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.

Iatrogenic bile duct injuries from biliary tract surgery

BACKGROUND:Cholecystectomy is the most commonly performed procedure in general surgery.However,bile duct injury is a rare but still one of the most common complications.These injuries sometimes present variably after primary surgery.Timely detection and appropriate management decrease the morbidity and mortality of the operation. METHODS:Five cases of iatrogenic bile duct injury(IBDI) were managed at the Department of Surgery,First Affiliated Hospital,Xi’an Jiaotong University.All the cases who underwent both open and laparoscopic cholecystectomy had persistent injury to the biliary tract and were treated accordingly. RESULTS:Recovery of the patients was uneventful.All patients were followed-up at the surgical outpatient department for six months to three years.So far the patients have shown good recovery. CONCLUSIONS:In cases of IBDI it is necessary to perform the operation under the supervision of an experienced surgeon who is specialized in the repair of bile duct injuries,and it is also necessary to detect and treat the injury as soon as possible to obtain a satisfactory outcome.

Catheter tract implantation metastases associated with percutaneous biliary drainage for extrahepatic cholangiocarcinoma

AIM： To estimate the incidence of catheter tract implantation metastasis among patients undergoing percutaneous transhepatic biliary drainage （PTBD） for extrahepatic cholangiocarcinoma, and to provide data regarding the management of this unusual complication of PTBD by reviewing cases reported in the literature. METHODS： A retrospective analysis of 67 consecutive patients who underwent PTBD before the resection of extrahepatic cholangiocarcinoma was conducted. The median follow-up period after PTBD was 106 too. The English language literature （PubMed, National Library of Medicine, Bethesda, MD, USA）, from .lanuary 1966 through December 2004, was reviewed. RESULTS： Catheter tract implantation metastasis developed in three patients. The cumulative incidence of implantation metastasis reached a plateau （6%） at 20 mo after PTBD. All of the three patients with implantation metastasis died of tumor progression at 3, 9, and 20 mo after the detection of this complication. Among the 10 reported patients with catheter tract implantation metastasis from extrahepatic cholangiocarcinoma （including our three patients）, two survived for more than 5 years after the excision of isolated catheter tract metastases. CONCLUSION： Catheter tract implantation metastasis is not a rare complication following PTBD for extrahepatic cholangiocarcinoma. Although the prognosis for patients with this complication is generally poor, the excision of the catheter tract may enable survival in selected patients with isolated metastases along the catheter tract.

Incidence of port-site metastasis after undergoing robotic surgery for biliary malignancies

AIM： To investigate the incidence of clinically detected port-site metastasis （PSM） in patients who underwent robotic surgery for biliary malignancies. METHODS： Using a prospective database, the patients undergoing fully robotic surgery for biliary malignan- cies between January 2009 and January 2011 were in- cluded. Records of patients with confirmed malignancy were reviewed for clinicopathological data and informa- tion about PSM. RESULTS： Sixty-four patients with biliary tract cancers underwent robotic surgery, and sixty patients met the inclusion criteria. The median age was 67 year （range： 40-85 year）. During a median 15-mo follow-up period, two female patients were detected solitary PSM after robotic surgery. The incidence of PSM was 3.3%. Pa- tient 1 underwent robotic anatomatic left hemihepa- tectomy and extraction of biliary tumor thrombi for an Klatskin tumor. She had a subcutaneous mass located at the right lateral abdominal wall near a trocar scar. Patient 2 underwent robotic pancreaticoduodenectomy for distal biliary cancer. She had two metachronous subcutaneous mass situated at the right lateral abdomi- nal wall under a same trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed meta- static biliary adenocarcinoma. CONCLUSION： The incidence of PSIVls after robotic surgery for biliary malignancies is relatively low, and biliary cancer can be an indication of robotic surgery.

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.

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.

Biliary tract tumors: past, present and future

Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction： obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU （response rate 20%） and gemcitabine （response rate of 13%-60%）, so they have been selected for further development in multiple phase II clinical trials to explore their efficacy and safety in combination with other agents. In a phase III clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.

Present status of biliary surgery in China

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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。

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.

胰胆管合流异常相关性胆囊癌研究进展

胰胆管合流异常(PBM)是一种先天性胰胆管畸形,常会引起反复发作的胆管炎、胰腺炎。越来越多的证据表明PBM是一种癌前病变,在胆囊癌(GBC)的发生和发展中起着重要的作用。由PBM所致GBC称为PBM相关性GBC。因此,PBM的早期识别及诊治对于降低GBC的风险至关重要。本文对PBM的概况和诊疗进展以及PBM相关性GBC的临床特征、发生机制及诊疗进展加以综述,旨在显示早期诊治PBM的临床价值,从而降低PBM相关性GBC发生率。

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。

Metal stent implantation for palliation of malignant biliary obstruction-a report of 57 cases

AIMS To report the first experience in China in the treatment of malignant biliary obstruction with expand- able metal stent which allows the insertion of an endo- prosthesis as large as one cm in diameter. METHODS Between April 1994 and May 1996,we implanted expandable metal stents in 57 patients with incurable malignant biliary obstruction,among whom 54 underwent endoscopic procedure and the other 3 re- ceived percutaneous transhepatic placement. RESULTS Insertion of the stent following guidewire positioning was successful in 95% of the patients. Two patients developed cholangitis after stent insertion and were successfully treated with conservative treatment. The jaundice was eliminated completely in 21 cases and markedly decreased in 23 cases within 2 weeks af- ter placement of the stent. Nine patients,however, had late cholangitis due to stent failure after a median interval of 14 days. Twenty-three cases underwent na- sobiliary transient drainage and 3 underwent plastic stent transient drainage prior to metal stent insertion. Transient drainage was believed to have the advan- tages of drainage pre-assessment and infection controlling. CONCLUSIONS Our results show that expandable metal stent is suitable for the irresectable malignant choledochal stenosis. It can eliminate the jaundice and improve the patient's life quality. To get the highest benefit,however,the indication should be strictly selected. And to get long-term patency,the proximal and distal end of the stent proceeding the tumor should be no shorter than 2cm. In the case of hilar cancer, Bismuth classification is greatly helpful for the choice of drainage site.

吲哚箐绿荧光成像技术在基层医院肝胆外科中的应用

吲哚箐绿(ICG)荧光染色在肝胆外科手术中的运用越来越广泛,近年来随着ICG荧光成像技术的快速发展及推广,使得肝胆外科精准化治疗有了清晰的导航指引作用。基层医院在复杂胆囊切除、复杂胆道结石手术及肝段精准切除中,ICG荧光成像技术能精准地识别解剖结构,缩短手术时间,避免手术损伤,减少术后并发症的发生,避免患者因术中损伤造成二次伤害。未来,ICG荧光成像技术的快速发展将会在胆道外科中显现更多的临床价值,对基层医院肝胆外科的发展有着重要意义。本文对ICG在基层医院肝胆外科中的应用进行综述。

老年人胆道术后心理弹性现状及影响因素分析

采取便利抽样法,应用一般资料调查表、疼痛视觉模拟量表、心理弹性量表、家庭功能评定量表,对唐山市4所养老机构胆道术后282名老年人调查胆道术后老年人心理弹性的情况及相关影响因素。调查结果显示胆道术后老年人的心理弹性处于中等偏下水平。利用多元线性回归分析显示,影响胆道术后老年人心理弹性的因素与婚姻状况、文化程度、月收入、慢性病、术后疼痛程度、住院费用有无困难、家庭功能有关。

修复时机对复杂腹腔镜胆囊切除术致医源性胆道损伤患者的影响分析

目的:探讨修复时机对复杂腹腔镜胆囊切除术(LC)致医源性胆道损伤患者的影响。方法:回顾性选择2021年1月-2023年11月兴化市中医院收治的60例医源性胆道损伤患者资料为研究对象,根据手术修复的时机将患者分为延迟修复组与非延迟修复组,每组30例。延迟修复组于损伤72 h后完成修复,非延迟修复组于损伤后72 h内完成修复,比较两组的Bismuth分型情况、手术情况及并发症发生情况。结果:两组Bismuth分型情况比较,差异无统计学意义(P>0.05)。非延迟修复组手术时间与术后住院时间均短于延迟修复组,差异均有统计学意义(P<0.05)。非延迟修复组并发症发生率为10.00%,低于延迟修复组的36.67%,差异有统计学意义(P<0.05)。结论:对存在复杂情况的LC手术患者,应警惕医源性胆道损伤风险,及时发现损伤并采取正确的修复方式,能够降低并发症的发生风险。

精准胆道外科理论引导下手术治疗胆囊癌的效果及对应激反应、肿瘤标志物水平的影响

目的分析精准胆道外科理论引导下手术治疗胆囊癌的效果及对应激反应、肿瘤标志物水平的影响。方法选择2020年1月至2022年2月医院收治100例胆囊癌患者为研究对象,以随机数字表法将其分为对照组、观察组,每组50例。对照组采用传统胆囊根治术治疗,观察组给予精准胆道外科理论引导下手术治疗。比较两组的治疗效果。结果观察组的手术时长长于对照组,术中出血量少于对照组,淋巴结清扫数量多于对照组,首次排气时间、住院时间短于对照组(P<0.05)。术后24 h,观察组的促肾上腺皮质激素(ACTH)、皮质醇(Cor)水平低于对照组(P<0.05)。术后2周,观察组的癌胚抗原(CEA)、糖类抗原125(CA125)及甲胎蛋白(AFP)水平低于对照组(P<0.05)。结论精准胆道外科理论引导下手术治疗胆囊癌不仅可缓解机体应激反应,调节肿瘤标志物水平,还有助于提升手术效果,缩短患者住院时间,值得推广。

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.