Current considerations on intraductal papillary neoplasms of the bile duct and pancreatic duct

Pancreatobiliary intraductal papillary neoplasms(IPNs)represent precursors of pancreatic cancer or bile duct cholangiocarcinoma that can be detected and treated.Despite advances in diagnostic methods,identifying these premalignant lesions is still challenging for treatment providers.Modern imaging,biomarkers and molecular tests for genomic alterations can be used for diagnosis and follow-up.Surgical intervention in combination with new chemotherapeutic agents is considered the optimal treatment for malignant cases.The balance between the risk of malignancy and any risk of resection guides management policy;therefore,treatment should be individualized based on a meticulous preoperative assessment of high-risk stigmata.IPN of the bile duct is more aggressive;thus,early diagnosis and surgery are crucial.The conservative management of low-risk pancreatic branch-duct lesions is safe and effective.

A new breakthrough:ESD using a newly developed grasping type scissor forceps for early gastrointestinal tract neoplasms

Endoscopic submucosal dissection(ESD) has allowed the achievement of histologically curative en bloc resection of gastrointestinal neoplasms regardless of size,permitting the resection of previously non-resectable tumors.The ESD technique for treatment of early gastric cancer has spread rapidly in Japan and a few other Asian countries due to its excellent eradication rate compared to endoscopic mucosal resection.Although numerous electrosurgical knives have been developed for ESD,technical difficulties and high complication rates(bleeding and perforation) have limited their use worldwide.We developed the grasping type scissor forceps(GSF) to resolve such ESD-related problems.Our animal and preliminary clinical studies showed that ESD using GSF is a safe(no intraoperative complication) and technically efficient(curative en bloc resection rate 92%) method for dissection of early gastrointestinal tumors.The use of GSF is a promising option for performing ESD on early stage GI tract tumors both safely and effectively.

KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

Comparison of 4-Weekly vs 3-Weekly Gemcitabine as Adjuvant Chemotherapy Following Curative Resection for Biliary Tract Cancer: A Prospective Randomized Controlled Trial

Background: Surgery for biliary tract cancer, including pancreatoduodenectomy and major hepatectomy, is too aggressive and does not allow postoperative gemcitabine to be administered by the usual dosage protocol. We hypothesized that the feasibility of 3-weekly protocol (days 1 and 8, every 3 weeks) of adjuvant gemcitabine therapy may be superior to the usual 4-weekly protocol (days 1, 8, and 15 every 4 weeks). Method: We compared the outcomes of 6 cycles of the 4-weekly protocol and 9 cycles of the 3-weekly protocol in a prospective randomized setting. The primary endpoint was the completion rate, and the secondary endpoints were the adverse events and the recurrence-free survival rate. Results: Totally, 27 patients were enrolled. The protocol could be completed without any omittances and/or dose modifications in two patients (14%) of the 4-weekly protocol, and three patients (23%) of the 3-weekly protocol (p = 0.8099);grade 3/4 neutropenia occurred in almost all the remaining (70%) patients. The relative dose intensity was 72% in the 4-weekly protocol and 78% in the 3-weekly protocol. There was no significant difference in the recurrence-free survival rate. Conclusion: The 3-weekly protocol did not yield superior completion, adverse events or recurrence-free survival rates as compared to the 4-week protocol. Trial Registration: UMIN-CTR, UMIN000001020.

Combining of chemotherapy with targeted therapy for advanced biliary tract cancer:A systematic review and meta-analysis

BACKGROUND Targeted therapy(TT)has resulted in controversial efficacy as first-line treatment for biliary tract cancer(BTC).More efficacy comparisons are required to clarify the overall effects of chemotherapy(CT)combined with TT and CT alone on advanced BTC.AIM To conduct a meta-analysis of the available evidence on the efficacy of CT combined with TT for advanced BTC.METHODS The PubMed,EMBASE,ClinicalTrials,Scopus and Cochrane Library databases were systematically searched for relevant studies published from inception to August 2022.Only randomized clinical trials(RCTs)including comparisons between the combination of gemcitabine-based CT with TT and CT alone as firstline treatment for advanced BTC were eligible(PROSPERO-CRD42022313001).The odds ratios(ORs)for the objective response rate(ORR)and hazard ratios(HRs)for both progression-free survival(PFS)and overall survival(OS)were calculated and analyzed.Subgroup analyses based on different targeted agents,CT regimens and tumor locations were prespecified.RESULTS Nine RCTs with a total of 1361 individuals were included and analyzed.The overall analysis showed a significant improvement in ORR in patients treated with CT+TT compared to those treated with CT alone(OR=1.43,95%CI:1.11-1.86,P=0.007)but no difference in PFS or OS.Similar trends were observed in the subgroup treated with agents targeting epidermal growth factor receptor(OR=1.67,95%CI:1.17-2.37,P=0.004)but not in the subgroups treated with agents targeting vascular endothelial growth factor receptor or mesenchymal-epithelial transition factor.Notably,patients who received a CT regimen of gemcitabine+oxaliplatin in the CT+TT arm had both a higher ORR(OR=1.75,95%CI:1.20-2.56,P=0.004)and longer PFS(HR=0.83,95%CI:0.70-0.99,P=0.03)than those in the CT-only arm.Moreover,patients with cholangiocarcinoma treated with CT+TT had significantly increased ORR and PFS(ORR,OR=2.06,95%CI:1.27-3.35,PFS,HR=0.79,95%CI:0.66-0.94).CONCLUSION CT+TT is a potential first-line treatment for advanced BTC that leads to improved tumor control and survival outcomes,and highlighting the importance of CT regimens and tumor types in the application of TT.

Efficacy and Safety of Chemotherapy with or without Targeted Therapy in Biliary Tract Cancer:A Meta-analysis of 7 Randomized Controlled Trials

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate（ORR） among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone（OR=1.87;95% CI：1.37–2.57;P=0.000）,but failed in the overall progression-free survival（PFS） [mean difference（MD）=0.63;95% CI：–0.45–1.72;P=0.26] and overall survival（OS）（MD=–0.67;95% CI：–2.54–1.20;P=0.49）.In the sub analysis,better ORR was obtained with the addition of EGFR（OR=1.75;95% CI：1.20–2.56;P=0.004） and VEGFR（OR=2.5;95% CI：1.28–4.87;P=0.007） targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS（MD=1.36;95% CI：0.29–2.43;P=0.01）.No significant differences were observed in the incidences of neutropenia（OR=1.37;95% CI：0.89–2.12）,thrombocytopenia（OR=1.40;95% CI：0.83–2.39）,anemia（OR=1.21;95% CI：0.62–2.38）,peripheral neuropathy（OR=1.52;95% CI：0.81–2.88）,increased AST/ALT（OR=1.40;95% CI：0.82–2.39） as well as fatigue（OR=1.65;95% CI：0.96–2.84） in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy（both targeting EGFR and VEGF） is found in the present meta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Molecular genetics and targeted therapeutics in biliary tractcarcinoma

The primary malignancies of the biliary tract, cholangio-carcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma(BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.

Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers

BACKGROUND Gemcitabine plus platinum is the standard of care first-line treatment for advanced biliary tract cancers(BTC).There is no established second-line therapy,and retrospective reviews report median progression-free survival(PFS)less than 3 mo on second-line therapy.5-Fluorouracil plus irinotecan(FOLFIRI)is a commonly used regimen in patients with BTC who have progressed on gemcitabine plus platinum,though there is a paucity of data regarding its efficacy in this population.AIM To assess the efficacy of FOLFIRI in patients with biliary tract cancers.METHODS We retrospectively identified patients with advanced BTC who were treated with FOLFIRI at MD Anderson,University of Michigan and Mayo Clinic in Jacksonville.Data were collected on patient demographics,BTC subtype,response per RECIST v1.1,progression and survival.RESULTS Ninety-eight patients were included of which 74(75%)had metastatic and 24(25%)had locally advanced disease at the time of treatment with FOLFIRI.The median age was 60(range,22-86)years.The number of patients with extrahepatic cholangiocarcinoma,gall bladder cancer and intrahepatic cholangiocarcinoma were 10,17 and 71,respectively.FOLFIRI was used as 1st,2nd,3rd or 4th–Nth lines in 8,50,36 and 4 patients,respectively.Median duration on FOLFIRI in the entire cohort was 2.2(range,0.5-8.4)mo.The median PFS and overall survival were 2.4(95%confidence interval(CI):1.7-3.1)and 6.6(95%CI:4.7-8.4)mo,respectively.Median PFS for patients treated with FOLFIRI in 1st,2nd,3rd or 4th–Nth lines were 3.1,2.5,2.3 and 1.5 mo,respectively.Eighteen patients received concurrent bevacizumab(n=13)or EGFR-targeted therapy(n=5)with FOLFIRI,with a median PFS of 2.7 mo(95%CI:1.7-5.1).CONCLUSION In this largest multi-institution retrospective review of 98 patients with BTC treated with FOLFIRI,efficacy appears to be modest with outcomes similar to other cytotoxic chemotherapy regimens.

Adjuvant treatment in biliary tract cancer: To treat or not to treat?

Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic man- agement. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of ad- juvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Welldesigned multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase Ⅲ trials may provide relevant information.

Empirical antibiotic treatment with piperacillin-tazobactam in Patients with microbiologically-documented biliary tract infections

AIM: To report our experience with empiric antimicrobial monotherapy (piperacillin/tazobactam, of which no data are available in such specific circumstances) in microbiologically-documented infections in patients with benign and malignant conditions of the biliary tract.METHODS: Twenty-three patients, 10 with benign and 13 with malignant conditions affecting the biliary tree and microbiologically-documented infections were recruited and the efficacy of empirical antibiotic therapy was assessed.RESULTS: The two groups featured similar demographic and clinical data. Overall, the infective episodes were most due to Gram negative agents, more than 60% of such episodes (mostly in malignant conditions) were preceded by invasive instrumental maneuvers. Empirical antibiotic therapy with a single agent (piperacillin/tazobactam) was effective in more than 80% of cases. No deaths were reported following infections. CONCLUSION: An empiric therapeutic approach with piperacillin/tazobactam is highly effective in biliary tract infections due to benign or malignant conditions.

仑伐替尼联合PD-1单抗及GEMOX方案在晚期胆道恶性肿瘤治疗中的临床观察

目的探讨靶免(仑伐替尼+信迪利单抗)联合GEMOX(吉西他滨+奥沙利铂)在胆道恶性肿瘤复发转移患者中的临床效果和安全性。方法选择2015年1月到2024年1月在我院中西医结合肿瘤科及肝胆外科接受靶免(仑伐替尼+信迪利单抗)联合GEMOX(吉西他滨+奥沙利铂)方案的复发转移的晚期胆道恶性肿瘤患者24例,主要观察终点设置为总体生存期(overall survival,OS)和无进展生存时间(progression-free survival,PFS),次要观察终点设置为客观缓解率(ORR)、疾病控制率(DCR)、安全性。借助肿瘤标记物(CEA、CA125、CA199)变化、不良反应、生活质量评分,影像学改变等各项数据综合评估靶免(仑伐替尼+信迪利单抗)联合GEMOX(吉西他滨+奥沙利铂)方案治疗晚期胆道恶性肿瘤复发转移的安全性和整体临床效果。结果部分缓解(PR)8例,稳定(SD)8例,进展(PD)8例,ORR 33.3%(8/24),DCR 66.7%(16/24),中位OS 13个月,中位PFS 8个月。治疗后CA199水平明显低于治疗前(P<0.05)。主要不良反应为皮疹(14/24,58.3%)、白细胞下降(22/24,91.6%)、贫血(20/24,83.3%),其中有1例因严重不良事件退出治疗,1例患者在治疗期间死于胆道梗阻合并感染。结论采用靶免(仑伐替尼+信迪利单抗)联合GEMOX(吉西他滨+奥沙利铂)方案治疗晚期胆道恶性肿瘤复发转移患者具有较高的安全性和有效性,可以在临床使用。

腹腔镜胰腺肿瘤剜除术后胆道并发症的危险因素分析

目的:探讨腹腔镜胰腺肿瘤剜除术后发生胆道并发症的危险因素。方法:回顾分析2017年3月至2023年6月101例接受腹腔镜胰腺肿瘤剜除术患者的临床及随访资料。其中男29例,女72例,15~77岁,平均(48.6±13.2)岁。肿瘤位于胰头部49例(48.5%)、胰颈体尾部52例(51.5%)。根据术后是否发生胆道并发症分为胆道并发症组(n=24)与无胆道并发症组(n=77)。单因素分析中定量数据采用t检验或Mann-Whitney U检验进行比较,分类数据采用χ^(2)检验进行比较,采用多因素Logistic回归分析术后发生胆道并发症的独立危险因素。结果:患者均在腹腔镜下顺利完成肿瘤剜除术,无术中输血及中转开腹,手术时间63~359 min,平均(168.0±58.7)min。术后长期随访,24例(23.8%)发生胆道并发症,其中胆囊结石21例、胆囊炎2例、胆囊结石合并胆总管结石1例;77例(76.2%)未发生胆道并发症。单因素分析结果显示,体重指数大(P=0.008)、术后第1天γ-谷氨酰转移酶高(P=0.04)、肿瘤位于胰头部(P=0.012)、肿瘤最大径长(P=0.028)、生长抑素使用总量多(P<0.001)是术后发生胆道并发症的危险因素。将上述危险因素纳入多因素Logistic回归分析,结果显示体重指数大(OR=1.262,95%CI=1.025~1.554,P=0.028)、肿瘤位于胰头部(OR=4.042,95%CI=1.242~13.155,P=0.020)、生长抑素使用总量多(OR=1.381,95%CI=1.059~1.800,P=0.017)是腹腔镜胰腺肿瘤剜除术后发生胆道并发症的独立危险因素。结论:腹腔镜胰腺肿瘤剜除术是治疗胰腺良性、低度恶性肿瘤的有效术式,对于具有上述危险因素的患者,应在出院后加强监测胆道并发症的发生情况。

超声内镜技术在胆胰疾病诊治中的应用研究进展

胆胰疾病的诊断及治疗是消化科临床工作中的重点及难点,疾病的早期发现和治疗对疾病预后至关重要。超声内镜具有良好的空间分辨率,与胆胰系统距离近,且可以通过细针穿刺获取组织,进行病理学诊断,在胆胰疾病诊断中发挥了不可替代的作用;近年来,随着内镜配套设备的升级和超声内镜细针穿刺技术的发展,超声内镜技术已经逐步成为一种安全、可靠的治疗手段,超声内镜引导下穿刺引流术、腹腔神经丛阻滞术、肿瘤内细针注射、精准放疗及人工智能辅助内窥镜超声等在临床的应用越来越广泛,对胆胰疾病的诊断及治疗具有重要意义。

New trends in diagnosis and management of gallbladder carcinoma

Gallbladder(GB)carcinoma,although relatively rare,is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis.It is closely associated with cholelithiasis and long-standing large(>3 cm)gallstones in up to 90%of cases.The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes,GB wall calcification(porcelain)or mainly mucosal microcalcifications,and GB polyps≥1 cm in size.Diagnosis is made by ultrasound,computed tomography(CT),and,more precisely,magnetic resonance imaging(MRI).Preoperative staging is of great importance in decisionmaking regarding therapeutic management.Preoperative staging is based on MRI findings,the leading technique for liver metastasis imaging,enhanced three-phase CT angiography,or magnetic resonance angiography for major vessel assessment.It is also necessary to use positron emission tomography(PET)-CT or ^(18)F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake.Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6%of cases.Multimodality treatment is needed,including surgical resection,targeted therapy by biological agents according to molecular testing gene mapping,chemotherapy,radiation therapy,and immunotherapy.It is of great importance to understand the updated guidelines and current treatment options.The extent of surgical intervention depends on the disease stage,ranging from simple cholecystectomy(T1a)to extended resections and including extended cholecystectomy(T1b),with wide lymph node resection in every case or IV-V segmentectomy(T2),hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y,and adjacent organ resection if necessary(T3).Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery,but much attention must be paid to avoiding injuries.In addition to surgery,novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy(neoadjuvant-adjuvant capecitabine,cisplatin,gemcitabine)have yielded promising results even in inoperable cases calling for palliation(T4).Thus,individualized treatment must be applied.

Combination Therapies for Advanced Biliary Tract Cancer

Biliary tract cancers(BTCs)are a group of malignant neoplasms that have recently increased in incidence and have a poor prognosis.Surgery is the only curative therapy.However,most patients are only indicated for palliative therapy because of advanced-stage disease at diagnosis and rapid progression.The current first-line treatment for advanced BTC is gemcitabine and cisplatin chemotherapy.Nonetheless,many patients develop resistance to this regimen.Over the years,few chemotherapy regimens have managed to improve the overall survival of patients.Accordingly,novel therapies such as targeted therapy have been introduced to treat this patient population.Extensive research on tumorigenesis and the genetic profiling of BTC have revealed the heterogenicity and potential target pathways,such as EGFR,VEGF,MEK/ERK,PI3K and mTOR.Moreover,mutational analysis has documented the presence of IDH1,FGFR2,HER2,PRKACA,PRKACB,BRAF,and KRAS gene aberrations.The emergence of immunotherapy in recent years has expanded the treatment landscape for this group of malignancies.Cancer vaccines,adoptive cell transfer,and immune checkpoint inhibitors have been extensively investigated in trials of BTC.Therefore,patient stratification and a combination of various therapies have become a reasonable and important clinical strategy to improve patient outcomes.This review elaborates the literature on combined treatment strategies for advanced BTC from the past few years and ongoing clinical trials to provide new inspiration for the treatment of advanced BTC.

晚期胆道恶性肿瘤的系统治疗进展

胆道恶性肿瘤(BTC)是一种恶性程度高、预后较差的实体肿瘤,早期诊断率低,发现时大多已处于进展期。系统化疗是晚期BTC的标准一线治疗,但总体疗效欠佳,仅极少数患者能实现降期切除或行肝移植而获得长期生存。随着肿瘤发生相关分子机制的阐明,靶向治疗获得快速发展。且免疫检查点抑制剂的问世也为改善远期预后带来新的希望。同时系统治疗的联合应用不断开展,由过去的单一治疗模式逐渐向多元化联合治疗策略转变。因此,基于肿瘤生物学行为的精准治疗以及系统联合治疗策略,将成为未来BTC研究的主要发展方向。

Interventional radiology in the management of malignant biliary obstruction

Malignant biliary obstruction is commonly due to pancreatic carcinoma,cholangiocarcinoma and metastatic disease which are often inoperable at presentation and carry a poor prognosis.Percutaneous biliary drainage and stenting provides a safe and effective method of palliation in such patients,thereby improving their quality of life.It may also be an adjunct to surgical management by improving hepatic and,indirectly,renal function before resection of the tumor.

Endoscopic stenting for inoperable malignant biliary obstruction: A systematic review and meta-analysis

AIM: To analyze through meta-analyses the benefits of two types of stents in the inoperable malignant biliary obstruction.METHODS: A systematic review of randomized clinical trials(RCT) was conducted, with the last update on March 2015, using EMBASE, CINAHL(EBSCO), MEDLINE, LILACS/CENTRAL(BVS), SCOPUS, CAPES(Brazil), and gray literature. Information of the selected studies was extracted in sight of six outcomes: primarily regarding dysfunction, complication and reintervention rates; and secondarily costs, survival, and patency time. The data about characteristics of trial participants, inclusion and exclusion criteria and types of stents were also extracted. The bias was mainly assessed through the JADAD scale. This meta-analysis was registered in the PROSPERO database by the number CRD42014015078. The analysis of the absolute risk of the outcomes was performed using the software Rev Man, by computing risk differences(RD) of dichotomous variables and mean differences(MD) of continuous variables. Data on RD and MD for each primary outcome were calculated using the MantelHaenszel test and inconsistency was qualified and reported in χ2 and the Higgins method(I2). Sensitivity analysis was performed when heterogeneity was higher than 50%, a subsequent assay was done and other findings were compiled. Student's t-test was used for the comparison of weighted arithmetic means regarding secondary outcomes.RESULTS: Initial searching identified 3660 studies; 3539 were excluded through title, repetition, and/or abstract, while 121 studies were fully assessed and were excluded mainly because they did not compare self-expanding metal stents(SEMS) and plastic stents(PS), leading to thirteen RCT selected, with 13 articles and 1133 subjects meta-analyzed. The mean age was 69.5 years old, that were affected mostly by bile duct(proximal) and pancreatic tumors(distal). The preferred SEMS diameter used was the 10 mm(30 Fr) and the preferred PS diameter used was 10 Fr. In the metaanalysis, SEMS had lower overall stent dysfunction compared to PS(21.6% vs 46.8%, P < 0.00001) and fewer re-interventions(21.6% vs 56.6%, P < 0.00001), with no difference in complications(13.7% vs 15.9%, P = 0.16). In the secondary analysis, the mean survival rate was higher in the SEMS group(182 d vs 150 d, P < 0.0001), with a higher patency period(250 d vs 124 d, P < 0.0001) and a lower cost per patient(4193.98 vs 4728.65 Euros, P < 0.0985).CONCLUSION: SEMS are associated with lower stent dysfunction, lower re-intervention rates, better survival, and higher patency time. Complications and costs showed no difference.

Endoscopic management of occluded metal biliary stents:Metal versus 10F plastic stents

AIM:To compare the efficacy of self-expandable metal stents(SEMSs) with 10F plastic stents(PSs) in the endoscopic management of occluded SEMSs.METHODS:We retrospectively reviewed the medical records of 56 patients who underwent SEMS insertion for palliation of unresectable malignant biliary obstruction between 2000 and 2007 and subsequent endoscopic retrograde biliary drainage(ERBD) with SEMS or PS for initial SEMS occlusion between 2000 and 2008.RESULTS:Subsequent ERBD with SEMS was performed in 29 patients and with PS in 27.The median time to stent occlusion after subsequent ERBD was 186 d in the SEMS group and 101 d in the PS group(P= 0.118).Overall median stent patency was 79 d for the SEMS group and 66 d for the PS group(P = 0.379).The mean number of additional biliary drainage procedures after subsequent ERBD in patients that died(n = 50) during the study period was 2.54 ± 4.12 for the SEMS group and 1.85 ± 1.95 for the PS group(P = 0.457).The mean total cost of additional biliary drainage procedures after the occlusion of subsequent SEMS or PS was $410.04 ± 692.60 for the SEMS group and $630.16 ± 671.63 for the PS group(P = 0.260).Tumor ingrowth as the cause of initial SEMS occlusion was the only factor associated with a shorter time to subsequent stent occlusion(101 d for patients with tumor ingrowth vs 268 d for patients without tumor ingrowth,P = 0.008).CONCLUSION:Subsequent ERBD with PSs offered similar patency and number of additional biliary drainage procedures compared to SEMSs in the management of occluded SEMS.

Emerging molecular targets and therapy for cholangiocarcinoma

Cholangiocarcinoma(CCA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in CCA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of CCA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. Challenges in CCA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for CCA patients.