Selection And Efficacy Evaluation Of Endoscopic Treatment For Different Phase Ampullary Tumors

Tumor arising from the ampulla of Vater is relatively rare;however,the diagnosis rate is increasing.Most benign ampullary lesions are adenomatous in origin with a potential evolution to carcinoma,so resection is recommended.Endoscopic papillectomy（EP）has gradually developed to replace surgical resection as the first-line plan for ampullary benign lesions,and its indication has expanded to part of early ampullary adenocarcinoma.Nevertheless,the high recurrence rate still limits its application.EP has less trauma than the surgical operation,while it owned many more adverse events than the endoscopic resection of gastrointestinal tumors in other locations,due to the unique anatomical location.Therefore,it remains a tricky topic to minimize the postoperative complications and recurrence.Additionally,for ampullary carcinoma,a considerable proportion of patients could not receive pancreaticoduodenectomy owing to the comorbidity,advanced age or/and tumor stage.Currently,studies focused on the treatment of non-surgical ampullary carcinoma are rare.Biliary obstruction is quite common in these patients,seriously affecting life quality and overall survival.Stent implantation under endoscopy is the preferred palliative treatment.Notwithstanding,repeated stent stenosis or occlusion challenges a lot.Iodine-125(¹²⁵I)has been widely used in malignant tumors and shown to prolong stent patency and survival in malignant obstructive jaundice.Currently,published research on non-surgical ampullary carcinoma or the application of ¹²⁵I particles in ampullary carcinoma is rare.Recently,the minimally invasive endoscopic techniques developed quickly into the super minimally invasive technology,and gradually formed a brand new discipline-endoscopic surgery.This technique has been widely used in the complete resection of common early gastrointestinal carcinoma,submucosal and muscularis propria lesions,but there are still many problems to be solved in the treatment of ampullary tumors（such as high adverse events and recurrence rate after EP,and the management of unresectable ampullary tumors）.In addition,the selection of treatment plan for ampullary tumor depends not only on the pathological type of tumor（benign and malignant）,but also on the size and invasion of tumor.Currently,there is no unified staging plan for ampullary tumor based on treatment mode.In this study,ampullary tumors were divided into three phases according to different treatment methods:Phase I,minimally invasive resection phase,including ampullary benign tumors that can be resected under endoscope and part of T1 ampullary malignant tumors;Phase II,Surgical radical resection phase,for ampullary benign or malignant tumors treated by surgical radical resection;Phase III,Palliative treatment（unresectable）phase,for patients with ampullary carcinoma who are not qualified for radical surgery due to stage,advanced age,complications or personal desire.This study aimed to explore the factors influencing the efficacy of endoscopic resection for ampullary tumors in phase I（minimally invasive resection phase）with minimally invasive technique as the entry point,to provide a basis for reducing the incidence of postoperative adverse events,residual and recurrence rates,so as to improve the safety and effectiveness of EP.The purpose of this study was also to explore the application value and efficacy of ¹²⁵I seed implantation as palliative treatment for phase III（unresectable phase or palliative treatment phase）ampullary tumor.Part 1 Endoscopic papillectomy for ampullary tumor in the minimally invasive resectable phase:adverse events and long-term outcomesAim:To study the risk factors for adverse events,remnant and recurrence after EP are presented to establish preventive measures.Methods:A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study.Related factors were analyzed by logistic or Cox regression.Results:Adverse events were experienced in 64 patients（36.99%）,included 33 bleeding,26post-endoscopic papillectomy acute pancreatitis（PPAP）,10 acute cholangitis,and 4 perforation patients.No process-related death occurred.Multivariate analysis identified intraoperative bleeding（yes>no:OR:4.38,95%CI 1.87-11.15,P=0.001）and endoscopic closure（not done>done:OR:0.25,95%CI 0.10-0.58,P=0.001）as independent factors associated with bleeding after EP.Lesion size（≥3cm）was shown as an independent factor associated with intraoperative bleeding（OR:4.25,95%CI 1.21-16.44,P=0.028）.Age was an independent factor for PPAP（OR:0.96,0.91-0.99,P=0.038）.Residual tissue was observed in 11 cases during the first 3months follow-up.The two independent factors were positive vertical margin（OR:13.05,95%CI:2.33-102.43,P=0.005）and extension to pancreatic or/and bile duct（OR:6.21,95%CI:1.28-31.67,P=0.023）.Recurrence was observed in 23 patients（16.91%）during the follow-up（median:39.5months,IQR:21-60months）.positive vertical margin（HR:10.05,95%CI:2.67-37.81,P=0.001）,and adenocarcinoma（HR:9.49,95%CI:1.86-48.36,P=0.007）were independent factors.Conclusions:This retrospective evaluation found that lesion size（≥3cm）may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.Endoscopic closure might reduce the risk of bleeding,while intraoperative bleeding might increase the risk.Advanced age may be a protective factor for PPAP.Pancreatic duct stent did not prove to be of a protective effect in this study.The positive vertical margin was an independent predictor of residual within three months after EP and recurrence,while the extension to pancreatic or/and bile duct was an independent risk factor only for residual.Tumor type does not affect postoperative residual,but high-grade intraepithelial neoplasia（HGIN）and adenocarcinoma were independent predictors of recurrence.EP is safe and effective in ampullary adenoma.However,it is still controversy about ampullary adenocarcinoma.For patients with positive vertical resection margin,extension to pancreatic or/and bile duct,and HGIN or adenocarcinoma in postoperative pathology,endoscopic surgery or high-frequency follow-up should be considered in time.Part 2 Role of EUS-guided iodine-125 seed implantation in ampullary cancer patients during palliative treatment phaseAims: To investigate the role of ¹²⁵I seed implantation under endoscopic ultrasonography（EUS）in patients with inoperable ampullary carcinoma after relief of obstructive jaundice.Methods: A total of 44 patients with obstructive jaundice due to unresectable ampullary carcinoma from January 1,2010,to October 31,2020,were enrolled.Eleven underwent implantation of ¹²⁵I seeds under EUS after receiving a biliary stent placement via endoscopic retrograde cholangiopancreatography（ERCP）（treatment group）,and 33 received a stent alone via ERCP（control group）.Cox regression was used in this single-center retrospective comparison study.Results: Median maximum intervention interval for biliary obstruction was 381 days（IQR: 204-419 days）in the ¹²⁵I treatment group and 175 days（IQR: 126-274 days）in the control group（P<0.05）.Stent occlusion rates at 90 days and 180 days in the control group were 12.9% and 51.6%,respectively.No stent occlusion occurred in the treatment group.Patients in the treatment group obtained a longer median survival time（median,26 vs.13 months;P<0.01）and prolonged duodenal obstruction（median,20.50 vs.11 months,P<0.05）.None of the brachytherapy-related grade 3 or 4 adverse events occurred.Conclusions: Longer intervention interval for biliary obstruction and survival,better stent patency,and prolonged time to duodenal obstruction could be achieved by implantation of ¹²⁵I seed combined biliary stent in patients with unresectable ampullary cancer.