminal restriction fragment length polymorphism method.Patient characteristics,tumor markers,and relative abundances of the duodenal microbiota were compared between the benign and malignant groups.RESULTS Cancer antigen 19-9(CA19-9),Bifidobacterium,Clostridium cluster XVIII,and Prevotella levels differed significantly between the benign and malignant groups.Clostridium cluster XVIII had the greatest area under the receiver operating characteristic curve(AUC)among the four factors with respect to diagnosing PB Ca(cutoff value:3.038%;sensitivity:58.3%;specificity:95.2%;AUC:0.81).The combination of Clostridium cluster XVIII(cutoff value:3.038%)and CA19-9 Levels(cutoff value:18.8 U/mL)showed 91.7%sensitivity and 71.4%specificity for diagnosing PB Ca.CONCLUSION The duodenal microbiota may be useful for PB Ca screening.

Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis using pancreatic stents: A review of efficacy, diameter and length

Although endoscopic retrograde cholangiopancreatography (ERCP) is an important procedure for the diagnosis and treatment of pancreaticobiliary diseases, post-ERCP pancreatitis (PEP) is the most frequent adverse event that can sometimes be fatal. However, prophylactic pancreatic stent (PS) insertion has been performed to prevent PEP in high-risk patients. In some randomized controlled trials (RCTs) and meta-analyses, the efficacy of prophylactic PS insertion has been shown to prevent PEP. In addition, several types of stents have been used to decrease PEP. In this review, we introduce the details of these RCTs and meta-analyses and reveal the specifications for stent placement, for example, the stent diameter and length and the pancreatic region into which the stent should be inserted.