| Part 1 Efficacy and safety of transcatheter arterial infusion for pancreatic cancerBackground and aim:Pancreatic cancer are common among gastrointestinal malignancy and the seventh cause of cancer related death.About 80%of patients have unresectable cancer at the time of diagnosis and 5-year survival rate is only about 3%.Systemic chemotherapy is the standard of care for patients with advanced disease,while systemic chemotherapy is only recommended for selected patients based on age,comorbidities,and performance status due to chemotoxicity.In these patients,tumor depletion,pain,anorexia,and cachexia may lead to ineligibility for systemic chemotherapy in some patients.In addition,mutations of key gene,signaling pathway abnormality,and hypoxia of microenvironment may lead to drug resistance and refractory to systemic chemotherapy.Managements for patients ineligible for or refractory to systemic chemotherapy are extremely limited,and the median overall survival for these patients managed with best supportive care was reported with only 2.3 months.Transcatheter arterial infusion(TAI)improves the local concentration of chemotherapeutic drug and reduces the systemic concentration,with reduced complications and increased tolerance in patient.TAI is believed to delay local tumor progression and the occurrence of symptoms(i.e.pain),thereby improving the quality of life and survival of the patients.Furthermore,hepatic arterial infusion during TAI may also be an effective treatment for patients with liver metastases.In addition,drugs failed in systemic chemotherapy,may still effective in TAI.Therefore,TAI is promising for the palliation of pancreatic cancer in patient ineligible for or refractory to systemic chemotherapy.However,relevant study is still lacking.The aim of this study is to evaluate the efficacy and safety of TAI for the treatment of pancreatic cancer in patient ineligible for or refractory to systemic chemotherapy.Materials and Methods:The medical records of 115 consecutive patients(mean age,58.9 years;71 males)with documented pancreatic cancer ineligible for or refractory to systemic chemotherapy and underwent TAI between February 2007 and January 2017 were reviewed.Results:A total of 224 TAI sessions[mean,1.9(range 1-8)]were performed.Technical success rate was 100%.Disease control(i.e.,complete response,partial response,and stable disease)was achieved in 72(62.6%)patients.The median progression-free survival and median overall survival were 56[interquartile range(IQR),32-98]days and 147(IQR,96-223 days)days,respectively.Subgroup analysis revealed disease control,progression-free survival,and overall survival were significantly improved in patients with an Eastern Cooperative Oncology Group score of?1 compared with those in patients with an Eastern Cooperative Oncology Group score of 2(all p<0.001)and in patients who received>1 sessions of TAI compared with that in patients who received only 1 session of TAI(p=0.012,<0.001,and=0.002,respectively).A major complication in the form of cerebral infarction occurred in 1(0.9%)patient 1 day after the procedure.This patient was treated with pharmacotherapy and recovered without permanent adverse sequelae.No other major complications were observed.Minor complications occurred in 53.0%of the patients,including transient abdominal pain(30.4%),nausea/vomiting(21.7%),fever(1.7%)and thrombocytopenia(0.9%).All were self-limited or relieved after symptomatic treatment.Conclusions:TAI may be effective and safe for the treatment of pancreatic cancer in patient ineligible for or refractory to systemic chemotherapy.Eastern Cooperative Oncology Group score and session of TAI were prognostic factors.Part 2 Establishment of biliary metal stent model in ratBackground and aim:Biliary obstruction are the occlusion of biliary duct caused by various reasons,and presenting with scleral yellowing of skin,hyperbilirubinemia and biliary dilation.According to the pathogenesis,biliary obstruction is divided into benign biliary obstruction and malignant biliary obstruction.The incidence of malignant biliary obstruction in patients with pancreatic cancer is up to 70%.Biliary stent is effective for the relief of biliary obstruction.However,stent restenosis commonly occurred shadowing the patency of the stent with 5-9 months for metal stent and 2-5 months for plastic stent.Reintervention increases the patient's suffering.Clinical and animal model studies had shown that stent restenosis was related to local biliary epithelial cell proliferation,inflammatory reaction and fibrosis after stent implantation.However,in some cases,such pathological findings and stent restenosis were not observed and replaced with a single layer of epithelioid cells covered inside the stent.The molecular mechanism is still not clear.Currently,the animal models of biliary stent are established in large animals(i.e.dogs,pigs),which are difficult to raise,expensive,and lack of relevant experimental antibodies,limiting the study of molecular mechanism.The establishment of an appropriate animal model is critical for studying the mechanism of stent restenosis.Rat is homologous with human and carries the advantage of low cost,convenient feeding and multitudinous experimental antibodies,making rat the ideal animal for studying the mechanism of stent restenosis.However,the diameter of the common bile duct in rat is only about 1mm.Due to the lacking of relevant metal stent,biliary metal stent model in rat was never established and reported.In this study,therefore,self-made nitinol alloy braided self-expandable metal stent was used to establish biliary metal stent model in rat.This model may provide further possibility for studying the mechanism of biliary stent restenosis.Materials and Methods:Using 0.075mm diameter nitinol alloy wire,a self-expandable metal stent was established with the diameter of 1.8mm and length of 6mm.Twenty male Sprague Dawley rats(380-400g)were 1:1 randomized to the stent group and the sham group.In the stent group,the common bile duct of the rats was cut open and self-expandable metal stent was implanted.In the sham group,the common bile duct was cut open in the corresponding site and then sutured.The rat model was evaluated by imaging 1 week after the procedure.The common bile duct was harvested 6 months after the procedure for gross observation and microscopic examination after hematoxylin eosin staining.Technical success is defined as successful implantation of a biliary stent(imaging or autopsy confirmed)in the common bile duct.The model success rate was defined as technical success along with corresponding histological response of the biliary duct confirmed via subsequent HE staining.Results:Technical success rate was 90%(9/10,1 malposition)and complication rate was 44%(4/9,3 death,1 bile duct obstruction at suture site)in the stent group.Procedure related death were due to hemorrhagic shock,bile leakage,and biliary peritonitis.Technical success rate was 100%(10/10)and complication rate was 10%(1/10,1 death)in the sham group.Procedure related death were due to bile leakage and bile peritonitis.After 6 months,all the rats in the stent group and the sham group had tissue adhesion,structural disorder and peritoneal aggregation in the hepatic hilum area.The common bile duct adhered steadily to the surrounding tissues.Of the 5 rats in the stent group,common bile duct lumen was obviously dilated,with increased epithelial cell layers,submucosal fibrous connective tissue hyperplasia and inflammatory cell infiltration.The model success rate was 100%(5/5).In the sham group,the common bile duct was consisted of monolayer epithelial cell,well-defined muscle contour,and is comparable with normal common bile duct.Conclusions:Using expandable metal stent,biliary metal stent model in rat was successfully established.Epithelial hyperplasia,submucosal fibrous connective tissue hyperplasia,and inflammatory cell infiltration was observed 6 months after stent implantation.This study may provide a rat model for further exploring the mechanism of stent restenosis of biliary stent. |
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