Initiative on Superselective Conventional Transarterial Chemoembolization Results (INSPIRE).

Several publications show that superselective conventional TransArterial ChemoEmbolization (cTACE), meaning cTACE performed selectively with a microcatheter positioned as close as possible to the tumor, improves outcomes, maximizing the anti-tumoral effect and minimizing the collateral damages of the surrounding liver parenchyma. Recent recommendations coming from the European Association for the Study of the Liver (EASL) and European Society of Medical Oncology (ESMO) highlighted that TACE must be used in Hepatocellular Carcinoma (HCC) "selectively targetable" and "accessible to supraselective catheterization." The goal of the manuscript is to better define such population and to standardize superselective cTACE (ss-cTACE) technique. An expert panel with extensive clinical-procedural experience in TACE, have come together in a virtual meeting to generate recommendations and express their consensus. Experts recommend that anytime cTACE is proposed, it should be ss-cTACE, preferably with a 1.5-2.0 Fr microcatheter. Ideally, ss-cTACE should be proposed to patients with less than five lesions and a maximum number of two segments involved, with largest tumor smaller than 5 cm. Angio Cone-Beam Computed Tomography (CBCT) should be used to detect enhancing tumors, tumor feeders and guide tumor targeting. Whole tumor volume should be covered to obtain the best response. Adding peritumoral margins is encouraged but not mandatory. The treatment should involve a water-in-oil emulsion, whose quality is assessable with the "drop test." Additional particulate embolization should be systematically performed, as per definition of cTACE procedure. Non-contrast CBCT or Multi-Detector Computed Tomography (MDCT) combined with angiography has been considered the gold standard for imaging during TACE, and should be used to assess tumor coverage during the procedure. Experts convene that superselectivity decreases incidence of adverse effects and improves tolerance. Experts recommend contrast-enhanced Computed Tomography (CT) as initial imaging on first follow-up after ss-cTACE, and Magnetic Resonance Imaging (MRI) if remaining tumor viability cannot be confidently assessed on CT. If no response is obtained after two ss-cTACE sessions within six months, patient must be considered unsuitable for TACE and proposed for alternative therapy. Patients are best served by multidisciplinary decision-making, and Interventional Radiologists should take an active role in patient selection, treatment allocation, and post-procedural care.

Ultraselective conventional transarterial chemoembolization: When and how?

Ultraselective conventional transarterial chemoembolization (cTACE), defined as cTACE at the most distal portion of the subsubsegmental hepatic artery, is mainly performed for hepatocellular carcinoma (HCC) ≤5 cm. Distal advancement of a microcatheter enables injection of a larger volume of iodized oil into the portal vein in the limited area under non-physiological hemodynamics. As a result, the reversed portal flow into the tumor through the drainage route of the tumor that occurs when the hepatic artery is embolized is temporarily blocked. By adding gelatin sponge slurry embolization, both the hepatic artery and portal vein are embolized and not only complete necrosis of the tumor but also massive peritumoral necrosis can be achieved. Ultraselective cTACE can cure small HCCs including less hypervascular tumor portions and replace surgical resection and radiofrequency ablation in selected patients.

Superselective Conventional Transarterial Chemoembolization for Hepatocellular Carcinoma: Rationale, Technique, and Outcome.

Conventional transarterial chemoembolization with ethiodized oil and gelatin sponge (GS) particles is a standard technique for hepatocellular carcinoma. Ethiodized oil can temporarily block tumor sinusoids, portal venules, hepatic sinusoids, and arterial microcommunications. By adding GS embolization, strong ischemic effects not only on the tumor but also on the surrounding liver parenchyma can be achieved. Superselective conventional transarterial chemoembolization is mainly indicated for patients with Child-Pugh scores of 5-8, tumors ≤ 7 cm, and ≤ 5 lesions. According to a Japanese nationwide survey, the 5-year survival rate of patients with Child-Pugh class A and a single tumor was 52%.

Development of Conventional Transarterial Chemoembolization for Hepatocellular Carcinomas in Japan: Historical, Strategic, and Technical Review.

OBJECTIVE: This article reviews the development of transarterial chemoembolization (TACE) in Japan, particularly ethiodized oil-based conventional TACE, from historical, strategic, and technical points of view. We also present the current status of standardized conventional TACE. CONCLUSION: Conventional TACE has been developed toward a more-selective and hemodynamic-conscious method, along with technical innovation and knowledge accumulation. Standardization of this method is necessary for further scientific evaluation.

Transarterial chemoembolization failure/refractoriness: JSH-LCSGJ criteria 2014 update.

In the 2010 version of the Japan Society of Hepatology (JSH) consensus-based treatment algorithm for the management of hepatocellular carcinoma (HCC), transarterial chemoembolization (TACE) failure/refractoriness was defined assuming the use of superselective lipiodol TACE, which has been widely used worldwide and particularly in Japan, and areas with lipiodol deposition were considered to be necrotic. However, this concept is not well accepted internationally. Furthermore, following the approval of microspheres, an embolic material that does not use lipiodol, in February 2014 in Japan, the phrase 'lipiodol deposition' needed to be changed to 'necrotic lesion or viable lesion'. Accordingly, the respective section in the JSH guidelines was revised to define TACE failure as an insufficient response after ≥2 consecutive TACE procedures that is evident on response evaluation computed tomography or magnetic resonance imaging after 1-3 months, even after chemotherapeutic agents have been changed and/or the feeding artery has been reanalyzed. In addition, the appearance of a higher number of lesions in the liver than that recorded at the previous TACE procedure (other than the nodule being treated) was added to the definition of TACE failure/refractoriness. Following the discussion of other issues concerning the continuous elevation of tumor markers, vascular invasion, and extrahepatic spread, descriptions similar to those in the previous version were approved. The revision of these TACE failure definitions was approved by over 85% of HCC experts.

Hepatic arterial embolization for unresectable hepatocellular carcinomas: do technical factors affect prognosis?

PURPOSE: To evaluate retrospectively whether technical factors of hepatic arterial embolization affect the prognosis of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Inclusion criteria of this study were the following: (1) patients received embolization as the initial treatment during 2003-2004, (2) Child A or B liver profile, (3) five or fewer HCCs with maximum diameter of 7 cm or smaller, and (4) no extrahepatic metastasis. Patient data were gathered from 43 centers. Prognostic factors were evaluated using univariate and multivariate analyses. RESULTS: Eight hundred fifteen patients were enrolled. The 1-, 3-, 5-, and 7-year overall survival rates were 92.0 % (95 % CI 90.1-93.9), 62.9 % (95 % CI 59.3-66.6), 39.0 % (95 % CI 35.1-43.0), and 26.7 % (95 % CI 22.6-30.8) in all patients. Univariate analysis showed a Child-Pugh class-A, alpha-fetoprotein level lower than 100 ng/ml, tumor size of 3 cm or smaller, tumor number of 3 or fewer, one-lobe tumor distribution, nodular tumor type, within the Milan criteria, stage I or II, no portal venous invasion, use of iodized oil, and selective embolization were significantly better prognostic factors. In the multivariate Cox model, the benefit to survival of selective embolization remained significant (hazard ratio 0.68; 95 % CI 0.48-0.97; p = 0.033). CONCLUSION: Selective embolization contributes to survival in patients with HCCs.

Arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery in patients with recurrent hepatocellular carcinoma after chemoembolization.

PURPOSE: To evaluate the arterial blood supply to the caudate lobe of the liver from the proximal branches of the right inferior phrenic artery (RIPA) in patients with recurrent hepatocellular carcinoma after transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Thirteen patients, including 10 who had a history of TACE of the caudate artery (A1), underwent TACE of the proximal RIPA branches. Iodized oil distribution was evaluated by computed tomography (CT) 1-week after TACE. Angiographic findings were also evaluated. RESULTS: Previously embolized A1 was occluded (n = 15) or attenuated (n = 2). In one of three patients without A1 TACE, A1 was also attenuated. TACE was performed at the first branch of the proximal RIPA (n = 8), the first branch of the anterior branch (n = 6), and the first branch of the posterior branch (n = 1), respectively. Iodized oil was mainly distributed into the dorsal part of the Siegel lobe (SP) (n = 10), the caudate process (n = 1), and both (n = 2). In three of seven patients who had undergone serial RIPA angiography, RIPA parasitization to SP was suspected before A1 TACE. CONCLUSION: The proximal RIPA branches mainly supply the SP when A1 is attenuated.

Efficacy of cone-beam computed tomography during transcatheter arterial chemoembolization for hepatocellular carcinoma.

Cone-beam computed tomography (CBCT) using a flat-panel detector is an alternative method of obtaining cross-sectional images. This technique is now being used during transcatheter arterial chemoembolization (TACE) for inoperable hepatocellular carcinoma (HCC). Several CBCT techniques are performed to detect HCC lesions: CBCT during portography (CBCTAP), CBCT during hepatic arteriography (CBCTHA), CBCT after iodized oil injection (LipCBCT), CBCT during arteriography (CBCTA) of extrahepatic collaterals. Almost all HCC lesions can be detected using these CBCT images. Three-dimensional arteriography using maximum intensity projection from CBCTHA images can identify the tumor-feeding branch. In particular, this technique is useful when the tumor stain cannot be demonstrated on arteriography. In addition, dual-phase CBCTHA can improve the diagnostic accuracy for hypervascular HCCs because corona enhancement can be detected around the tumor. To monitor the embolized area during TACE, selective CBCTHA or LipCBCT at the embolization point is useful. Two sequential CBCT scans without and with contrast material injection is also useful to confirm each embolized area of two vessels. Furthermore, CBCTA can prevent nontarget embolization. Although the image quality of CBCT is low compared to that of conventional CT, CBCT provides useful information that helps perform TACE for HCCs safely and effectively.

Angiographic evaluation of feeding arteries of hepatocellular carcinoma in the caudate lobe of the liver.

PURPOSE: To evaluate the origins of feeders of hepatocellular carcinoma (HCC) in the caudate lobe (S1). MATERIALS AND METHODS: Eighty-eight HCCs (mean diameter 21.4 mm) were treated by chemoembolization. The tumor-feeding caudate artery was confirmed when a tumor stain was demonstrated on angiogram and iodized oil was accumulated into the HCC and S1 on computed tomography (CT). The origins were divided into R(1) (right proximal), R(2) (right distal), L(1) (left proximal), L(2) (left distal), A (anterior segmental), P (posterior segmental), M (middle hepatic or medial segmental), Ph (proper hepatic), Ch (common hepatic), and Ex (extrahepatic). The origins of feeders supplying HCCs in the Spiegel lobe (SP; n = 36), the paracaval portion (PC; n = 38), and the caudate process (CP; n = 14) were also analyzed. RESULTS: One hundred sixteen feeders were identified: 11 (9.5%) arose from R(1); 21 (18.1%) arose from R(2); nine arose (0.9%) from L(1); 15 (12.9%) arose from L(2); 24 (20.7%) arose from A; 25 (21.6%) arose from P; seven (6.0%) arose from M; one (0.9%) arose from Ph; and three (2.6%) arose from Ex. HCCs in the SP and the PC were fed by feeders from both hepatic arteries (the ratios of right to left were 3:2 and 3:1, respectively), and HCCs in the CP were dominantly fed by feeders from the right hepatic artery. CONCLUSION: The caudate artery most frequently arises from the right hepatic artery, followed with almost equal frequency by the left hepatic, the anterior segmental, and the posterior segmental artery. The origins of the caudate arteries differ according to the subsegmental locations.

Ultraselective transcatheter arterial chemoembolization with a 2-f tip microcatheter for small hepatocellular carcinomas: relationship between local tumor recurrence and visualization of the portal vein with iodized oil.

PURPOSE: To retrospectively evaluate the relationship between local tumor recurrence and iodized oil deposition in the portal vein by using ultraselective transcatheter arterial chemoembolization (TACE) for small hepatocellular carcinoma. MATERIALS AND METHODS: One-hundred twenty-three tumors smaller than 5 cm in diameter (mean diameter, 1.9 cm; median diameter, 1.6 cm) were treated with TACE by using a 2-F tip microcatheter at a distal portion of the subsegmental artery of the liver. Portal vein visualization at spot radiography during TACE was divided into three grades, as follows: 0 = not visualized, 1 = limited near the tumor, and 2 = whole or extended to the embolized area. Local recurrence rates of each grade group were compared. The recurrent pattern was divided into intratumoral and peritumoral recurrence. Complications were also analyzed. RESULTS: Of the 123 tumors, 53 (43.1%) were classified as grade 2, 52 (42.3%) were classified as grade 1, and 18 (14.6%) tumors were classified as grade 0. Overall local recurrence rates at 12, 24, and 36 months were 25.6%, 34.7%, and 34.7%, respectively. The local recurrence rates for the grades 2, 1, and 0 groups were 7.9%, 24.8%, and 85.7%, respectively, at 12 months and 17.7%, 38.9%, and 85.7% at 24 months. Recurrence rates in the grade 2 group were significantly lower than those in the grades 1 and 0 groups (P = .0485 and P < .0001, respectively). Intratumoral recurrence was observed in 21 tumors, most of which were in the grade 0 group. Peritumoral recurrence was noted in 16 tumors, most of which were in the grade 2 group. There were no major complications. CONCLUSION: Ultraselective TACE was safe and effective in a significant number of tumors. In particular, local recurrence was significantly lower when a greater degree of portal vein visualization was demonstrated during TACE.

Extrahepatic blood supply to hepatocellular carcinoma: angiographic demonstration and transcatheter arterial chemoembolization.

PURPOSE: To evaluate the incidence of each extrahepatic collateral pathway to hepatocellular carcinoma (HCC) and to assess technical success rates and complications of transcatheter arterial chemoembolization (TACE) through each collateral. METHODS: We retrospective evaluated extrahepatic collateral pathways to HCC on angiography in 386 procedures on 181 consecutive patients. One hundred and seventy patients had previously undergone TACE. TACE through extrahepatic collaterals using iodized oil and gelatin sponge particles was performed when a catheter was advanced into the tumor-feeding branch to avoid nontarget embolization. RESULTS: A single collateral was revealed in 275 TACE procedures, two were revealed in 74, and three or more were revealed in 34. Incidences of collateral source to HCC were 83% from the right inferior phrenic artery (IPA), 24% from the cystic artery, 13% from the omental artery, 12% from the right renal capsular artery (RCA) and left IPA, 8% from the right internal mammary artery (IMA) and right intercostal artery (ICA), and 7% from the right inferior adrenal artery (IAA). Technical success rates of TACE were 53% in the right ICA, 70% in the cystic artery, 74% in the omental artery, 93% in the left IPA, 96% in the right IPA, and 100% in the right RCA, right IMA, and right IAA. Complications included skin necrosis after TACE through the right IMA (n = 1), cholecystitis after TACE through the cystic artery (n = 1), and ulcer formation after TACE through the right gastric artery (n = 1), in addition to pleural effusion and basal atelectasis after TACE through the IPA and IMA. CONCLUSION: Our study suggests that TACE through extrahepatic collaterals is possible with high success rates, and is also relatively safe.

Arterial blood supply to the posterior aspect of segment IV of the liver from the caudate branch: demonstration at CT after iodized oil injection.

PURPOSE: To retrospectively evaluate the arterial blood supply to the posterior aspect of segment IV of the liver with computed tomography (CT) after transcatheter arterial chemoembolization (TACE) with iodized oil through the caudate arterial branch of the liver for treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and patient informed consent were not required for this retrospective study. Twenty-four patients (11 men and 13 women; mean age, 68 years) with HCC originating in the caudate lobe (n = 23) or posterior aspect of segment IV (n = 1) were selected. TACE of the caudate arterial branch was performed in all patients, including one patient with HCC in the posterior aspect of segment IV who underwent TACE of the caudate arterial branch after CT helped confirm that iodized oil was not distributed in the tumor after TACE of the medial segmental artery. The distribution of iodized oil in the posterior aspect of segment IV was analyzed with CT 1 week after TACE. The number and origin of all arteries supplying the caudate lobe and the number of arteries embolized were determined. RESULTS: Thirty-three caudate arterial branches were embolized. Twenty-nine branches were derived from the right hepatic artery and four were derived from the left hepatic artery. A single branch was seen in 17 patients, two branches were seen in five, and three branches were seen in two. Eight patients simultaneously underwent additional TACE of branches of the right hepatic artery (n = 6) or right inferior phrenic artery (n = 2). At CT, iodized oil was seen to be distributed entirely (n = 19) or partially (n = 5) in the caudate lobe. Distribution of iodized oil at the posterior aspect of segment IV was observed in 16 patients (67%), including 13 (54%) whose caudate arterial branches were derived entirely from the right hepatic artery. CONCLUSION: The results of this study suggest that the caudate arterial branch, which is mainly derived from the right hepatic artery, frequently supplies the posterior aspect of segment IV. This knowledge is important for managing HCC in the posterior aspect of segment IV by means of TACE.

Combined use of an occlusion balloon catheter and a microcatheter for embolization of the unselectable right inferior phrenic artery supplying hepatocellular carcinoma.

We report the combined use of an occlusion balloon catheter and a microcatheter for transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC) fed by the unselectable right inferior phrenic artery (IPA). In one case, HCC was fed by the reconstructed right IPA via a small branch arising from the proximate portion of the celiac artery. In another, the tumor was fed by the right IPA that had been previously embolized with coils. TAE was successfully performed through a microcatheter placed in the celiac artery immediately proximal to the occluding balloon catheter of the celiac trunk and coil embolization of the left gastric artery.