Response letter to “Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the outcomes?” with imaging aspects

Radiological imaging findings may contribute to the differentiation of malignant biliary obstruction from choledocholithiasis in the etiology of acute cholangitis.

Imaging features of malignant vs stone-induced biliary obstruction:Aspects to consider

Radiological studies play a crucial role in the evaluation of patients with biliary duct obstruction,allowing for the guidance of clinical diagnosis towards a malignant or stone-induced etiology through the recognition of relevant imaging features,which must be continuously revisited given their prognostic significance.This article aims to emphasize the importance of recognizing crucial imaging aspects of malignant and stone-induced biliary obstruction.

Still elusive: Developments in the accurate diagnosis of indeterminate biliary strictures

Indeterminate biliary strictures pose a significant diagnostic dilemma for gastroenterologists.Despite advances in endoscopic techniques and instruments,it is difficult to differentiate between benign and malignant pathology.A positive histological diagnosis is always preferred prior to high risk hepatobiliary surgery,or to inform other types of therapy.Endoscopic retrograde cholangiopancreato-graphy with brushings has low sensitivity and despite significant improvements in instruments there is still an unacceptably high false negative rate.Other methods such as endoscopic ultrasound and cholangioscopy have improved diagnostic quality.In this review we explore the techniques available to aid accurate diagnosis of indeterminate biliary strictures and obtain accurate hist-ology to facilitate clinical management.

Acute cholangitis: Does malignant biliary obstruction vs choledocholithiasis etiology change the clinical presentation and outcomes?

BACKGROUND Whether clinical outcomes of acute cholangitis(AC)vary by etiology is unclear.AIM To compare outcomes in AC caused by malignant biliary obstruction(MBO)and common bile duct stones(CBDS).METHODS This retrospective study included 516 patients undergoing endoscopic retrograde cholangiopancreatography(ERCP)due to AC caused by MBO(MBO group,n=56)and CBDS(CBDS group,n=460).Clinical and laboratory parameters were compared between the groups.Propensity score matching(PSM)created 55 matched pairs.Confounders used in the PSM analysis were age,sex,time to ERCP,and technical success of ERCP.The primary outcome comparison was 30-d mortality.The secondary outcome comparisons were intensive care unit(ICU)admission rate,length of hospital stay(LOHS),and 30-d readmission rate.RESULTS Compared with the CBDS group,the MBO group had significantly lower body temperature,percentage of abnormal white blood cell counts,and serum levels of aspartate aminotransferase,alanine aminotransferase,and creatinine.Body temperature,percent abnormal white blood cell count,and serum aspartate aminotransferase levels remained significantly lower in the MBO group in the PSM analysis.Platelet count,prothrombin time/international normalized ratio,and serum levels of alkaline phosphatase and total bilirubin were significantly higher in the MBO group.The MBO group had a significantly higher percentage of severe AC(33.9%vs 22.0%,P=0.045)and received ERCP later(median,92.5 h vs 47.4 h,P<0.001).However,the two differences were not found in the PSM analysis.The 30-d mortality(5.4%vs 0.7%,P=0.019),ICU admission rates(12.5%vs 4.8%,P=0.028),30-d readmission rates(23.2%vs 8.0%,P<0.001),and LOHS(median,16.5 d vs 7.0 d,P<0.001)were significantly higher or longer in the MBO group.However,only LOHS remained significant in the PSM analysis.Multivariate analysis revealed that time to ERCP and multiple organ dysfunction were independent factors associated with 30-d mortality.CONCLUSION MBO patients underwent ERCP later and thus had a worse prognosis than CBDS patients.Therefore,clinicians should remain vigilant in MBO patients with clinically suspected AC,and perform ERCP for biliary drainage as soon as possible.

Effectiveness of a new approach to minimally invasive surgery in palliative treatment of patients with distal malignant biliary obstruction

BACKGROUND Palliative endoscopic biliary drainage is the primary treatment option for the management of patients with jaundice which results from distal malignant biliary obstruction(DMBO).In this group of patients,decompression of the bile duct(BD)allows for pain reduction,symptom relief,chemotherapy administration,improved quality of life,and increased survival rate.To reduce the unfavorable effects of BD decompression,minimally invasive surgical techniques require continuous improvement.AIM To develop a technique for internal-external biliary-jejunal drainage(IEBJD)and assess its effectiveness in comparison to other minimally invasive procedures in the palliative treatment of patients with DMBO.METHODS A retrospective analysis of prospectively collected data was performed,which included 134 patients with DMBO who underwent palliative BD decompression.Biliary-jejunal drainage was developed to divert bile from the BD directly into the initial loops of the small intestine to prevent duodeno-biliary reflux.IEBJD was carried out using percutaneous transhepatic access.Percutaneous transhepatic biliary drainage(PTBD),endoscopic retrograde biliary stenting(ERBS),and internal-external transpapillary biliary drainage (IETBD) were used for the treatment of studypatients. Endpoints of the study were the clinical success of the procedure, the frequency andnature of complications, and the cumulative survival rate.RESULTSThere were no significant differences in the frequency of minor complications between the studygroups. Significant complications occurred in 5 (17.2%) patients in the IEBJD group, in 16 (64.0%)in the ERBS group, in 9 (47.4%) in the IETBD group, and in 12 (17.4%) in the PTBD group.Cholangitis was the most common severe complication. In the IEBJD group, the course ofcholangitis was characterized by a delayed onset and shorter duration as compared to other studygroups. The cumulative survival rate of patients who underwent IEBJD was 2.6 times higher incomparison to those of the PTBD and IETBD groups and 20% higher in comparison to that of theERBS group.CONCLUSIONIEBJD has advantages over other minimally invasive BD decompression techniques and can berecommended for the palliative treatment of patients with DMBO.

Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer

Background:Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer,and it is important to keep the stent patent as long as possible.However,few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer.This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy.Methods:Between January 2015 and May 2017,161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed.The relationship between chemotherapy and stent patency was assessed.Additionally,overall survival according to the treatment,risk factors for stent patency,and long-term adverse events were evaluated.Results:Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy(conventional gemcitabine-based chemotherapy and folfirinox)(P<0.001).Furthermore,the folfirinox group showed the longest median stent patency and overall survival,with 283 days and 466 days,respectively(P<0.001)despite higher adverse events rate.Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis(HR=0.26;95%CI:0.12–0.60;P=0.001).Conclusions:Compared with patients who received best supportive care only,patients who underwent chemotherapy after stent insertion had better stent patency.More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.

Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction

Background: Endoscopic biliary decompression using bilateral self-expandable metallic stent(SEMS) placed using the stent-in-stent(SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction(MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. Methods: From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. Results: The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. Conclusions: Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.

Safety and efficacy of transpapillary bridged bilateral side-by-side stenting for unresectable malignant hilar biliary obstruction

To the Editor:Biliary drainage is most frequently performed among endoscopic procedures using pancreatobiliary endoscopy.A large-diameter metallic stent can significantly extend the patency period rather than a plastic stent for extrahepatic biliary stricture.;However,the optimal drainage for the hilar biliary obstruction is still controversial.

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.

Percutaneous insertion of a novel dedicated metal stent to treat malignant hilar biliary obstruction

BACKGROUND Percutaneous bilateral biliary stenting is an established method for the management of unresectable malignant hilar biliary obstruction.AIM To evaluate the efficacy and safety of a novel uncovered biliary stent, specifically designed for hilar reconstruction.METHODS This, single-center, retrospective study included 18 patients(mean age 71 ± 11 years;61.1% male) undergoing percutaneous transhepatic Moving cell stent(MCS) placement for hilar reconstruction using the stent-in-stent technique for malignant biliary strictures, between November 2020 and July 2021. The Patients were diagnosed with cholangiocarcinoma(12/18;66.6%), gallbladder cancer(5/18;27.7%), and colorectal liver metastasis(1/18;5.5%). Primary endpoints were technical(appropriate stent placement) and clinical(relief from jaundice) success. Secondary endpoints included stent patency, overall survival, complication rates and stent-related complications.RESULTS The technical and clinical success rates were 100%(18/18 cases). According to Kaplan-Meier analysis, the estimated overall patient survival was 80.5% and 60.4% at 6 and 12 mo respectively, while stent patency was 90.9% and 68.2% at 6 mo and 12 mo respectively. The mean stent patency was 172.53 ± 56.20 d and median stent patency was 165 d(range 83-315). Laboratory tests for cholestasis significantly improved after procedure: mean total bilirubin decreased from 15.2 ± 6.0 mg/d L to 1.3 ± 0.4 mg/d L(P < 0.001);mean γGT decreased from 1389 ± 832 U/L to 114.6 ± 53.5 U/L(P < 0.001). One periprocedural complication was reported. Stent-related complications were observed in 5 patients(27.7%), including 1 occlusion(5.5%) and 1 stent migration(5.5 %).CONCLUSION Percutaneous hilar bifurcation biliary stenting with the MCS resulted in excellent clinical and technical success rates, with acceptable complication rates. Further studies are needed to confirm these initial positive results.

Angle of covered self-expandable metallic stents after placement is a risk factor for recurrent biliary obstruction

BACKGROUND Studies have shown that covered self-expandable metallic stents(CSEMS)with a low axial forces after placement can cause early recurrent biliary obstruction(RBO)due to precipitating sludge formation.AIM To ascertain whether the angle of CSEMS after placement is a risk factor for RBO in unresectable distal malignant biliary obstruction(MBO).METHODS Between January 2010 and March 2019,261 consecutive patients underwent selfexpandable metallic stent insertion by endoscopic retrograde cholangiopancreatography at our facility,and 87 patients were included in this study.We evaluated the risk factors for RBO,including the angle of CSEMS after placement as the primary outcome.We measured the obtuse angle of CSEMS after placement on an abdominal radiograph using the SYNAPSE PACS system.We also evaluated technical and functional success,adverse events,time to RBO(TRBO),non-RBO rate,survival time,cause of RBO,and reintervention procedure as secondary outcomes.RESULTS We divided the patients into two cohorts based on the presence or absence of RBO.The angle of CSEMS after placement(per 1°and per 10°)was evaluated using the multivariate Cox proportional hazard analysis,which was an independent risk factor for RBO in unresectable distal MBO[hazard ratio,0.97 and 0.71;95%confidence interval(CI):0.94-0.99 and 0.54-0.92;P=0.01 and 0.01,respectively].For early diagnosis of RBO,the cut-off value of the angle of CSEMS after placement using the receiver operating characteristic curve was 130°[sensitivity,50.0%;specificity 85.5%;area under the curve 0.70(95%CI:0.57-0.84)].TRBO in the<130°angle group was significantly shorter than that in the≥130°angle group(P<0.01).CONCLUSION This study suggests that the angle of the CSEMS after placement for unresectable distal MBO is a risk factor for RBO.These novel results provide pertinent information for future stent management.

Cholangioscopy-assisted guidewire placement in a malignant biliary stricture: A case report

BACKGROUND Cholangioscopy has been described in case reports and series to facilitate guidewire placement in difficult benign biliary strictures.Specifically,it has been infrequently used in difficult benign anastomotic liver transplant biliary strictures to visualize the stricture orifice for guidewire placement.Here we describe a case of guidewire placement through a difficult malignant biliary stricture using single operator cholangioscopy.CASE SUMMARY A 74-year-old female presented with jaundice and weight loss.Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography(ERCP)by other endoscopists demonstrated pancreatic adenocarcinoma with a dilated cystic duct(CD)and proximal common bile duct(CBD).The associated distal CBD stricture was dilated and stented with a plastic stent.However she subsequently developed cholangitis,prompting referral for a repeat ERCP.The stent was found to have migrated distally to the confluence of the dilated CD and CBD stricture.Despite using multiple hydrophilic guidewires,the stricture could not be traversed due to preferential wire passage into the dilated CD.SpyGlass DS(Boston Scientific Corp,Marlborough,MA,United States)was then used to visualize the orifices of the CD and CBD stenosis,enabling the guidewire to be placed directly through the stricture into the proximal CBD.A WallFlex covered metal stent(Boston Scientific Corp,Marlborough,MA,United States)was successfully placed,resulting in resolution of her cholangitis.CONCLUSION To our knowledge,this is one of the first cases to describe successful cholangioscopic guidewire placement for malignant biliary strictures.

Effects of Danshen Injection on the Malignant Obstructive Jaundice in the SD Rat Model

To observe the effects of Danshen on the growth of hepatocellular carcinoma in the SD rats, a model of malignant obstructive jaundice was established by inoculation of transplanted tumor into the hepatic portal with the walker-256 hepatocarcine line, which resulted in the obstruction by the infiltration and metastasis of hepatocellular carcinoma. SD rats were divided into 4 groups： the rats were treated by 0.9 % NS （n=24, control group）, inosine＋vitamin C （n=40, InV group）, Danshen （n=40, DS group） and 5-FU （n=40, 5-FU group）, respectively. The liver function, morphological changes and the expressions of PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were observed after the treatment with the 4 agents. Our results showed that the protective effect of Danshen on liver function was significantly better than that of NS and 5-FU （P〈0.01）. No significant difference in protective effect was observed between DS group and lnV group （P〉0.05）. Danshen also provided protective effect on the morphological damage of liver caused by obstructive jaundice. The rates of carcinoma-inhibition and metastasis inhibition were significantly higher than those of NS and inosine＋vitamin C （P〈0.01）. No significant difference in this regard existed between DS group and 5-FU group （P〉0.05）. The expressions of PCNA,VEGF and ICAM-1 PCNA, VEGF and ICAM-1 in carcinoma foci, peri-carcinoma tissues, adjacent lobe （left-internal lobe） and lung tissues were lower than those in control group and InV group, with the differences being significant （P〈0.01）. No significant differences were found between DS group and 5-FU group in the expression levels of PCNA and VEGF （P〉0.05） but ICAM-1 （P〈0.05）. It is concluded that Danshen injection not only has protective effects on liver injury caused by obstructive jaundice, but can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, prevent recurrence and metastasis of hepatocarcineoma.

Efficacy and complications of inoperable malignant distal biliary obstruction treatment by metallic stents:fully covered or uncovered?

Obstructive jaundice caused by malignant distal biliary obstruction is a common clinical symptom in patients with inoperable biliary–pancreatic cancer.Endoscopic retrograde cholangiopancreatography(ERCP)-guided stent implantation is an effective treatment for obstructive jaundice.Internal stent drainage is more physiologic and associated with a better quality of life than external stent drainage methods such as percutaneous transhepatic gallbladder drainage or percutaneous transhepatic cholangiodrainage.Selfexpanding metallic stents,which may be covered and uncovered,are commonly used.However,some uncertainties remain regarding the selection of metallic stents,including drainage patency time,clinical effect,stent migration,and post-operative complications such as pancreatitis,bleeding,and cholecystitis.This review aims to summarize the current progress and controversies surrounding the use of covered or uncovered metallic stents in inoperable common biliary obstruction via ERCP.

A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection

HepatoBiliary Surg Nutr 2021;10(4):464-475|http://dx.doi.org/10.21037/hbsn.2020.01.07 Original Article A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection Seogsong Jeong1,2#,Guijuan Luo2,3#,Qiang Gao4#,Jing Chen2,3#,Xiaolong Liu5,Liangqing Dong4,Yongjie Zhang6,Feng Shen7,Qingbao Cheng8,Chengjun Sui9,Jingfeng Liu5,Hongyang Wang2,3,Qiang Xia1,Lei Chen2,101Department of Liver Surgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai,China;2International Cooperation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Institute,Second Military Medical University,Shanghai,China;3National Center for Liver Cancer,Shanghai,China;4Department of Liver Surgery and Transplantation,Liver Cancer Institute,Zhongshan Hospital,and Key Laboratory of Carcinogenesis and Cancer Invasion(Ministry of Education),Fudan University,Shanghai,China;5Mengchao Hepatobiliary Hospital,Fujian Medical University,Fuzhou,China;6Biliary Tract Department II,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China;7Department of Hepatobiliary Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China;8Biliary Tract Department I,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China;9Department of Special Medical Care&Liver Transplantation,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,China;10Shanghai Cancer Center,Shanghai Medical College,Fudan University;Shanghai,China Contributions:(I)Conception and design:S Jeong,G Luo,Q Gao,J Chen,J Liu,H Wang,Q Xia,L Chen;(II)Administrative support:All authors;(III)Provision of study materials or patients:S Jeong,G Luo,Q Gao,J Chen,J Liu,H Wang,Q Xia,L Chen;(IV)Collection and assembly of data:All authors;(V)Data analysis and interpretation:S Jeong,G Luo,Q Gao,J Chen,J Liu,H Wang,Q Xia,L Chen;(VI)Manuscript writing:All authors;(VII)Final approval of manuscript:All authors.#These authors contributed equally to this work.Correspondence to:Lei Chen;Hongyang Wang.International Cooperation Laboratory on Signal Transduction,Eastern Hepatobiliary Surgery Institute,Second Military Medical University,225 Changhai Road,Shanghai 200438,China.Email:chenlei@smmu.edu.cn;hywangk@vip.sina.com;Qiang Xia.Department of Liver Surgery,Renji Hospital,School of Medicine,Shanghai Jiao Tong University,160 Pujian Road,Shanghai 200127,China.Email:xiaqiang@shsmu.edu.cn.

Evaluation of Intraductal Ultrasonography, Endoscopic Brush Cytology and K-ras, P53 Gene Mutation in the Early Diagnosis of Malignant Bile Duct Stricture

Background： In qualitative diagnosis of bile duct stenosis, single diagnostic measure is difficult to make a correct diagnosis, to combine several diagnostic techniques may be helpful to make an accurate diagnosis. The aim of this study was to evaluate the value of intraductal ultrasonography （IDUS）, endoscopic brush cytology and K-ras, P53 gene mutation in the early diagnosis of malignant biliary stricture. Methods： From February 2012 to February 2013, 84 patients with suspected malignant biliary stricture were performed I DUS firstly, then endoscopic brush cytology and finally K-ras, P53 gene mutation detection, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of all above ways were evaluated and compared. Results： Of 84 patients, 52 cases were ultimately diagnosed malignant biliary stenosis; of which, 9 cases had no recurrence or metastasis to other organs after radical operation during the follow-up period. IDUS combined with brush cytology and K-ras ＋ P53 gene mutation detection had obvious advantage in the sensitivity, accuracy and negative predictive value than any other joint detection and single detection （the advantage was more significant compared with IDUS ＋ brush cytology or any single detection P 〈 0.01）. There were obvious statistical significance in the sensitivity and accuracy between IDUS ＋ brush cytology ＋ P53 or IDUS ＋ brush cytology ＋ K-ras and IDUS ＋ brush cytology or IDUS （P 〈 0.05）. There was no statistical significance in the sensitivity, specificity, positive predictive value, negative predictive value and accuracy between IDUS ＋ brush cytology ＋ P53 and IDUS ＋ brush cytology ＋ K-ras （P 〉 0.05）. Conclusions： IDUS combined with brush cytology and K-ras, P53 gene mutation detection is better than the separate detection and contribute to the early diagnosis of malignant biliary stricture. Its more widespread use is recommended.