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Objective:To study the safety and treatment outcomes of portal vein embolization (PVE) combined with lenvatinib plus an anti-programmed death-1(PD-1) antibody to treat patients with initially unreasectable hepatocellular carcinoma (uHCC).Methods:This study retrospectively analyzed the data of six patients with uHCC who received first-line combined systemic therapy with lenvatinib plus an anti-PD-1 antibody, and then underwent pre-hepatectomy PVE at the Department of Liver Surgery at Zhongshan Hospital, Fudan University from May 2019 to November 2020. All enrolled patients were males, aged (54.6±6.2) (ranged 46 to 63) years. Tumor response and liver volume were evaluated by medical imagings once every 2 months (±2 weeks) and evaluated using the Response Evaluation Criteria in Solid Tumours (version 1.1). Patients were followed-up by outpatient interviews or by phone calls to record their survival and tumor outcome status.Results:Three of the six enrolled patients had Barcelona Clinic Liver Cancer stage A and three had stage B disease. One patient achieved a partial response and five patients had stable diseases. The mean ± s. d. future liver remnant (FLR) percentage was (29.0±8.9) % before PVE and the combination therapy, and was (41.3±10.8) % before the last evaluation for liver surgery ( t=10.79, P<0.001). Hepatectomy was carried out in five patients, and one patient who failed to develop significant FLR hypertrophy did not undergo hepatectomy. Grade B post-hepatectomy liver failure and major postoperative complications (i.e. pleural effusion requiring additional percutaneous drainage) occurred in one patient. After a median post-operative follow-up of 4.5 (range: 1.0-12.3) months, all five patients were alive and were tumor free. Conclusion:PVE followed by hepatectomy is feasible in a uHCC patients receiving systemic therapy with lenvatinib and an anti-PD-1 antibody.
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Objective To evaluate the safety and efficacy of brachytherapy with 125I seed strand in treating implanted main portal vein tumor thrombus (MPVTT) in experimental rabbits.Methods VX2 tumor cell line was implanted in the main portal vein (MPV) of 32 New Zealand white rabbits to establish MPVTT models.The rabbits were randomly divided into the treatment group (group T,n=16) and the control group (group C,n=16).125I seed strand was implanted in the MPVTT of the rabbits of group T,while blank seed strand was implanted in the MPVTT of the rabbits of group C.After the implantation,the changes in general condition,body weight and laboratory testing results were recorded.Two weeks after the treatment,every 8 rabbits from each group were sacrificed,and the specimens were collected and sent for pathological examination.The remaining rabbits were fed till they died,and then autopsy was conducted.Multi-slice spiral CT manifestations,histopathological findings,Ki-67 labeling index and apoptosis index were used to assess the curative effect,and the results were compared between the two groups.Results At each observation time point after brachytherapy,the weight loss of the experimental rabbits was more obvious in group C than in group T.No statistically significant differences in liver functions and white blood cell count existed between the two groups (P＞0.05).The mean MPVTT volume of group T and group C were (565.40±220.90) mm3 and (2 269.90±437.00) mm3 respectively (P＜0.001);the Ki-67 labeling indexes were (4.14±1.84)％ and (33.82± 6.07)％ respectively (P=0.001);the median survival days were (39.50±2.37) d and (27.38±1.22) d respectively (P=0.001).Conclusion For the treatment of implanted MPVTT in experimental rabbits,brachytherapy with 125I seed strand is safe and effective.
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Objective To evaluate the influence of thermal damage on the cell proliferation,invasive metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma (HCC) through experiments in vitro,and to explore the relationship between thermal ablation and the recurrence,metastasis of HCC.Methods The McA-RH7777 HCC cell thermal damage model was established by using external heating method.The effect of thermal damage on the proliferation of HCC cells was detected by Kit-8 assay (CCK-8),and the cell cycle changes were studied by flow cytometry.The effect of thermal damage on the invasion potential of HCC cells was assessed by using Transwell assay.Fluorescence quantitative polymerase chain reaction (RT-PCR) and Western blot were used to evaluate the influence of thermal damage on HCC cell invasion potential,and on the mRNA and protein expression levels of EMT-related molecular markers,including VEGF,MMP-9,Nm23,E-cadherinand vimentin.Results Heating treatment of McA-RH7777HCC cells was performed by putting the cells in 43.5℃ water basin for 30 min.Two to five days after heating treatment the cell proliferative ability was significantly higher than that of control group (P＜0.05).At 48-72hours after heating treatment the proportion of HCC cells in G1 phase was obviously reduced and the proportion of HCC cells in S+G2 phase was significantly increased,the differences were statistically significant (P＜0.05).Compared with the control group,the difference in HCC cell invasion potential determined at 24 h after heating treatment was not significant,while the HCC cell invasion potential determined at 72 h after heating treatment was strikingly increased (22.3±2.46 vs.14.2±l.82,P＜0.001).Real-time PCR and Western blotting results indicated that at 72 h after heating treatment the expression levels of VEGF,MMP-9 and vimentin were significantly increased,while the expression level of E-cadherin was remarkably decreased,the differences were statistically significant (P＜0.05).Conclusion Thermal damage with sub-lethal heating dose can induce McA-RH7777 HCC cell to develop epithelial-mesenchymal transition and to enhance its proliferation and invasive metastasis potential,and HCC cells show higher malignant potential.
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Objective To evaluated the clinical significance of embolization of arterio-portal venous shunt (APVS) in hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) treated by transcatheter arterial chemoembolization (TACE) and portal vein stenting. Methods Twenty-six HCC patients with MPVTT and marked APVS, who were treated with TACE and portal vein stenting, were enrolled in this study. Portal vein stenting was performed via percutaneous transhepatic approach, which was followed by the embolization of the feeding arteries of APVS by using suitable embolic agents. The portal vein pressure levels were separately measured before, after portal vein stenting and after APVS embolization. The results were statistically analyzed. Results Both the portal vein stenting and APVS embolization were successfully accomplished in all the 26 patients. Hepatic angiography and portal venography performed before portal vein stenting revealed bidirectional portal flow in 16 cases and hepatofugal portal flow in 10 cases. Among the 16 patients with bidirectional portal flow, remarkable improvement of portal vein to liver blood flow after portal vein stenting was seen in 14, and obvious recovery of main portal vein to liver blood flow after APVS embolization in 2. Obvious recovery of main portal vein to liver blood flow after APVS embolization was also demonstrated in 10 cases with hepatofugal portal flow. The portal vein pressure determined before, after portal vein stenting and after APVS embolization was (50.1±6.3) cmH2O,(43.5± 7.5) cmH2O and (36.9 ±8.2) cmH2O respectively. After portal vein stenting the portal vein pressure was significantly decreased when compared with the preoperative pressure, and the difference was statistically significant (P<0.05); after APVS embolization the portal vein pressure was further decreased (P<0.05). Conclusion For HCC patients with MPVTT and marked APVS, portal vein stenting can effectively restore the portal blood flow and reduce the portal vein pressure; and embolization of APVS can further reduce the pressure of portal vein, thus the bidirectional portal flow or hepatofugal portal flow will return to normal hepatopetal flow.
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Objective To investigate the curative effect of transcatheter arterial chemoembolization (TACE) combined with endovascular 125I seed strip implantation for the treatment of primary hepatocellular carcinoma (PHC) complicated by extensive portal vein tumor thrombus. Methods The clinical data of 72 patients with PHC complicated by extensive portal vein tumor thrombus were retrospectively analyzed. The patients were divided into group A (n=32) and group B (n=40). TACE combined with endovascular 125I seed strip implantation was performed for the patients of group A, while only TACE was employed for the patients of group B. The changes of portal vein tumor thrombus, the survival time and procedure-related adverse events were recorded. The preoperative and postoperative measured values were compared using paired samples t test, the count data were evaluated by χ2 test, and the survival time was analyzed with Kaplan-Meier method. Results Technical success rate of portal vein 125I seed strip implantation was 100%. No serious procedure-related adverse events occurred. The median survival periods of group A and group B were 210 days and 141 days respectively, the difference between the two groups was statistically significant (P=0.012). Conclusion For the treatment of primary hepatocellular carcinoma complicated by extensive portal vein tumor thrombus, TACE combined with endovascular 125I seed strip implantation can significantly improve the patient’s survival time.
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Objective To establish a stable animal model of implanted main portal vein tumor thrombus (MPVTT) in rabbits and to evaluate its usefulness in research so as to provide the basis for clinical treatment. Methods Twenty-four New Zealand white rabbits were randomly divided into group A (control group,n=10) and group B (study group,n=14). For the rabbits of the study group, a sac-like pouch was sewed up in the anterior wall of the main portal vein, and then the tumor slice was injected into the portal vein through the pouch and it was hung and fixed on the inner wall of the main portal vein with the help of the reserved suture. For the rabbits of the control group, only a sac-like pouch was sewed up in the anterior wall of the main portal vein after opening the abdomen. After the treatment, the animals were kept under observation on the general condition, body weight and survival time. Postoperative multi-slice spiral CT scan was performed once a week to check the growth of portal vein tumor thrombus and the metastasis. The experimental rabbits were separately sacrificed for pathologic examination, the volume of MPVTT was determined and the metastasis was evaluated. The survival time of the remaining rabbits were analyzed. Results The tumor formation rate of the study group was 100%. The mean body weight of the rabbits of the study group (No.9-No.14 rabbits) and the control group at 35 days after the procedure was (1.48±0.19) kg and (2.08 ±0.17) kg respectively. The mean survival time of the study group (No.9-No.14 rabbits) was (41.7 ±4.72) days. Multi-slice spiral CT scan revealed MPVTT, metastasis and collateral circulation due to portal vein obstruction. Pathological examination confirmed the presence of thrombus in the portal vein and metastasis . Conclusion Stable MPVTT in animal models that can be used for imaging evaluation are successfully established. This study proves that multi-slice spiral CT scan is of great value in diagnosing and monitoring the growth of MPVTT and metastasis, which provides useful basis for clinical research and treatment of MPVTT.
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Objective To discuss the technical skill of super-selective catheterization for “one-way valve occlusion” of the common hepatic artery during transcatheter arterial chemoembolization (TACE). Methods A total of 128 patients with “one-way valve occlusion”of the common hepatic artery were enrolled in this study, who were admitted to authors’ department to receive TACE during the period from 2000 to 2011. The lesions included hepatocellular carcinoma (n = 110), cholangiocellular carcinoma (n = 3) and hepatic metastasis (n=15). “One-way valve occlusion”of the common hepatic artery occurred in 90 patients (70.3%, 90/128) after 2-5 times of TACE had been carried out, and in the other 38 patients (29.7%, 39/128) the “one- way valve occlusion” of the common hepatic artery was recognized at the initial TACE procedure. Super-selective hepatic catheterization was performed via the superior mesenteric artery (SMA) approach or celiac artery (CA) approach using coaxial micro-catheter catheterization technique. The success rate and fluoroscopy time of super-selective catheterization were recorded, and the results were compared between the two approaches. Results A total of 337 times of hepatic super-selection catheterization were performed in 128 patients, with a mean of 2.6 times for each case. The success rate was 100%. Of the 337 procedures, the catheterization was via CA approach in 148 (43.9%, 148/337) and via SMA approach in 189 (56.1%, 189/337). The mean fluoroscopy time in CA approach group was 3.2 minutes(ranged 1-6 minutes), and in SMA group was 15.3 minutes(ranged 5-40 minutes). The difference between the two groups was statistically significant (P < 0.05). Conclusion Super- selective hepatic catheterization for “one-way valve occlusion” of the common hepatic artery can be achieved through SMA approach or CA approach by using coaxial micro-catheter catheterization. Compared with SMA approach, the technique of hepatic catheterization through CA approach is much simpler and the fluoroscopy time is significantly shorter.
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ObjectiveTo establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT)and examine its growth with MDCT and 3D-MPR. MethodsTumor cell line VX2 was inoculated subcutaneously into rabbit to develop the primary tumor, which was then cut into small strips. Purse-string suture was performed on the anterior wall of IVC after the laparotomy in eighteen New Zealand white rabbits.The tumor strip was injected into IVC through the purse and suspensory fixed on the inner wall of IVC. The general conditions,body weight,and the survival time were monitored after operations.MDCT examinations were performed with plain scan,arterial phase,portal phase and venous phase enhancement every week for all animals and 3D-MPR were acquired.The volumes of IVCTT were calculated.IVC,IVCTT and metastasis were examined with gross and histological pathology. ResultsThe IVCTT was confirmed by MDCT and 3D-MPR images.Collateral varicose veins caused by IVC obstruction and metastasis were also shown in images.IVCTT and metastasis were confirmed by pathological method. The success rate of IVCTT was 100 ％. The mean survival time of operated animals was(49.5±4.4)days. ConclusionsInjecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish the IVCTT animal model. MDCT and 3D-MPR are valuable methods to monitor the growth and metastasis of IVCTT in animal models. The model of implanted IVCTT of rabbits provides a useful tool for the research of treatment of IVCTT.
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ObjectiveTo study the risk factors of renal artery pseudoaneurysm (RAP) following partial nephrectomy.MethodsOpen partial nephrectomy was performed on a total of 464 cases of renal cell cancer from July 2003 to May 2010. Five patients ( 1.1％ ) had postoperative hemorrhage from RAP.The surgery technique of the open partial nephrectomy, the clinical presentation, imaging findings and treatment of RAP were reviewed. The anatomical characteristics of these five renal tumors on enhanced CT were quantified using the R.E.N.A.L. Nephrometry Score System.ResultsAll five cases were male, two had tumors on the left side and three on the right side. Median tumor size was 3.6 cm ( range from 2.5 to 5 cm; Radius score 1 - 2). Four tumors were exophytic of these, three had a major endophytic component (≥50％) deep in the parenchyma (Exophytic/endophytic score 2 ), one was entirely endophytic (score 3 ). The distance of all the tumors to the collecting system was ≤4 mm ( Nearness score 3 ). Four of the five tumors were across the polar line and/or renal axial midline ( Location score 3 ). The other tumor was located under the lower pole ( Location score 1 ) but close to the renal hilar. All patients presented with delayed gross haematuria and decreasing hemoglobin occurred on mean postoperative day 12 (3 -23 day). Four patients complained of flank pain, two of which had signs of hypovolemia requiring blood transfusion. The diagnosis was confirmed by the contrast medium-enhanced CT and selective angiography, and RAP was found most commonly arising from the segmental branch of renal artery. Superselective microcoil angioembolization was successfully performed in four cases, once in three cases and twice in the remaining case. The procedure failed in one patient and a nephrectomy was done. At a mean follow-up of 21 months (12 -30) , all patients had normal renal function without evidence of recurrence.ConclusionsRAP should be considered in all patients who had delayed hematuria after partial nephrectomy. A central, deep tumor and its relationship to the segmental branch of renal artery could be an important risk factor for this complication. Choosing the case properly for partial nephrectomy and suturing the transected vessels and the defect of parenchymal correctly could reduce occurrence of this serious complication. Early use of selective angioembolization could be a primary choice of treatment.
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Objective To report the preliminary results of placing metallic stent and ~(125)Ⅰ seed strand combined with transcatheter arterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) with inferior vena cava (IVC) obstruction. Methods From March 2009 to June 2009, implantation of radioactive ~(125)Ⅰ seed strand and metallic stent combined with TACE treatment was performed in 8 cases of HCC with malignant IVC obstruction. All patients were males with a mean age of (60.6 ± 9.6) years, ~(125)Ⅰ seed strand and Z-type soft-expandable metallic stent were placed in the obstructive segment of IVC, which was followed by TACE. Before and after the treatment, the diameter of the obstructive segment of IVC, the pressure gradient between right atrium and distal end of obstructive segment of IVC, and the symptoms related to the obstruction were estimated and recorded, the results were compared individually. Clinical follow-up was conducted in all patients. Results A total of 8 stents and 10 ~(125)Ⅰ seed strands were placed in the obstructive segment of IVC. Altogether 138 ~(125)Ⅰ seeds were implanted in 8 patients. Obvious clinical improvements were obtained after therapy. No complications occurred in all patients except one patient who experienced acute renal dysfunction at the second day after therapy. During a mean of (2.1 ± 0.6) months follow-up, occlusion of IVC stent was detected in 1 patient. The remaining stents remained patent. Conclusion Our initial results indicate that placement of ~(125)Ⅰ seed strand and metallic stent combined with TACE is a safe and feasible therapeutic option for advanced HCC with malignant IVC obstruction.
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Percutaneous transhepatic biliary drainage(PTBD) is an effective therapeutic option for obstructive jaundice.With various novel puncture instruments being created,the manipulating technique being improved and medical idea being updated,PTBD has been widely employed in clinical practice for alleviating the biliary tract obstruction.In order to standardize this technique this paper aims to make some suggestions for the PTBD guidelines concerning the indications,contraindications,operative skill,postoperative management,complications and their preventions,points for attention,etc.
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Objective To report the preliminary results of placing metallic stent and 125I seed strand combined with transcatheter arterial chemoembolization(TACE) for the treatment of hepatocellular carcinoma(HCC) with inferior vena cava(IVC) obstruction.Methods From March 2009 to June 2009,implantation of radioactive 125I seed strand and metallic stent combined with TACE treatment was performed in 8 cases of HCC with malignant IVC obstruction.All patients were males with a mean age of(60.6 ? 9.6) years.125I seed strand and Z-type self-expandable metallic stent were placed in the obstructive segment of IVC,which was followed by TACE.Before and after the treatment,the diameter of the obstructive segment of IVC,the pressure gradient between right atrium and distal end of obstructive segment of IVC,and the symptoms related to the obstruction were estimated and recorded,the results were compared individually.Clinical follow-up was conducted in all patients.Results A total of 8 stents and 10 125I seed strands were placed in the obstructive segment of IVC.Altogether 138 125I seeds were implanted in 8 patients.Obvious clinical improvements were obtained after therapy.No complications occurred in all patients except one patient who experienced acute renal dysfunction at the second day after therapy.During a mean of(2.1 ? 0.6) months follow-up,occlusion of IVC stent was detected in 1 patient.The remaining stents remained patent.Conclusion Our initial results indicate that placement of 125I seed strand and metallic stent combined with TACE is a safe and feasible therapeutic option for advanced HCC with malignant IVC obstruction.
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Objective To retrospectively analyze the mid-term clinical results of direct intrahepatic portosystemic shunt (DIPS) in treating patients with portal hypertension. Methods DIPS were created in 23 patients with portal hypertension. Both preoperative and postoperative portal systemic pressure gradient (PPG), liver function and clinical symptoms were recorded and compared. Shunt patency was checked by color Doppler ultrasonography and the data were statistically analyzed by Kaplan-Meier method. Results DIPS creation was successfully accomplished in all 23 patients. No serious complications occurred after DIPS except for hemorrhagic ascites (n = 1) and mild hepatic encephalopathy (n = 3). Mean PPG significantly decreased from preoperative (32.6 ? 5.3) mmHg with a range of (23 - 43) mmHg to postoperative (10.1 ? 2.7) mmHg with a range of (5-14) mmHg (P
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Objective To evaluate the hemocompatibility of domestic silicone-covered stent in the iliac arteries of canine model. Methods Eighteen domestic stents were placed in ililac arteries of 9 adult dogs after larger ballon PTA, which included 10 silicone-covered stents and 8 bare stents for control. DSA was performed at 1,4,12 weeks after stent implantation in the iliac arteries of two groups to observe the outcomes of patency or restenosis. Animals were then euthanized isolating and stainning the stented arteries with hematoxylin and eosin for histological examination. Finally, the acute thrombosis, reendothelialization and the neointimal proliferation of both covered and bare stents were quantified on histological cross-section. Results All bare stents were patent in 12 weeks, but two silicone-covered stents were occluded at 4,12 week respectively (patent rate was 80%). Stented vascular stenosis rate was averaging 72.3% at 12 week in covered stents and 36.7% in bare stents. Conclusions The hemocompatibility of silicone-covered stents is not better than that of bare stents. Silicone appear to be inert in this experimental application.