Clinical Evaluation Of Minimally Invasive Interventional In Diagnosis And Treatment Of Pancreatic Cancer By Multimodality Imaging Guidance

Part ?Comparison between MRI-guided and CT-guided Percutaneous Needle Biopsy for Diagnosis of Pancreatic LesionsIntroductionThe high mortality rate of pancreatic cancer is due to the lack of reliable early detectionof precancerous lesions and early invasive pancreatic cancer,as well as the relative poor efficacy of systemic chemotherapy.Imaging examination is an important method for the preliminary detection of pancreatic lesions,and histopathological diagnosis is the gold standard of final diagnosis.However,only less than 40%of patients who were diagnosed with pancreatic cancer were histologically validated,and it mainly diagnosed with surgery and pathology.Pathological biopsy can be obtained through open surgery,percutaneouspuncture,endoscopicultrasonography(EUS)or laparoscopic.The advantages of percutaneous biopsy are high accuracy,less trauma and fewer complications,and it can be guided with ultrasound,CT and MRI.Interventional magnetic resonance imaging(IMRI)has been developing rapidly in recent years.MRI-guided percutaneous biopsy with its advantages of excellent soft tissue contrast,any planar imaging capability,vascular emptying effect,functional imaging aids and no ionization radiation has been successfully applied to multiorgan pathology,achieving good diagnostic accuracy,but its application in pancreatic lesions have not been reported.ObjectiveThis study retrospectively analyzed the data of pancreatic lesions biopsy guided with MRI and CT,compared the sensitivity,specificity,positive predictive value,negative predictive value and the incidence of complications of pancreatic biopsy guided by CT and MRI,as to explore the accuracy and safety of MRI-guided pancreatic lesions biopsy.Materials and MethodsRetrospectively analyze data of 73 patients with pancreatic occupying lesions,and they were histopathological diagnosed by biopsy guided by CT or MRI from January 2015 to June 2016.CT-guided percutaneous needle biopsy patients were from the department of interventional radiology of Anhui Provincial Hospital,MRI-guided percutaneous needle biopsy patients were from the department of interventional MRI,Shandong provincial medical imaging research institute.The group of CT-guided includes 42 cases,and the group of MRI-guided includes 31 cases.Criteria for selected cases:(1)patients need clear diagnosis before surgery;(2)patients with pancreatic cancer who plan to do chemotherapy or chemoradiotherapy were with no indication of surgical resection,which were diagnosed with clinical and imaging;(3)suspected pancreatic solid mass were diagnosed with clinical and imaging,and lesions can be seen in images of CT or MRI,and the maximum diameter of the lesion measured ? 2 cm.Criteria for exclusive cases:(1)severe coagulation dysfunction(international standard ratio INR>1.5,or activated partial thromboplastin time twice or more than the normal time,or platelet count<50000 cells/cubic millimeter);(2)cystic part of the disease>25%;(3)a large number of ascites;(4)can not suspend anticoagulant therapy;(5)pregnancy or mental disorders;(6)refused to sign informed consent.Percutaneous needle biopsy process:before the biopsy,with CT/MRI enhanced scan images,confirm the location of the lesion and the relationship with the adjacent blood vessels,intestine and other adjacent structures,so as to determine the puncture path.The planned puncture path is able to effectively avoid the pancreas blood vessels,colon,spleen,kidney,gallbladder and so on.CT/MRI guided biopsy need to select the largest layer of the lesion.Puncture 16G coaxial puncture needle to the edge of the lesion by the scheduled puncture path with the planned puncture direction,angle and depth guided with imaging method,and adjustthe biopsy needle timely,then insert 18G biopsy needle removing 1 to 2 tissues.Check whether the sample is adequate or not,and if the sample size is insufficient,then puncture again to obtain enough tissues.Analysis of the observed indicators:take the pathology results of the surgery,and follow-up more than 12 months of imaging and/or clinical course as the final diagnostic reference,and record true positive or false positive,true negative or false negative.Calculate the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy of histopathological results diagnosed by biopsy guided by CT and MRI.Statistical indicators:data collection and statistical analysis using SPSS software 22.0.The classification data are expressed in terms of frequency and percentage,and data are compared by chi-square test or Fisher exact test.Continuous data are described as mean ± standard deviation(X±S)and they were comparede with two samples t test,or Wilcoxon rank sum test.P<0.05 for the results was significantly different.Results73 patients completed CT/MRI guided pancreatic biopsy operation,and the success rate of biopsy is 100%.MRI guided puncture path mostly reached the pancreas lesion through the organ space,and reduced the damage to adjacent organs.Compared with the CT guidance,the difference was significant(?2=25.130,P=0.001).Puncture time of MRI guidance is longer than that of CT guidance,which were(31.2±4.38)min and(25.5±5.85)min respectively,and the difference between the two groups was statistically significant(t=8.882,P=0.001).All patients had no major complication,and 8 cases(10.96%)had secondary complications.The incidence of complications guided by MRI was lower than that by CT,but there was no significant difference between the two groups(?2=4.444,P=0.108).Percutaneous needle biopsy histopathology and final diagnosis:73 patients received a clear histopathology diagnosis,and the total clinical success rate is 100%.Biopsy of 25 cases of malignant histopathological results were guided by MRI(80.65%,25/31),6 cases were benign or non-tumor(19.35%,6/31).27 cases were finally diagnosed with pancreatic cancer,and 4 cases were diagnosed with benign lesions.Malignant tumor were 34 cases with biopsy pathological by CT-guided(88.10%,37/42),5 cases of benign tumor or non-tumor(11.9%,5/42).41 cases were finally diagnosed with pancreatic cancer,and1 case was diagnosed with benign lesion.Diagnostic ability of CT/MRI-guided biopsy:the accuracy of biopsy by CT and MRI-guided were 90.48%(38/42)[95%CI,77.4%-97.3%]and 93.55%(29/31)[95%CI,78.6%-99.2%]respectively,but there was no significant difference in the diagnostic accuracy between the two methods(?2=0.223,P=0.637).The sensitivity,specificity,PPV and NPV of MRI-guided biopsy were 92.59%(25/27)[95%CI,75.7%-99.1%],100%(4/4),100%(25/25),66.67%(4/6)respectively.And were 90.24%(37/41)[95%CI,76.9%-97.3%],100%(1/1),100%(37/37),20%(1/5)by CT-guided biopsy respectively.There was no significant difference in the diagnostic sensitivity between the two methods(?2=0.112,P=0.738).Conclusion1.Percutaneous pancreatic biopsy guided by MRI and CT can fully obtain diagnosed samples with low complication rate.they are both minimally invasive,safe and effective way to guide the biopsy.2.MRI guidance has the advantages of accuratelocation of the suspicious pancreatic lesion area,accurate guidance of the biopsy of the site,which is expected to be higher than that of CT guidance in the diagnosis accuracy and sensitivity,which is potentially more safe and effective means for percutaneous pancreatic biopsy.3.The advantages of vascular flow effect and arbitrary azimuth imaging with MRI are helpful to choose shorterpuncture pathway by dorsal,gastrointestinal and other organs gapto reach the target lesion,which is conducive to reduce the incidence of complications.Part IIClinical Evaluation of CT-guided Iodine 125 Particle Interstitial Brachytherapy Combined with Intraarterial Infusion Chemotherapy in the Treatment of Advanced Pancreatic CancerIntroductionRadical resection is the preferred treatment for pancreatic cancer,and multidisciplinary treatment such as radiotherapy and chemotherapy is the main palliative treatmentof locally advanced and metastatic pancreatic cancer.The unique biological characteristics of pancreatic cancer is rich in connective tissueand poor in tumor vascular perfusion,so it is insensitive to most chemotherapeutic agents.The regional intraarterial infusion chemotherapy(RIAC)of pancreatic cancer increases the drug concentration at the lesion and avoids systemic toxicity at the same time,which has been safely used to inhibit tumor growth and reducethe incidence of liver metastasesmore effectively.There is no clear consensus on the optimal treatment of locally advanced pancreatic cancer.The dose of the target of the pancreatic tumor when the external beam radiation therapy(EBRT)irradiation is done will adversely affect the organs around the pancreas.125I interstitial radiation therapy can cause the greatest damage within the tumor tissue,and radiation dose of the surrounding healthy tissue drop sharply and impair light.Compared with EBRT,it can improve the local control rate of tumor and improve the survival rate.For patients with pancreatic cancer who occur liver metastases,transarterial chemoembolization(TACE)combined with 125I particles implantationcan also achieve good results.At present,the biggest problem of the technology is the accuracy of radioactive particle implantation with the guidance intraoperativeis not high enough,and the spatial distribution of particles and the preoperative treatment plan is still a big error,which directly affects the therapeutic effect.Intravascular interventional therapy as the center of the individual comprehensive treatment model enhance the safety and effectiveness of local treatment of tumor.ObjectiveIn this study,we retrospectively analyzed the clinical efficacy of advanced pancreatic cancer(APC)patients treated with 125I particle interstitial brachytherapy by CT-guided combined with RIAC,and compare the clinical efficacy with only RIAC,then analyze objective response rate(ORR),clinical benefit rate(CBR),progression-free survival rate(PFS),overall survival(OS),pain relief and postoperative complications of different treatment methods of progressive pancreatic cancer.Materials and MethodsRetrospective analyze data of patients with complete follow-up record who were diagnosed with advanced pancreatic cancer from January 2012 to July 2016 in Anhui Provincial Hospital.Fifty patients with 125I particle interstitial brachytherapy by CT three-dimensional accurate guidedwere enrolled in this study.The tumor stage ?were 27 cases,and stage IV were 23 cases.These patients were then treated with RIAC treatment,and they received 125I particle implantation 1 to 3 times and RIAC 1 to 6 times.The control group selected 43 patients treated with RIAC alone,the tumor stage ? were 21 cases,and stage ? were 22 cases,and they received RIAC 1?6 times,and the interval time was 3?4 weeks.There were no significant difference in age,sex,lesion size,tumor stage and whether or not distant metastasis between the two groups.Criteria for selected cases:(1)All cases were preoperatively diagnosed with pancreatic cancer by pathology in surgery or biopsy;(2)According to the Union for InternationalCancer Control(UICC)2002 staging standards,select stage ? and stage?panceatic cancer patients who were without indication of surgical resection;(3)Karnofsky Performance Status(KPS)? 60 points,or physical status ECOG(Eastern Cooperative Oncology Group)score<2 points;(4)expected survival period>3 months.Criteria for exclusive cases:(1)severe coagulation dysfunction(international standard ratio INR>1.5 or activated partial thromboplastin time twice or more than the normal time or platelet count<50000 cells/cubic millimeter);(2)tumor diameter>7 cm;(3)severe cardiopulmonary dysfunction;(4)patients with advanced cachexia;(5)refused to sign informed consent.According to preoperative CT and MRI enhanced scan images,transmitt them to the treatment planning system(TPS),and carefully outlined the gross tumor volume(GTV),planned target volume(PTV)and surrounding vital organs.Calculate the needle path and depth,the number of needles and the number of particles.Particle activity was(2.2?2.6)×107 Bq.Set prescription dose(PD)110?140 Gy,D90>90%PD,V100>90%,V200<50%.CT-guided 125I particle implantation:According to the TPS and the scope of the lesion,select and determine the most appropriate particle implantation puncture level and puncture path to ensure that the three-dimensional particle distribution commensurate with the extent of lesions.Adjust the needlecon firmed by incontinuos CT scan,implant the 18G particleneedle to the edge of the lesion.Gradually retract the particles implantneedle from deep to shallow interval 5?15 mm and implanted a 125I radioactive particles each time,and keep the adjacent particles the same in distance.Ensure that the number of implanted particles and TPS treatment plan error<10%.Particle implantation quality control measures:CT scan was performed immediately after particle implantationto confirm the location and number of implanted particles.Particle supplementation implantation or other treatment measures were done if necessary.Assessment parameters:prescription dose of target volume(v)percentage,including V100,V200,and so on,the target volume ratio(D),including D100,D90;Treatment volume rratio(TVR).Evaluation Reference:Target dose D90>MPD,suggesting good implant quality.MPD should be PD.The Conformation index is the ratio of the target volume of PD to the total target volume.Particle implantation dose uniformity<20%PD;DVH shows the absorbed dose measured of the normal tissue of adjacent structures.RIAC operation of pancreatic cancer:all patients had been completed the abdomen CT enhance scanbefore the puncture,and clear the exact location of the lesion in the pancreas and whether liver metastasis or not.According to the different location of the lesion of the pancreas,put the catheter super-selectively into the duodenal artery(pancreatic cancer),splenic artery(pancreatic tail cancer)and superior mesenteric artery(pancreatic head cancer)respectively.Infuse chemotherapy drugs in the feeding artery of the corresponding lesion of the tumor respectively:gemcitabine 1000 mg/m2,oxaliplatin 100 mg/m2.The interval between the two treatments was 3-4 weeks.TACE of liver metastases:when there was a liver metastases,half of the total amount of chemotherapeutic drugs were used in the hepatic arterial infusion.After the completion of the above-mentioned perfusion chemotherapy,intube the super-selective catheterinto the hepatic arterial line by DSA angiography,and clear the location,size,number and the rich blood supply of the liver metastases,and 1/3 of the total amount of the chemotherapy drug oxaliplatin with iodized oil 5?10 ml were emulsified into lipiodol suspension emulsion,and 150?350 ?m PVA particles to embolize tumor arterial trunk if needed.The two treatment interval is the same as RIAC.Follow-up:Abdomen CT enhance scan was taken 1,2,6 and 12 months after the operation to determine the change of the size of the pancreatic tumor and liver metastasis,and review whether the new metastasis occourred.Clinical hematological examinationincluding CA19-9,blood,blood biochemistry,coagulation and other tests were done.The visual analog scale(VAS)was used to assess pain relief in patients before and after the operation.Record details of the symptoms,complications or adverse events of all patients within 2 months after the operation.Determine curative effect:According to the evaluation criteria of WHO solid tumor efficacy(RECIST 1.1)judge the efficiancy.Analyze the objective response rate(ORR)and clinical benefit rate(CBR)of them.The main indicator identified in this study was the overall survival(OS),and the secondary indicator of the study was Progression-Free Survival(PFS).Statistical analysis of indicators:Data collection and statistical analysis analyzed using SPSS software 22.0.The classification data are expressed in terms of frequency and percentage.Com pare them by ?2 test or Fisher exact test.Continuous data are described as mean ± standard deviation(X±S),compare them by two samples t testor Wilcoxon rank sum test.Using Kaplan-Meier to analyze and mapsurvival curves to estimate the survival rate,and the survival curves were compared by log-rank test.P<0.05 was considered to be statistically significant.ResultsFifty patients underwent 125I particles implantation 54 times,and the success rate was 100%.1 case received 125I particles implantation 3 times,and 2 cases received 2 times.Set prescription dose(PD)110?140 Gy,average D90 is 128 Gy.Percentage of prescription dose of D100 reached the target area is>95%PD,D90>90%PD,Percentage of target volume covered 100%of prescription dose>90%(V100>90%),V200<50%.No abdominal infection,intestinal fistula,pancreatic fistula and other serious adverse reactions occurred,4 cases occurred particle shift found immediately CT scan after the operation.Two groups of patients successfully completed the corresponding treatment interventions,and they were followed up for 12 to 54 months,and the efficacy evaluation was completed.The ORR and CBR of 125I particle implantation combined with RIAC and RIAC alone were compared between the two groups.According to the tumor stage hierarchical comparison,the ORR of all the patients,stage ? patients and stage ?patients 2 months and 6 months after the operation were 62.0%,88.9%,30.4%and 61.4%,80.0%,31.6%respectively,and the CBR of them was 76%,96.3%,52.2%and 77.3%,92.0%,52.6%respectively.The ORR of all RIAC patients,stage? patients and stage ?patients 2 months and 6 months after the operation were 39.5%,47.6%,31.8%and 36.7%,46.7%,26.7%respectively,and the CBR of them was 53.5%,61.9%,45.5%and 46.7%,60.0%,33.3%respectively.The clinical efficacy of 125I paticle implantation combined with RIAC of patients with advanced and stage ? pancreatic cancer was higher than that of RIAC alone(P<0.05),but there was no significant difference between the two groups in stage ? pancreatic cancer patients(P>0.05).The PFS of all the patients,stage ? patients and stage ? patients were 8.7,8.8 and 4.4 months respectively in 125i paticle implantation combined with RIAC.The PFS of all the RIAC patients,stage ? patients and stage ? patients were 5.2,5.7 and 3.2 months respectively.The PFS of the particle implantation group is higher than the control group,and the difference was statistically significant(P<0.05).The median survival time of particle implantation group was significantly prolonged in clinical follow-up.Compared with the control group,the median survival time was 13.2 and 8.7 months.The survival rates of 1,2,3 years were 56.2%,28.0%,8.0%and 37.2%,11.6%,2.3%respectively.Analyze stage ? patients alone,the median survival time were 15.9 and 8.9 months in the two groups,and the 1,2,3 years survival rate is 66.7%,37.0%,11.1%and 38.1%,14.3%,4.8%respectively.The OS of the whole group of particle implantation group including stage ? patients was significantly longer than that of the control group,and the difference of survival trend was statistically significant(P<0.05).However,the median survival time of stage ?pancreatic cancer patients was 9.5 and 8.3 months,and the 1,2,3 years survival rate were 43.5%,17.4%,4.3%and 36.4%,9.1%,0%respectively.There was no significant difference in the survival trend between the two groups(P>0.05).Through CT three-dimensional reconstruction and TPS to make treatment plan,accurately puncture implanted particles by CT-guided,which can make sure that D90>90%PD,V100>90%,V200<50%.Abdominal pain are varying degrees of ease after particle implantation in patients.Regardless of the stage ? or ? patients with advanced pancreatic cancer,VAS scores were significantly decreased in 1 months after implantation,and the pain relief was significantly lower than that in the control group(P = 0.001).Conclusion1.For patients of 125I particle interstitial brachytherapy in the treatment of advanced pancreatic cancer by CT-guided combined with RIAC,the ORR and CBR of 2 months and 6 months after the operation were superior to that of RIAC alone.2.For patients of 125I particle interstitial brachytherapy in the treatment of advanced pancreatic cancer by CT-guided combined with RIAC,the PFS and OS were significantly higher than that of RIAC alone,and stage III patients benefit more.For the patients of stage ?,the postoperative PFS was prolonged and the pain symptoms were significantly relieved,which could greatly improve the quality of life.3.125I particle interstitial brachytherapy in the treatment of advanced pancreatic cancer by CT-guided combined with RIAC is safe and effective,which can achieve better local control rate,and improve the quality of life of patients.It is one of the powerful comprehensive treatment for the advanced pancreatic cancer patients.