Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial disease.

PURPOSE: This study was designed to assess the effect of calcium on the efficacy of DEB during revascularization of steno-obstructive SFA lesions. METHODS: Sixty patients with de novo lesions of the superficial femoral artery underwent endovascular treatment with drug eluting balloons (DEB). DEB was selected according to vessel reference diameter (1:1). In case of residual stenosis > 50 % or flow-limiting dissection, postdilatation with conventional balloon or provisional stenting was done. Patients were classified into eight groups according to circumferential distribution of calcium on CT-angiography axial images (from 0° to 360°) and to its length (length < or > 3 cm) evaluated with digital-subtraction-angiography. Ankle-brachial index (ABI), late lumen loss (LLL), target lesion revascularization (TLR), primary (PP) and secondary (SP) patency, major adverse events (MAE), and Rutherford shift were evaluated at 1-year follow-up and correlated with the amount of calcium. RESULTS: Revascularization was successful in all cases. Flow-limiting dissection occurred in five cases (8.3 %) with a higher circumferential degree of calcium and solved in three cases with postdilatation and in the other two with provisional stenting. DEB effect was lower in patients with higher degree of calcium (>270° vs. <90°): ABI 0.71 ± 0.07 versus 0.92 ± 0.07; LLL 0.75 ± 0.21 versus 0.45 ± 0.1; PP 50 versus 100 %; SP 50 versus 100 %; TLR 25 versus 0 %; MAE 25 versus 0 %. CONCLUSIONS: Calcium represents a barrier to optimal drug absorption. Circumferential distribution seems to be the most influencing factor with the worst effect noticed in 360° calcium presence.

The "DEBELLUM"--lower limb multilevel treatment with drug eluting balloon--randomized trial: 1-year results.

AIM: The aim of the present paper was to make a report of the 12-month clinical outcomes of the DEBELLUM (Drug-Eluting-Balloon-Evaluation-for-Lower-Limb- mUltilevel-treatMent) randomized trial. METHODS: From September 2010 to March 2011, 50 patients were randomized between drug eluting balloon (DEB, N.=25) and conventional angioplasty balloon (PTA, N.=25). Patients were symptomatic for claudication and critical limb ischemia, with de novo stenosis or occlusion in the femoropopliteal (SFA) and infrapopliteal (BTK) region. Only in the SFA primary stenting was allowed and postdilatation performed with DEB or PTA depending on the assigned group. RESULTS: One hundred and twenty-two lesions were treated: 92 (75.4%) SFA, 30 (24.6%) BTK. Twenty (40%) patients presented multilevel concomitant femoropopliteal and infra-popliteal lesions. Late lumen loss (LLL) was 0.64±0.9 mm in DEB group vs. 1.81±0.1 mm in the control group (P=0.01). In non-stented segment LLL was 0.63±0.9 mm (DEB) vs. 1.70±0.6 mm (PTA), P<0.01. In the stent subgroup was LLL 0.65±0.2 mm (DEB) vs. 1.91±0.3 mm (PTA), P<0.01. In the femoropopliteal region the overall LLL was 0.61±0.8 mm for DEB vs. 1.84±0.3 mm for PTA (P=0.02). BTK the overall LLL was 0.66±0.9 mm (DEB) vs. 1.69±0.5 mm (PTA) (P=0.03). The overall TLR was 12.2% for DEB and 35.3% for PTA (P<0.05). Amputation rate was 4% (DEB) vs. 12% (PTA), P=0.36. Thrombosis was 4% (DEB) vs. 8% (PTA), P≥0.05. Major adverse events 24% (DEB) vs. 60% (PTA), P<0.05. ABI improved more in the DEB group: 0.81±0.3 vs. 0.68±0.13 (P=0.02). Fontaine stage increased (from II b to I) 80% DEB vs. 56% PTA (P<0.05). CONCLUSION: Results confirm and reinforce initial 6-month outcomes. In.Pact DEB balloons can be considered efficient to reduce restenosis rate.

Low-dose contrast-enhanced time-resolved MR angiography at 3T: diagnostic accuracy for treatment planning and follow-up of vascular malformations.

AIM: To assess the accuracy of low-dose contrast-enhanced time-resolved 3T magnetic resonance angiography (MRA) for the morphological and functional assessment of vascular malformations (VM), and to evaluate its diagnostic potential for the depiction of treatment-induced changes. MATERIALS AND METHODS: Twenty-five patients with known VM underwent MRA to evaluate the location and extent of lesions and their haemodynamic characteristics. Three-dimensional (3D) T1-weighted time-resolved sequences were acquired following the administration of 0.05mmol/kg of gadobenate dimeglumine. VM were classified according to their morphology and haemodynamic characteristics. All patients thereafter underwent conventional angiography to confirm the diagnosis and to treat the lesions (embolization or sclerotherapy). Follow-up MRA was performed 30 days after treatment to assess morphological and functional changes. A visual analogue scale (VAS) was used to clinically assess the severity of symptoms before and after therapy. RESULTS: Based on haemodynamic characteristics, VM were classified as predominantly arterial [4 (16%)], artero-venous [19 (76%)] or venous [2 (8%)]. Twenty-three (92%) lesions were classified as high-flow VM and two (8%) as low-flow VM. Intralesional thrombosis was present in 17 (68%) lesions before therapy and in 10 lesions (40%) after therapy. The median VAS scores were 5±1 before treatment and 4±2 after treatment. Very good correlation (Spearman's correlation coefficient: rho=0.87; p=0.000) was noted between the reduction of lesion size on follow-up MRA and pain relief as assessed by VAS. CONCLUSION: Low-dose contrast-enhanced time-resolved 3T MRA can be used to define morphological and functional aspects of VM accurately during treatment planning and follow-up, and can identify post-therapy changes that positively correlate with treatment outcome.

Chlamydophila pneumoniae infection in patients undergoing carotid artery stent.

Although several reports have correlated Chlamydophila pneumoniae (CP) infection with carotid endarterectomy and coronary stent, no data have been reported on the potential relationship between this pathogen and carotid artery stenting (CAS). Hence, we evaluated 47 subjects, 27 symptomatic and 20 asymptomatic, before CAS intervention and during the follow up, for the presence of CP DNA and anti-CP antibodies, including chlamydial HSP60 (Cp-HSP60). Before stent placement, CP DNA was detected exclusively in symptomatic patients, all of whom were also positive for CP IgG and IgA and 85.7 percent of them also had CP-HSP60 antibodies. At the follow-up, all CP DNA positive and 11 out of the 13 symptomatic patients with Cp-HSP60 antibodies became negatives. In contrast, no change was observed for CP- IgA antibodies. Despite the small number of patients, the present study advocates an important role of CP infection in symptomatic patients with carotid artery disease. Our findings also suggest that stent placement and/or therapy might have a role in favouring resolution of inflammation, though not affecting persistence of CP infection.

Nonsurgical treatment of staple line leaks after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is gaining popularity as a "per se" bariatric procedure due to its effectiveness on weight loss and comorbidity resolution. The most feared and life-threatening complication after LSG is the staple line leak and its management is still a debated issue. Aim of this paper is to analyze the incidence of leak and the treatment solutions adopted in a consecutive series of 200 LSG. METHODS: From October 2002 to November 2008, 200 patients underwent LSG. Nineteen patients (9.5%) had a body mass index (BMI) of >60 kg/m(2). A 48-Fr bougie is used to obtain an 80-120-ml gastric pouch. An oversewing running suture to reinforce the staple line was performed in the last 100 cases. The technique adopted to reinforce the staple line is a running suture taken through and through the complete stomach wall. RESULTS: Staple line leaks occurred in six patients (mean BMI 52.5; mean age 41.6 years). Leak presentation was early in three cases (first, second, and third postoperative (PO) day), late in the remaining three cases (11th, 22nd, and 30th PO day). The most common leak location was at the esophagogastric junction (five cases). Mortality was nihil. Nonoperative management (total parenteral nutrition, proton pump inhibitor, and antibiotics) was adopted in all cases. Percutaneous abdominal drainage was placed in five patients. In one case, a small fistula was successfully treated by endoscopic injection of fibrin glue only. Self-expandable covered stent was used in three cases. Complete healing of leaks was obtained in all patients (mean healing time 71 days). CONCLUSION: Nonoperative treatment (percutaneous drainage, endoscopy, stent) is feasible, safe, and effective for staple line leaks in patients undergoing LSG; furthermore, it may avoid more mutilating procedures such as total gastrectomy.

Chronic abdominal pain associated with intermittent compression of the celiac artery.

Recurrent abdominal pain (RAP), surely one of the most frequent causes of medical intervention, is frequently present in many gastrointestinal disease. Usually no structural and/or biochemical alterations can be demonstrated. This condition is, therefore, considered to be due to functional disorders such as irritable bowel syndrome (IBS) or functional dyspepsia. Previous observations suggest the presence of a rare alteration of celiac vessels among the possible causes of RAP. This pathological condition was known as Dunbar syndrome. We report 2 cases of chronic abdominal pain. The former reported weight loss and the latter anemia with iron deficiency. It is remarkable that patients with initial diagnosis of IBS can be affected by celiac disease (CD), which is the cause of their abdominal pain. Our patients were tested for CD; the former was negative and IBS was diagnosed, the latter was positive and a gluten free diet was prescribed. The presence of an epigastric bruit, accentuated during expiration, suggested a possible vascular alteration known as tripod celiac artery compression syndrome. Duplex Doppler sonography suggests the diagnosis of celiac arterial constriction due the diaphragmatic ligament. These cases show that tripod celiac artery compression syndrome might be a cause of RAP and that it may be evaluated and investigated when the clinical examination discloses an abdominal systolic bruit.

Stent graft in TIPS: technical and procedural aspects.

Transjugular intrahepatic portosystemic shunt (TIPS) is a nonoperative therapeutic option for the management of portal hypertension, variceal bleeding, recurrent ascites, Budd-Chiari syndrome. In view of the many issues surrounding the use of TIPS, in 1994 the US National Digestive Diseases Advisory Board convened a scientific conference to review the current data available and to establish the indications and controindications for this procedure. However there are still unsolved problems especially short primary patency of the shunt due to intimal hyperplasia, which causes a reduction of the shunt lumen thus favoring a return of the portal hypertension with recurrent variceal bleeding. Several study were performed in the last years to evaluate the efficacy of covered stent in order to reduce shunt disfunction secondary to intimal hyperplasia. PTFE seems to be more efficient in the prevention of restenoses. In our experience more then 100 patients were treated with the Viatorr stent-graft. After a follow-up ranging from 1 to 50 months we reported a 1- year primary patency rate of 83.8%. However the use of the stentgraft is correlate with a high rate of hepatic hencefalopathy (46.6 %). In case of hepatic hencefalopathy refractory to the conventional medical therapy, TIPS reduction should be performed.

Interventional radiology techniques in the treatment of complications due to videolaparoscopic cholecystectomy.

INTRODUCTION: The development of videolaparoscopic cholecystectomy (VLC) has represented an important achievement in the search for minimally invasive surgical procedures, and especially in the surgical management of such a common and costly disease as cholelithiasis. However, the literature shows that, while VLC carries a similar mortality rate to open surgery, it has a greater incidence (2-5 times) of iatrogenic injury to the biliary tract and hepatic hilum [3, 5, 10, 25, 28]; this incidence further increases in cases of so-called "hard cholecystis" [10, 13, 25, 28, 30]. An equally minimally invasive technique is therefore needed to treat these lesions; this technique should be effective and safe, allow for shorter hospital stays and lower costs, and be made available at all the centres where VLC is performed. MATERIAL AND METHODS: We evaluated 60 patients (28 women and 22 men, age range 41-71) with 24 peritoneal collections (14 bilomas, 10 abscesses), 35 biliary stenosis (clips, chronic-developing lesions), and 2 vascular lesions as direct iatrogenic post-LC injuries. The most frequent clinical symptoms were jaundice, pain, sepsis, abdominal distension, and abdominal colic due to retained common bile duct stones. We carried out 60 percutaneous biliary reconstruction procedures, 44 biliary drainages (4 internal, 4 external), 6 combined radiological-endoscopic approaches with the Rendez-Vous technique, and 2 embolisations. RESULTS: All procedures had 100% technical success; the biliary reconstruction procedures had a 2% morbidity rate (sepsis, cholangitis). The clinical emergencies (choleperitoneum, haemoperitoneum, severe jaundice) resolved in 72 hours for 55 of the 60 patients (92%). The combined percutaneous-endoscopic procedures with the biliary Rendez-Vous technique were successfully performed in 5 out of 6 cases, allowing reconstruction of bile duct continuity and remission of symptoms, without the need to resort to surgical anastomosis. At a recent follow-up of the patients who had been managed only percutaneously, one showed patency of the bile ducts and had the stent removed after 18 months, and two showed optimal functioning of the stent that was still in place after 5 and 8 months respectively; two patients were lost to follow-up. Primary biliary patency at 60 months from biliary reconstruction was 75%. Maximum and immediate dilatation was obtained at the first attempt in most cases. Reoperation was avoided in 59 out of 60 patients. Only one patient with full transection of the common bile duct was reoperated on after insertion of a biliary drainage catheter. The overall length of hospital stays was between 1 and 4 weeks. CONCLUSIONS: Interventional radiology carried out according to indications seems to be the most natural way to treat the complications of VLC. It spares the patients, who opted for a minimally invasive technique like VLC, the need to undergo open surgery, and allows for shorter hospital stays and more efficient cost management for the hospital.

[Use of a trans-brachial access during percutaneous treatment of abdominal aortic aneurysms]. / Utilitàdi un accesso trans-brachiale durante il trattamento percutaneo degli aneurismi dell'aorta addominale.

PURPOSE: To evaluate the utility of a trans-brachial access during percutaneous treatment of abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: Since September 1998, 43 patients with AAA, have been treated using different types of endoprosthesis. A right trans-brachial access was performed in each patient to facilitate catheterization of the controlateral iliac limb and to make the advancement of the aortic device easier and safer. Moreover an angiographic catheter was positioned at renal arteries through the trans-brachial access. Then several angiographic controls were performed to check if the position of the endoprosthesis was correct. The catheterization of the iliac stump was performed using the retrograde technique in 31 cases (72%) and the anterograde one in 12 cases (27.9%). RESULTS: The percutaneous trans-brachial access was performed successfully in 42/43 patients. Only one case required surgical exposure. The procedure time for the trans-brachial access ranged from 2-12 min (mean 4.5). Trans-brachial access proved extremely useful in facilitating the aortic device advancement when the iliac-femoral axis was sharply angulated. This access allowed an easier catheterization of controlateral iliac limb. It also permitted several angiographic controls to check the correct position of the endoprosthesis. No pseudoaneurysms, no oculo-cerebral disease, no ischemic phenomena were observed during a 29 month follow-up. Only in 2 cases (4.6%) a small hematoma was noticed the day after the procedure. CONCLUSIONS: Trans-brachial access proved to be safe and useful during stent-graft positioning.

Clinical experience with covered wallstents for biliary malignancies: 23-month follow-Up.

PURPOSE: To evaluate the effectiveness of partially covered metallic Wallstents to prevent tumoral ingrowth in patients with neoplastic obstruction of the biliary tract. METHODS: Twenty-one patients with malignant obstructive jaundice have been treated with Wallstents partially covered with a polyurethane polymer. In total, 36 covered stents (8 and 10 mm in diameter, 70 and 90 mm long) were deployed. All the stents were free from covering at both ends. RESULTS: Jaundice was successfully treated in 100% of cases. There were no problems related to the releasing system during stent positioning, no major complications, and no incompatibility reactions to the materials composing the endoprostheses. At 23-month follow-up, 6 patients are still alive and 15 are dead; of these 15 patients, 11 died in the first 6 months and the last 4 died between 6 and 23 months. Seven patients had an obstructed stent; in four of these, cholangioscopy showed the presence of tumoral ingrowth and in one it showed necrotic tissue with biliary pigments and inflammatory cells. No biopsy specimen was obtained in the remaining two patients with stent obstruction. The follow-up, ranging from 7 to 23 months, showed a primary patency of 46.8% and 24.6% and an assisted patency of 66.3% and 59% at 6 months and 23 months, respectively. CONCLUSIONS: Covered metallic stents are effective and may produce improved survival in patients with malignant biliary obstruction (27. 8% at 23 months). Stent patency, however, is similar to that of uncovered stents. Modifications in the design of the covering membrane may reduce stent obstruction resulting from disruption of the plastic covering.

MR cholangiography in the examination of patients with biliary-enteric anastomoses.

OBJECTIVE: The aim of our study was to determine the role of MR cholangiography in the noninvasive examination of patients with biliary-enteric anastomoses. SUBJECTS AND METHODS: Twenty-four patients (nine men and 15 women; mean age, 68.9 years old) with biliary-enteric anastomoses underwent MR cholangiography. We used a fat-suppressed three-dimensional turbo spin-echo sequence (3000/700 [TR/TE]; echo train length, 128) with no breath-hold, optimized with a 0.5-T magnet. Imaging studies were performed because of scheduled follow-up (five patients), persistent jaundice (six patients), cholangitis and abnormal liver function (eight patients), and a combination of transient jaundice, epigastric pain, and abnormal liver function (five patients). RESULTS: Image quality was graded from optimal to good in 21 (88%) of 24 cases and poor in three (13%) of 24 cases. The degree of bile duct dilatation was correctly assessed, with complete agreement between the two observers in all cases. MR cholangiography correctly showed bile duct irregularities in six of the eight patients with cholangitis (kappa = .59), anastomotic strictures in all 19 patients with strictures (kappa = .86), and 3- to 15-mm stones in nine of 10 patients (kappa = .95). A slight overestimation of the strictures occurred in four of the 19 cases with strictures. CONCLUSION: MR cholangiography is a reliable imaging technique for the examination of patients with biliary-enteric anastomoses.

Prosthetic graft infection: diagnostic and therapeutic role of interventional radiology.

PURPOSE: Aortic graft infection is a rare complication of aortic surgery associated with high mortality and morbidity rates. The aim of the study was to evaluate the authors' experience with diagnostic and interventional procedures in the management of aortic graft infection. METHODS: Six patients with clinical signs suggestive of graft infection were studied. Abdominal computed tomography (CT) was performed in all patients. Diagnostic work-up was performed with perigraft puncture for fluid aspiration and contrast medium injection to confirm clinical signs or CT findings of graft infection, and to detect graft-enteric fistulas. Percutaneous drainage of the peri-prosthetic abscess was performed as attempted therapy in four patients. RESULTS: In four patients, CT examination findings were considered positive for graft infection. Culture and cytologic examination of aspirates revealed numerous white blood cells but did not show any growth. In three patients, direct contrast medium injection into the perigraft space allowed the detection of a graft-enteric fistula. In three patients, percutaneous drainage was performed as preoperative therapy, allowing improvement of the surgical outcome; in one patient the catheter was left in place as an attempt at definitive therapy, allowing a complete recovery. CONCLUSIONS: The percutaneous approach to prosthetic graft infection permits both the drainage and aspiration of the fluid in the perigraft area for laboratory studies. Percutaneous drainage can offer the possibility of definitive cure in patients for whom surgical management is considered too risky or, at least, represents a temporizing maneuver to improve the patient's general condition before surgery.

Self-expanding stents in transjugular intrahepatic portosystemic shunt: experience with nitinol Strecker stents.

The aim of our study was to evaluate the performance and efficacy of a new self-expanding stent (nitinol Strecker stent) in the transjugular intrahepatic portosystemic shunt (TIPS) procedure. We have successfully placed 64 nitinol Strecker stents in 48 patients. The average portosystemic gradient decreased from 22 to 11 mm Hg. Balloon dilatation was necessary in 12 of 35 angiographically controlled cases at 5 days (34%), because of incomplete stent expansion, small thrombi within the stent or obstruction. At 1-6 months stent malfunctions occurred in 8 of 23 patients who underwent control angiography (34%) and at 6-24 months in 6 of 7 patients (85%). Rebleeding occurred in 2 of 39 patients (follow-up > 1 month) (5%) and temporary crises of de novo encephalopathy were observed in 11 of 48 patients (23%). Refractory ascites completely resolved in 4 of 6 patients (66%) and improved in the remaining 2 cases. Compared with other self-expanding stents, nitinol Strecker stents seem to be equally effective in TIPS; no increase in complication rate was observed, either clinical or stent-related.

[Nonvascular interventional radiology in the treatment of post-liver transplant complications. The clinico-radiological correlations and technical considerations]. / La radiologia interventistica non vascolare nel trattamento delle complicanze post-trapianto epatico. Correlazioni clinico-radiologiche e considerazioni tecniche.

Eleven patients, included in a series of 105 orthotopic liver transplant recipients, underwent interventional radiologic procedures for post-operative complications. Seven patients had obstructive jaundice, three patients had sepsis, and one patient was bleeding from the T-tube. Cholangiography, performed in 9/11 patients, demonstrated stenosis of the anastomosis in six cases, stenosis of the intrahepatic biliary tree in one case, and stenosis of both tracts in the remaining two cases. Four patients were treated with bilioplasty (from 1 to 5 sessions), using balloon catheters (8-10 mm) followed by stones removal in one case, and by the placement of a metallic stent in another case. The follow-up ranged from one to three years: no biliary stasis occurred, during that period, in these patients. Another patient with recurrent cholangiocarcinoma of the biliary anastomosis, treated with Carey-Coons endoprosthesis and brachytherapy, died four months later without jaundice. In the three patients with sepsis and in the patient with bleeding from the T-tube, intra- or extra-hepatic (in one case) multiple abscesses were demonstrated. The conservative treatment with the placement of percutaneous drainage catheters, associated with internal biliary drainage in two cases, allowed complete symptoms resolution. The technical success obtained in all patients confirmed the effectiveness of interventional radiology in the treatment of biliary complications after liver transplant, thus avoiding the need of surgical reintervention.

Complications after laparoscopic cholecystectomy. Coordinated radiologic, endoscopic, and surgical treatment.

The diagnostic and therapeutic approaches used for patients referred for bile duct injuries and other major complications after laparoscopic cholecystectomy (LC) were reviewed and the results of a coordinated radiologic, endoscopic, and surgical approach were assessed. From April 1991 to October 1993, 23 patients were observed. Seven patients had biliary strictures, five had biliary lesions, five presented with retained common bile duct (CBD) stones, and one had a minor cystic duct leak. Five patients had miscellaneous abdominal fluid collections; in addition, biloma or bile ascites were present in 10/23 cases. Correct definition of iatrogenic lesions was mainly made by endoscopic retrograde cholangiography (ERCP) (n = 15), associated in six cases also with percutaneous cholangiography (PTC). "Minimally invasive" treatment included the full range of endoscopic and interventional radiological procedures. Six patients with biliary strictures, one patient with a biliary lesion, all five patients with residual CBD stones, and four patients with abdominal collections were treated by "minimally invasive" techniques: Therefore, laparotomy was avoided in 70% of cases (16/23 patients). Open surgery was necessary in 7/23 patients (30%), because of ductal lesion (n = 4), ductal stricture by endoloop (n = 1), iliac artery injury (n = 1), and phlegmon of gallbladder bed (n = 1). It appears that careful assessment of complications after LC is mandatory and often requires the combined use of ERCP/PTC and cross-sectional imaging.(ABSTRACT TRUNCATED AT 250 WORDS)

[Carbon dioxide as an intra-arterial contrast agent in echography: a technic for its preparation and the preliminary results in assessing hepatocarcinoma vascularization]. / Anidride carbonica come mezzo di contrasto intraarterioso in ecografia: tecnica di preparazione e risultati preliminari nella valutazione della vascolarizzazione dell'epatocarcinoma.

This paper reports on an original method to prepare a contrast agent consisting of CO2 microbubbles to be injected i.a. during ultrasound examinations (ultrasound angiography-USA), whose value was investigated in the study of tumor neovascularity in HCC patients. Thirty-five HCC patients underwent USA. CO2 was drawn out from a gas container under pressure and, through a sublimation process, made available in predetermined quantities in test tubes. USA was performed during angiography in 9 cases and immediately before arterial chemoembolization in the other 26 cases. In 51 lesions vascularity was evaluated with conventional angiography, USA and lipiodol CT. USA demonstrated lesion hypervascularity in 91% of cases, as confirmed by lipiodol CT (88%), versus 72.4% of angiography. In 3 of 35 patients USA demonstrated 6 more lesions undetected by other modalities: two of them were proved to be HCC and adenomatous hyperplasia at percutaneous biopsy. USA is a cost-effective procedure, which is easy to perform during conventional angiography: it is more sensitive than conventional angiography in the study of lesion neovascularity and can help plan lesion management, anticipating the results of chemoembolization. The role of USA in the diagnosis and treatment of HCC is, however, still to be defined.