Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma

BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous,stable drug release locally and inhibits tumor growth effectively in vitro and in vivo.It can also be used safely in normal porcine bile ducts.We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma:A meta-analysis

AIM:To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma(ECC)through a meta-analysis of clinical observational studies.METHODS:A literature search was conducted using Embase and MEDLINE databases from inception to 31May 2013 without language limitations,and by manually searching the references of retrieved articles.Casecontrol and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included.The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale.Summary relative risks and corresponding95%CI were calculated using a random-effects model.Publication bias was assessed by Begg’s funnel plot and Egger’s test.RESULTS:A total of 12 eligible articles(11 case-control studies and one cohort study)were included in this meta-analysis.Eleven studies reported the association between smoking and ECC.Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers(summary RR=1.23;95%CI:1.01-1.50).This correlation was present in population-based studies(n=5;summary RR=1.47;95%CI:1.06-2.05)but not in hospital-based studies(n=6;summary RR=1.10;95%CI:0.88-1.37)and in non-Asian regions(n=7;summary RR=1.39;95%CI:1.03-1.87)but not in Asia(n=4;summary RR=1.08;95%CI:0.85-1.38).Seven studies reported an association between consuming alcohol and ECC.Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol(summary RR=1.09;95%CI:0.87-1.37).There was moderate heterogeneity among the studies and no evidence of publication bias.CONCLUSION:Smoking is associated with an increased risk of ECC,but alcohol consumption is not.Further population-based studies,particularly cohort studies,are warranted to enable definitive conclusions.

Current role of hepatopancreatoduodenectomy for the management of gallbladder cancer and extrahepatic cholangiocarcinoma:A systematic review

BACKGROUND Hepatopancreatoduodenectomy(HPD)is the simultaneous combination of hepatic resection,pancreaticoduodenectomy,and resection of the entire extrahepatic biliary system.HPD is not a universally accepted due to high mortality and morbidity rates,as well as to controversial survival benefits.AIM To evaluate the current role of HPD for curative treatment of gallbladder cancer(GC)or extrahepatic cholangiocarcinoma(ECC)invading both the hepatic hilum and the intrapancreatic common bile duct.METHODS A systematic literature search using the PubMed,Web of Science,and Scopus databases was performed to identify studies reporting on HPD,using the following keywords:‘Hepatopancreaticoduodenectomy’,‘hepatopancreatoduodenectomy’,‘hepatopancreatectomy’,‘pancreaticoduodenectomy’,‘hepatectomy’,‘hepatic resection’,‘liver resection’,‘Whipple procedure’,‘bile duct cancer’,‘gallbladder cancer’,and‘cholangiocarcinoma’.RESULTS This updated systematic review,focusing on 13 papers published between 2015 and 2020,found that rates of morbidity for HPD have remained high,ranging between 37.0%and 97.4%,while liver failure and pancreatic fistula are the most serious complications.However,perioperative mortality for HPD has decreased compared to initial experiences,and varies between 0%and 26%,although in selected center it is well below 10%.Long term survival outcomes can be achieved in selected patients with R0 resection,although 5–year survival is better for ECC than GC.CONCLUSION The present review supports the role of HPD in patients with GC and ECC with horizontal spread involving the hepatic hilum and the intrapancreatic bile duct,provided that it is performed in centers with high experience in hepatobiliarypancreatic surgery.Extensive use of preoperative portal vein embolization,and preoperative biliary drainage in patients with obstructive jaundice,represent strategies for decreasing the occurrence and severity of postoperative complications.It is advisable to develop internationally-accepted protocols for patient selection,preoperative assessment,operative technique,and perioperative care,in order to better define which patients would benefit from HPD.

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 mo. The English language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), from January 1966through 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.

Adjuvant surgery for advanced extrahepatic cholangiocarcinoma

Patients with StageⅣcholangiocarcinoma are currently not considered to be surgical candidates and are typically offered systemic chemotherapy.Recently,several novel systemic chemotherapy regimens have allowed an initially unresectable cholangiocarcinoma to be resectable.The aim of this article is to present the usefulness of adjuvant surgery in a case of advanced cholangiocarcinoma that was successfully treated with gemcitabine.A 72-year-old man was diagnosed with distal cholangiocarcinoma with liver metastases(cT2N0M1,StageⅣ).He underwent metal stent placement in the duodenum to alleviate jaundice.After 18courses of chemotherapy using gemcitabine without severe drug toxicities,a computed tomography scan showed that the liver metastases in S6 and S7 had disappeared.The patient underwent subtotal stomachpreserving pancreaticoduodenectomy and lymph node dissection.The pathological stage was pT2N0M0,StageⅠB.The patient underwent 6 cycles of adjuvant chemotherapy using gemcitabine.The patient is alive and well 6 years and 9 mo after the diagnosis.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma:A case report and review of literature

BACKGROUND Neuroendocrine carcinoma(NEC)of the extrahepatic bile duct is very rare,and the treatment and prognosis are unclear.Herein,we report the case of a middleaged female with primary large cell NEC(LCNEC)of the common hepatic duct combined with distal cholangiocarcinoma(dCCA).Additionally,after a review of the relevant literature,we summarize and compare mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.CASE SUMMARY A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months.Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign.Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels.Imaging examination revealed node dissection was performed,and hepatic duct tumours were unexpectedly found during surgery.Pathology suggested poorly differentiated LCNEC(approximately 0.5 cm×0.5 cm×0.4 cm),Ki-67(50%),synaptophysin+,and chromogranin A+.dCCA pathology suggested moderately differentiated adenocarcinoma.The patient eventually developed lymph node metastasis in the liver,bone,peritoneum,and abdominal cavity and died 24 months after surgery.Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.CONCLUSION The prognosis of MiNEN and pure NEC alone is different,and the selection of treatment options needs to be differentiated.

Evaluation of surgical approach for extrahepatic cholangiocarcinoma

BACKGROUND: The incidence of extrahepatic cholangiocarcinoma increases in recent years. But the diagnosis and treatment are still troublesome to surgeons. This study was designed to explore the value of surgical approach in the treatment of extrahepatic cholangiocarcinoma. METHODS: We retrospectively analyzed the clinical data of 135 patients with extrahepatic cholangiocarcinoma who had been treated in our hospital from January 1992 to December 2006. RESULTS: The ratio of extrahepatic cholangiocarcinoma to biliary duct diseases was 1.81%. The rates of total resection and radical resection were 70.75% (75/106) and 56.60% (60/106), respectively. The overall 1-, 3-, 5-year survival rates were 46.93%, 37.33% and 18.75%, respectively. The 1-, 3-, 5-year survival rates were better in the radical resection group (74.94%, 55.74% and 41.27%, respectively) than in the palliative resection group(42.86%, 26.79% and 26.79%, respectively) (P<0.05). The survival rates of patients who had undergone palliative resection were higher than those of patients who had been subjected to palliative drainage or non-operation: 1-, 3-,5-year survival rates were 42.86%, 26.79%, 26.79% vs. 23.33%, 6.67%, 0 or 17.86%, 0, 0 (P<0.05). While the survival rates were not significantly different between palliative drainage and nonoperation (P<0.05). Multivariate analysis revealed that the histopathological grades, TNM stages and modalities were key factors influencing the outcome. CONCLUSIONS: The outcome of the patients with extrahepatic cholangiocarcinoma is still not optimistic. Radical resection is the first choice for the treatment of tumors.

Significance of dysplasia in bile duct resection margin in patients with extrahepatic cholangiocarcinoma:A retrospective analysis

BACKGROUND Radical resection is the only indicator associated with survival in extrahepatic cholangiocarcinoma(EHCC).However,limited data are available regarding the implications of dysplasia at the resection margin following surgery.AIM To evaluate the prognostic significance of dysplasia-positive margins in patients diagnosed with EHCC.METHODS We reviewed the records of patients who had undergone surgery for EHCC with curative intent between January 2013 and July 2017.We retrospectively analyzed the clinicopathological data of 116 patients followed for longer than 3 years.The status of resection margin was used to classify patients into negative low-grade dysplasia(LGD)and high-grade dysplasia(HGD)/carcinoma in situ(CIS)categories.RESULTS Based on postoperative status,72 patients underwent resection with negative margins,19 had LGD-positive margins,and 25 showed HGD/CIS-positive margins.The mean survival rates of the patients with negative margins,LGD margins,and HGD/CIS margins were 49.1±4.5,47.3±6.0,and 20.8±4.4 mo,respectively(P<0.001).No difference in survival was found between groups with LGD margins and negative margins(P=0.56).In the multivariate analysis,age>70 years and HGD/CIS-positive margins were significant independent factors for survival(hazard ratio=1.90 and 2.47,respectively).CONCLUSION HGD/CIS margin in resected EHCC is associated with a poor survival.However,the LGDpositive resection margin is not a significant indicator of survival in patients with EHCC.

Expression of histone methyltransferase G9a and clinical significance in extrahepatic cholangiocarcinoma

Objective: To investigate the mRNA and protein expression of histone methyltransferase G9a and its clinical significance in extrahepatic cholangiocarcinoma. Methods: Using RT-PCR and Western Blotting to detect the expression of G9a at the level of mRNA and protein in 48 tumor samples and 39 control tissues. Results: The mRNA and protein expres- sion of G9a in extrahepatic cholangiocarcinoma was higher than control statistically (P < 0.05) and positively correlated with lymph metastasis (P < 0.05) and TNM stage (P < 0.01). Conclusion: The significant difference of G9a expression between tumors and control implicated that the important role of histone methylation disruption resulted from increased G9a expression in extrahepatic cholangiocarcinoma.

Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Neoadjuvant chemoradiotherapy before resection of perihilar cholangiocarcinoma: A systematic review

Background: Treatment with neoadjuvant chemoradiotherapy followed by liver transplantation yields promising results in perihilar cholangiocarcinoma (PH-CCA). This study reviews the literature to assess whether there is evidence to justify modern phase Ⅱ studies of neoadjuvant chemoradiotherapy prior to resection of PH-CCA.Data sources: A systematic review of the literature for reports of patients undergoing resection of PH- CCA after neoadjuvant chemoradiotherapy was performed using MEDLINE and EMBASE databases for the period between 1990 and 2019. The keywords and MeSH headings "hilar cholangiocarcinoma", "Klatskin", "chemoradiotherapy" and "chemotherapy" were used. Data were extracted on demographic profile, dis- ease staging, chemoradiotherapy protocols, complications and outcome. Risks of bias were assessed using Cochrane methodology. Results: There were seven reports on this topic, with median recruitment period of 14 (range 4–31) years. The total number of patients in these studies was 87. Interval from completion of neoadjuvant treatment to surgery varied from 3 days to 6 months. Resection was by hepatectomy with three studies reporting an R0 rate of 100%, 24% and 63%, respectively. Three studies reported histopathological evidence of prior treatment response. There were two treatment related deaths at 90 days. Median survival was 19 (95% CI: 9.9–28) months and 5-year survival 20%. Conclusions: There are potential benefits of treatment on both R0 rate and complete response in resected specimens. Scientific equipoise exists in relation to neoadjuvant chemoradiotherapy for PH-CCA.

Radiation therapy for extrahepatic bile duct cancer: Current evidences and future perspectives

Extrahepatic bile duct cancer (EBDC) is a rare malignancy that involves neoplastic changes extending from both hepatic ducts to the common bile duct. The treatment of choice is surgical resection, but the predominant pattern of initial treatment failure is locoregional recurrence. Accordingly, adjuvant radiotherapy has been administered after surgical resection based on these rationales. At this time, there is minimal evidence supporting adjuvant radiotherapy, because there have been no phase III trials evaluating its benefit. Relatively small retrospective studies have tried to compare outcomes associated with EBDC treated with or without radiotherapy. We aimed to review studies investigating adjuvant radiotherapy for resected EBDC. Because less than onethird of EBDC cases are amenable to curative resection at diagnosis, other locoregional treatment modalities need to be considered, including radiotherapy. The next aim of this review was to summarize reports of definitive radiotherapy for unresectable EBDC. Patients with advanced EBDC often experience biliary obstruction, which can lead to jaundice and progress to death. Biliary stent insertion is an important palliative procedure, but stents are prone to occlusion after subsequent ingrowth of the EBDC. Radiotherapy can be effective for maintaining the patency of inserted stents. We also reviewed the benefit of palliative radiotherapy combined with the biliary stent insertion. Lastly, we discuss the existing gaps in the evidence supporting radiotherapy in the management of EBDC.

EXPLORE ON DIAGNOSTIC AND PROGNOSTIC VALUES OF EXTRAHEPATIC CHOLANGIOCA RCINOMA: UTILITY OF SERUM CA19-9 AND SERUM CEA

Objective To evaluate th e validity of a serum carbohydrate antigen 19-9(CA19-9) determination in the dia gnosis of extrahepatic cholangiocarcinoma(EHCC). Methods Serum CA19-9 concentration and serum carcinoembryonic antigen(CEA) concentration wer e prospectively measured by an immunoradiometric assay without knowledge of the clinical diagnosis in patients with EHCC (n=51), benign biliary diseases ( n=42), and healthy individuals (n=15). Using a receiver operating characte ristic (ROC) curve define a new strategy for interpreting CA19-9 and CEA in EHC C. Results The sensitivity of CA19-9 and CEA in diagnosing E HCC were 86.3% (44/51) and 25.5%(13/51), respectively. When compared with the be nign biliary diseases group, the true negative rates of serum CA19-9 and serum CEA were 85.7% (36/42) and 95.2%(40/42), respectively. The false positive rates of serum CA19-9 and serum CEA were 14.3 %( 6/42) and 4.8 %( 2/42), whereas the accuracy of serum CA19-9 and serum CEA were 57.0%(53/93) and 86.0%(80/93), resp ectively. Serum CA19-9 concentration and serum CEA concentration were significa ntly elevated (P<0.01 and P<0.05) in patients with EHCC \[(489.6±150.2 )kU·L -1 and (22.0±2.4)μg·L -1)\] compared with patients with beni gn biliary diseases\[ (20.2±4.7) kU·L -1 and (14.8± 0.8)μg·L -1)\] and healthy individuals \[(12.8±3.7) kU·L -1 and (11.5±3.4μ g·L -1)\]. The ROC curves analysis showed that the area under the ROC cu rve(AUC)of serum CA19-9 and serum CEA were 0.942 (P<0.001) and 0.516 (P >05), respectively. In 22 patients undergoing curative resection of EHCC, the mean serum CA19-9 concentration decreased from preoperative level of (456.6±1 20.4) kU·L -1 to postoperative level (62.8±17.3) kU·L -1(P< 0. 001). The outcomes showed that serum CA19-9 had greater diagnosis performance s than serum CEA. Conclusion Serum CA19-9 is an effective tum or marker in diagnosing of cholangiocarcinoma, deciding whether the tumor has be en radically resected and monitoring effect of treatment

Stereotactic radiotherapy for intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma(iCCA)is an aggressive malignancy with an increasing incidence worldwide and poor prognosis,despite several advances and continuous efforts to develop effective treatments.Complete surgical resection is the mainstay of treatment and offers a potentially curative option,but is only possible in less than a third of patients,owing to advanced disease.Chemotherapy is a well-established treatment in the adjuvant and palliative setting,however,confers limited benefit.Conventional radiotherapy is challenging due to local toxicity.With recent advances in stereotactic ablative radiotherapy(SABR),it is now possible to focus ablative beams of radiotherapy precisely aimed at tumours to minimise damage to surrounding viscera.This review details the history,technical background and application of SABR to iCCA,with directions for future research suggested.

Primary signet-ring cell carcinoma of the extrahepatic bile duct:A case report

BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round or oval,and the nuclear deviations give the cells a signet ring-like appearance.SRCC often originates in the gastrointestinal tract,especially in the stomach.However,primary SRCC of the extrahepatic bile duct is extremely rare.Therefore,little is known about its epidemiology,treatment,and prognosis.CASE SUMMARY An 82-year-old female was admitted with abdominal pain,jaundice,and skin pruritus for 2 mo.She had no specific family history.Physical examination presented normal vital signs,icteric sclera,visible jaundice,and mild tenderness in the right upper abdominal quadrant.Tumor-related cell markers were within normal values.Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct,strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver.In addition,the lymph nodes in the hepatic hilum area,the pancreatic head area,and around the abdominal aorta were enlarged.Thus,a preoperative diagnosis of cholangiocarcinoma was established.To alleviate jaundice and prolong the overall survival,percutaneous transhepatic cholangiopancreatic drainage(PTCD)was performed.During the operation,segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed.Furthermore,a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion.The pathological diagnosis of the biopsy was SRCC.Finally,a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic,PTCD,and pathological characteristics.The tumor was diagnosed as T3N1M1 stage IV.Despite our aggressive approach,the patient died of liver failure after 1 mo.CONCLUSION This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date.

Occurrence of seeding metastases in resectable perihilar cholangiocarcinoma and the role of low-dose radiotherapy to prevent this

BACKGROUND Preoperative biliary drainage in patients with presumed resectable perihilar cholangiocarcinoma(PHC)is hypothesized to promote the occurrence of seeding metastases.Seeding metastases can occur at the surgical scars or at the site of postoperative drains,and in case of percutaneous biliary drainage,at the catheter port-site.To prevent seeding metastases after resection,we routinely treated PHC patients with preoperative radiotherapy(RT)for over 25 years until January 2018.AIM To investigate the incidence of seeding metastases following resection of PHC.METHODS All patients who underwent resection for pathology proven PHC between January 2000 and March 2019 were included in this retrospective study.Between 2000-January 2018,patients received preoperative RT(3×3.5 Gray).RT was omitted in patients treated after January 2018.RESULTS A total of 171 patients underwent resection for PHC between January 2000 and March 2019.Of 171 patients undergoing resection,111 patients(65%)were treated with preoperative RT.Intraoperative bile cytology showed no difference in the presence of viable tumor cells in bile of patients undergoing preoperative RT or not.Overall,two patients(1.2%)with seeding metastases were identified,both in the laparotomy scar and both after preoperative RT(one patient with endoscopic and the other with percutaneous and endoscopic biliary drainage).CONCLUSION The incidence of seeding metastases in patients with resected PHC in our series was low(1.2%).This low incidence and the inability of providing evidence that preoperative low-dose RT prevents seeding metastases,has led us to discontinue preoperative RT in patients with resectable PHC in our center.

小视野扩散加权成像ADC值评估肝外胆管癌淋巴血管侵犯的应用价值

目的探索基于小视野扩散加权成像(DWI)表观扩散系数(ADC)值对肝外胆管癌淋巴血管侵犯(LVI)的应用价值。方法回顾性分析经手术病理证实的54例肝外胆管癌的临床及影像学资料,术前均行常规DWI及小视野DWI(r-FOV DWI),两名高年资放射影像诊断医师对常规DWI和小视野DWI图像质量进行5级李克特量表评分,并比较两组图像病灶区信噪比(SNR)、对比信噪比(CNR)和ADC值。根据病理资料分为LVI阳性组和LVI阴性组,分别比较两组间常规和小视野ADC值的差异,以受试者工作特征(ROC)曲线评估常规ADC值和小视野ADC值对LVI的诊断效能。结果小视野DWI图像质量在主观评分、SNR、CNR比较中均好于常规组,且小视野ADC值小于常规ADC值,差异均有统计学意义(P<0.05)。LVI阳性组中常规组ADC值和小视野ADC值均小于LVI阴性组,差异具有统计学意义(P<0.05)。常规组ADC值(<1.217×10^(-3)mm^(2)/s)诊断LVI阳性的曲线下面积(AUC)为0.746[95%CI(0.609,0.882),P<0.05],其敏感度及特异度分别为75.0%、73.5%;小视野组ADC值(<1.092×10^(-3)mm^(2)/s)诊断LVI阳性的AUC为0.932[95%CI(0.866,0.999),P<0.05],其敏感度及特异度分别为95.0%、85.3%。两组AUC值差异有统计学意义(P<0.05)。结论小视野DWI成像ADC值较常规ADC值对于预测肝外胆管癌LVI具有更好的诊断价值。

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.

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.

Pathological aspects of so called "hilar cholangiocarcinoma"

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group.However,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar CC.Grossly,a major distinction can be made between papillary and non-papillary tumors.Histologically,most hilar CCs are well to moderately differentiated conventional type(biliary) carcinomas.Immunohistochemically,CK7,CK20,CEA and MUC1 are normally expressed,being MUC2 positive in less than 50% of cases.Two main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is reviewed.Most(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring cells.IPNB was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.