Pilot study of transcatheter arterial ethanol embolization under closed renal circuit for large renal cell carcinomas

Clinical research priorities in renal cell carcinoma: renal cell carcinoma chemoprevention strategies including target populations, proposed agents, and clinical trial designs--Workgroup No. 6. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC).

Renal cell carcinoma (RCC) is the most common form of kidney cancer. Immunotherapy with interferon-α (IFNα) and interleukin-2 (IL-2) has been the historical therapy of choice for the treatment of locally advanced or metastatic RCC prior to the more recent development of targeted therapies, including sunitinib and bevacizumab (combined with IFNα). Clinically and statistically significant advantages have been shown with both sunitinib and the combination of bevacizumab + IFNα versus IFNα alone in the treatment of advanced or metastatic RCC. The present study evaluated the incremental costs of bevacizumab + IFNα versus sunitinib for the first-line treatment of advanced or metastatic RCC assuming similar efficacy for these treatments. The efficacy profiles of bevacizumab + IFNα or sunitinib alone have been shown (indirectly) to be similar in patients with RCC; indeed, median progression-free survival (PFS) with either treatment is in the 10- to 11-month range. Therefore, a cost-minimization analysis was performed, focusing on direct medical costs only (drugs, administration and management of adverse events). The analysis considered the perspective of the Italian National Health Service (NHS), comparing the cost of bevacizumab (10 mg/kg) plus IFNα (9, 6 or 3 million IU [MIU]) versus sunitinib (50 mg) as first-line therapies for advanced or metastatic clear-cell RCC. The average cost per treated patient (year 2010 values) was assessed for the two treatment options at 11 months (median PFS). Assuming a PFS of 11 months for both treatment options, bevacizumab + IFNα (9 MIU) would be a lower cost strategy (cost savings of €2052 per patient) than sunitinib. This difference arises mainly from the reduction in the acquisition cost of bevacizumab to the NHS (risk-sharing agreement). The cost advantages for bevacizumab would increase in parallel with a reduction in IFNα dosing; for example, with IFNα 6 MIU the corresponding cost savings would be €4185, and with 3 MIU the cost advantage would be €6320 per patient. This analysis suggests that bevacizumab + IFNα is a cost-saving alternative to sunitinib in the treatment of first-line metastatic RCC. Its superior safety profile also meant that the cost of managing adverse events was lower for bevacizumab + IFNα than for sunitinib.

Transcatheter arterial embolization (TAE) is used for the treatment of patients with malignant liver tumors. However, the proangiogenesis effect of TAE-associated hypoxia has not been adequately studied. The goal of this study was to determine angiogenic activity in tumors subjected to TAE by evaluating the tumor microvessel density (MVD). Mammary cancer 13762 NF tumor cells were inoculated into the livers of male Sprague-Dawley rats. TAE was performed 12-14 days after tumor inoculation. Rats were divided into 4 groups on the basis of treatment type. Control group animals (n = 16) were subjected to sham TAE without polyvinyl alcohol (PVA) particles. Animals in the other 3 groups were subjected to TAE with 1 (n = 11), 2 (n = 8), or 3 (n = 10) mg of PVA particles. Rats were killed 3-6 hours or 2 or 3 days after embolization, and the liver tumor tissues were dissected and frozen in liquid nitrogen. Tumor tissue slides were prepared, stained with CD-31, and evaluated for MVD. Blood samples collected just before sacrificing the animals were used to measure serum vascular endothelial growth factor (VEGF) levels. Tumors treated with TAE showed varying degrees of central necrosis with residual viable tumor cells in the periphery. Tumor MVD in animals treated with TAE was significantly higher than that in the control group (23.6 versus 17.5; P = 0.001). Although the MVD in animals treated with TAE using 1 mg of PVA was higher than that in the control group, this difference was not statistically significant. TAE using 2 mg of PVA resulted in a significant increase in tumor MVD (25.9 versus 17.5; P = 0.007). Use of 3 mg of PVA did not result in any further increase in MVD. There was a significant increase in tumor MVD in the animals killed 2 or 3 days after TAE compared with the control group (24.5 versus 17.5; P = 0.002). The animals treated with TAE showed a statistically significant increase in VEGF levels compared with the control group. TAE of hepatic tumors results in the stimulation of angiogenesis in the residual viable tumor, which could have an adverse effect on the therapeutic efficacy of TAE.

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Transcatheter arterial embolization has been used as a therapeutic maneuver for lower gastrointestinal bleeding. The availability of highly selective arteriography has made this procedure safer and warrants re-evaluation. A retrospective chart review was done of all patients undergoing arteriography for presumed lower gastrointestinal bleeding at two acute-care community hospitals. Causes of bleeding, clinical outcome, and complications caused by transcatheter arterial embolization were recorded. There were 26 arteriographically identified bleeding sites in the colon and small bowel. The most frequent cause of bleeding was diverticulosis (12 patients), with the diagnosis being arterio venous malformation in two, and one unknown colonic source. Transcatheter arterial embolization was attempted for 17 separate bleeding episodes in 16 patients. Transfusion requirements were an average (+/- standard deviation) of 7 +/- 1.43 units per patient. Transcatheter arterial embolization was successful in stopping bleeding in 14 cases (82 percent). Two patients had surgery after transcatheter arterial embolization: one for colonic necrosis and one for persisting bleeding. There were two more unsuccessful procedures; one had a successful repeated transcatheter arterial embolization, and one stopped spontaneously. One patient rebled during the same hospitalization and was controlled with intra-arterial vasopressin. There were two deaths, both secondary to sepsis unrelated to the transcatheter arterial embolization or the gastrointestinal tract. Transcatheter arterial embolization is a relatively safe and successful procedure in patients with massive lower gastrointestinal hemorrhage. It is an excellent choice of therapy for patients that are poor candidates for surgery, but its role in other patients remains to be defined.

To evaluate the possibility of selective hyperthermia following transcatheter arterial embolization (TAE) with ferucarbotran using a newly developed inductive heating (IH) device. Twelve Japanese white rabbits were separated into four groups: those treated with TAE using a mixture of ferucarbotran and lipiodol (F-L group); those treated with ferucarbotran and gelatin sponge powder; those treated with saline and lipiodol; and a control group. These four groups received IH. Nine rabbits with renal VX2 carcinoma were separated into three groups: IH after TAE (IH-TAE tumor), TAE without IH (TAE tumor), and no treatment (control tumor). The temperature of the tumor was kept at 45 degrees C for 20 min. The therapeutic effect was pathologically evaluated by TUNEL staining. In the heating rates of the kidney, the F-L group showed significantly greater values than the group in which iron was not used. In the IH-TAE tumor group, tumors could be selectively heated. In TUNEL staining, the IH-TAE tumor and TAE tumor groups showed significantly greater values of apoptosis rate than in the control tumor group. IH following TAE with a mixture of ferucarbotran and lipiodol was capable of inducing selective hyperthermia with our device. However, further investigation is needed to confirm its safety and effectiveness in the treatment of malignant neoplasms in humans.

Objective To compare the clinical efficacy of laparoscopic radical nephrectomy for large renal cell carcinoma (＞7 cm) between retroperitoneal approach and transperitoneal approach.Methods From Jan 2008 to Dec 2013,the data of 68 patients who underwent laparoscopic radical nephrectomy for large renal tumor(＞7 cm) in our hospital were reviewed.There were 41 male patients and 27 female patients,whose age ranged from 43 to 73 (mean 58.4t6.9) years old.The size of tumor was between 7.0 to 12.5 cm (mean 8.9± 1.1 cm).Left renal tumor was found in 37 patients and right renal tumor in 31 patients.Clinical stages of the tumors were T2 to T3.All patients were undergone the laparoscopic radical nephrectomy,including retroperitoneal approach in 42 cases (observation group)and transperitoneal approach in 26 cases (control group).The exclusive criteria included inferior vena cava tumor thrombus,lymphatic or distant metastasis,previous operation history in the same region,multiple tumors.There were no significant differences in the age,gender,tumor size and location within two groups (P＞0.05).The perioperative indexes and oncological outcomes,such as operation time,blood loss,incidence of blood transfusion,incidence of SIRS,postoperative hospital stay,complications and follow-up results,were collected and compared between two groups.Results Conversion occurred in two cases from observation group and one case from control group.Operative time in observation group was significantly shorter than that in control group (114.9±24.4 min vs.131.2±29.9 min,P＜0.05).Bowel function recovered more rapidly in observation group than in control group (1.7±0.6 d vs.2.2±0.6 d,P＜0.05).However,the estimated blood loss,the incidence of blood transfusion,the postoperative hospital stay,the incidence of SIRS and perioperative complications showed similar results in the 2 groups (P＞0.05).The histopathological examination confirmed renal cell carcinoma in all cases.Observation group included 35 pT2 stage and 7 pT3a stage cases,while control group consisted of 21 pT2 stageand 5 pT3a stage cases.The follow-up duration ranged from 4 to 38 months (mean 17 months).Mean overall survival were 17.1 months in observation group and 18.7 months in control group.Progression free survival time was 15.7 months in observation group and 17.1 months in control group.Cox survival analysis showed that only pre-operative stage of the tumor were independent risk factor for the survival time (P=0.018) and progression free survival time (P=0.020),while the operative approach was not the independent risk factor (P=0.298,0.314).Conclusions For large renal tumors (＞7 cm),laparoscopic radical nephrectomy was safe and feasible.Compared to the transperitoneal approach,retroperitoneal approach cost less operative time and faster bowel recovery.But the operation approach is not an independent risk factor for the survival time and progression free survival time. Key words: Renal cell carcinoma; Laparoscopy ; Retroperitoneal

Recently, transcatheter arterial embolization (TAE) has been used to treat hepatocellular carcinoma (HCC), yet much is still unknown regarding its optimal use. Eighty-four patients with HCC after TAE underwent surgical resection. Fifty of the tumors were less than 3 cm (small HCC [S-HCC]), and 34 were 3 cm or larger (large HCC [L-HCC]). Necrosis rate, distribution of residual HCC, histopathology of the main tumor, and proliferating activity of residual HCC by means of proliferative cell nuclear antigen (PCNA) were examined. Twenty-two randomly selected patients with HCC treated with standard chemotherapy were used as non-TAE control subjects. A necrosis rate of greater than 95% was seen in 35 cases of S-HCC and in 15 of L-HCC. All five nonencapsulated tumors were L-HCC and had a much lower necrosis rate. No tumors in the control group showed a necrosis rate of greater than 95%. Encapsulated tumors were categorized according to their tumor interiors, capsules, and extracapsular zones. Complete necrosis of the tumor interior was 80.0% and 35.3% in S-HCC and L-HCC, respectively. Viable residual tumors were found mainly in the extracapsular zone in S-HCC, whereas in L-HCC they were located primarily in the tumor interior. Most capsules were affected by tumor necrosis and the subsequent healing process, resulting in a thick secondary capsule. Tumor interior necrosis was uniform and coagulative in S-HCC, in contrast to L-HCC, in which necrotic regions comprised several necrosis units of differing texture and were divided by fibrous septa. In contrast, the control group revealed spotty, sparse necrosis. Non-TAE tumor capsules were thin and pathologically characteristic of those naturally occurring in tumors, as opposed to the thick fibrous capsules, which are inducible by TAE therapy. In the TAE group, the PCNA positivity rates were 37.5%, 52.5%, and 100% in Grades 1, 2, and 3/4 combined, respectively. At the tumor-nontumor boundary of the extracapsular region, PCNA-positive cells were detected in 55.0% of the cases. The thickened tumor capsule serves as a good postoperative indicator of TAE response. Small tumors seem to be affected in the tumor interior, whereas extracapsular invasion undermines the TAE effect. PCNA was helpful in detecting the tumor-nontumor boundary and useful as a parameter of viability of HCC after TAE.

Introduction We aimed to evaluate the effect of transcatheter arterial embolization (TAE) with iodized oil (Lipiodol) on temperature change during cryoablation (CA) for renal cell carcinoma (RCC). Material and methods We retrospectively reviewed patients receiving CA for RCC from February 2020 to July 2021, including those who received Lipiodol TAE prior to CA (TAE group) and those who underwent only CA with comparable clinical and tumor characteristics (non-TAE group). Clinical data and tumor characteristics of both groups were recorded. The temperature readings of each cryoprobe at every 15 s and ‘time to −100 °C’ were compared between the groups. Results A total of 17 patients with 18 RCCs were recruited (seven in the TAE group and 11 in the non-TAE group). The ‘time to −100 °C’ was significantly longer in the TAE group than in the non-TAE group (64.5 ± 24.3 s vs. 48.8 ± 9.7 s, p = 0.018). Positive correlation between ‘time to −100 °C’ and tumor maximal diameter, RENAL nephrometry and PADUA score were observed in the non-TAE group, while no corresponding correlation was found in the TAE group. Conclusions Pre-embolization with iodized oil influences the temporal temperature changes during cryoablation by disrupting the positive correlation between the time to reach the target temperature and tumor characteristics.

Ischemic cholangiopathy

Objective To evaluate the indications,method and prognosis of emergent hepateetomy and tran-scatheter arterial embolization(TAE) for spontaneous rupture of primary liver carcinoma(PLC). Methods Clinical data of 85 cases with PLC were analyzed. Patients were divided into four groups: the group of delayed hepatectomy (group A,n=30);the group of emergent transcatheter arterial embolization (group B,n=22);the group of emer-gent hepatectomy (group C, n=18) and the group of medical treatment (group D, n=15). The hemostasis achieve-ment ratio, operative complications, perioperative morbidity, 1-year and 3-year survival rates among the four groups were compared. Results In group A and B, celiac urteriogram in 52 cases showed that extravasation of contrast media happened in 14 cases (26.9%). The hemostasis achievement ratio was 100% (30/30, 22/22, 18/18) in group A,B and C,respectively,which was remarkably higher than that in group D(40%,6/15) (P<0.05);The in-hospital fatality was 0% (0/30),3.8% (2/52) and 16.7% (3/18),which was lower than that of group D(80.0%, 12/15) (P<0.01). The 1-year survival rate was 76.7% and 3-year survival rate of group A was 53.3%, which was higher than that of group B (45.5 % and 31.8 %) and group C (44.4% and 33.3 %) (P<0.05). The cases in group D did not survive one year(P<0.01). Conclusions Emergent hepatectomy and transcatheter arterial emboli-zation are safe and feasible for spontaneous rupture of primary hepatocellular carcinoma. For those with resectable ca-ses,surgical resection is the first choice after transcatheter arterial embolization. Key words: Hepatocellular carcinoma; Hepatectomy; Hepatic artery embolization; Spontaneous rupture

During the past 8 years we have treated 268 patients with primary hepatocellular carcinoma (HCC); total extirpation of the tumor was carried out in 138. Thirty-one of the patients with resectable HCCs had already been treated with transcatheter arterial embolization (TAE) of the liver before they were referred to us. The clinical values of preoperative TAE were retrospectively evaluated for those 31 patients and for the remaining 107 patients without TAE. There were no substantial differences between the two study groups in the clinical and histopathologic backgrounds. No differences were observed in the extent of liver resection, estimated blood loss during surgery, and operation time. During surgery, however, troublesome intra-abdominal complications relevant to TAE were encountered in 15 patients, and detection of tumors was impossible, even with intraoperative ultrasonography, in five patients in the group with TAE. Such findings were not present in any of the patients without TAE. Postoperative morbidity and mortality rates were similar in the two groups. There was no significant difference in the rate of recurrence of tumor in the liver, but the recurrence time was significantly shorter in the group with TAE. TAE did not improve the long-term survival rates in patients either with or without cirrhosis. Results of our study seem to indicate that preoperative TAE is meaningless in the treatment of resectable HCCs and therefore should be avoided, particularly in patients with advanced cirrhosis of the liver.

Background and aims: Colonoscopy is preferred for treatment of lower gastrointestinal bleeding (LGIB). However, several conditions such as poor bowel preparation can cause endoscopic failure, leading to surgery or transcatheter therapy as alternative options. We aimed to assess the efficacy and safety of transcatheter arterial embolization (TAE) for LGIB in patients with endoscopic failure.Methods: Between January 2005 and June 2015, 93 consecutive patients with acute LGIB underwent visceral angiography at three academic hospitals. Among them, a total of 52 patients were treated with TAE for LGIB and analyzed. Technical success, complications and 30-day rebleeding and mortality after TAE were investigated retrospectively in patients with and without localization of LGIB.Results: Technical success of TAE was achieved in all patients. After TAE, 30-day rebleeding and mortality rate were 27% (14/52) and 29% (15/52), respectively. TAE was performed without localizing bleeding site in 32 of 52 patients (62%). Between patients with and without localized bleeding site, there were no significant differences in 30-day rebleeding rate (25% vs. 28%) and mortality rate (15% vs. 38%). Causes of death were mostly unrelated to bleeding. Only two cases of bowel infarction occurred after TAE in patients without bleeding site localization. Rebleeding could be predicted if the patient received more than six units of packed red blood cell transfusion before TAE in multivariate analysis.Conclusions: TAE can be an effective treatment for LGIB even without localizing bleeding site.

Long-term Outcomes After Percutaneous Radiofrequency Ablation for Renal Cell Carcinoma

The aim of this study is to determine if selective transcatheter arterial embolization (TAE) of the branches of the internal iliac artery in patients with pelvic trauma is a risk for gluteal necrosis. Retrospective chart review. Civilian Level I trauma center. Twenty patients with pelvic fractures and hemorrhage. Selective and nonselective TAE of the internal iliac artery and its branches. The location of all fractures was identified as well as the fracture type. Selective TAE was also distinguished from nonselective TAE. Orthopaedic surgical intervention was recorded. Cases of gluteal necrosis and wound infection were recorded as well as renal failure and anaphylactic reaction to intravenous contrast. Of the 551 patients identified with pelvic fractures, 20 patients were identified to have undergone TAE from January 2004 to January 2009. Of these, 18 cases were treated with selective TAE and two with nonselective unilateral TAE. No complications of gluteal muscle or pelvic skin necrosis, wound infection, renal failure, or anaphylaxis were noted in any of these cases. Average patient age was 55 years with average Injury Severity Score 17. Eleven cases underwent orthopaedic surgical procedures, eight of which involved open reduction and internal fixation of the acetabulum or hemiarthroplasty of the hip. Selective TAE of internal iliac branches including the gluteal arterial branches appears to be safe in patients with pelvic and acetabular fractures with and without orthopaedic surgical treatment. Nonselective TAE of the internal iliac artery may also be safe when performed unilaterally. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.