F. Giuliante

CD133+ stem cell mobilization after partial hepatectomy depends on resection extent and underlying disease.

BACKGROUNDnBone marrow stem cells (BMSC) can participate to liver regeneration. However, conflicting results have been reported on this topic in patients undergoing liver resection.nnnAIMSnTo assess the impact of liver resection extent and presence of underlying liver disease in modulating BMSC mobilization.nnnMETHODSnWe enrolled 29 patients undergoing liver resection of different extents, 5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by flow cytometry at different time-points after surgery. The hepatic commitment of mobilized BMSC was investigated by polymerase chain reaction. Liver specimens were collected during surgery for histopathological analysis. Hepatocyte growth factor and granulocyte-colony stimulating factor serum levels were measured by enzyme-linked immunosorbent assay.nnnRESULTSnBMSC mobilization was found in patients undergoing major liver resection, especially in the presence of underlying disease. Ductular reactions were noted in patients with chronic hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM, cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte-colony stimulating factor levels increased following liver resection and the contemporaneous presence of liver disease was associated with their highest raise.nnnCONCLUSIONSnLiver repair is mainly an endogenous process. BMSC become important in case of extensive resection, especially in the presence of underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte growth factor and granulocyte-colony stimulating factor seem to be involved in the dynamics underlying hepatic regeneration and BMSC recruitment.

Liver Resection versus Radiofrequency Ablation plus Transcatheter Arterial Chemoembolization in Cirrhotic Patients with Solitary Large Hepatocellular Carcinoma

PURPOSEnTo compare liver resection (LR) with single-step, balloon-occluded radiofrequency (RF) ablation plus drug-eluting embolics transarterial chemoembolization in cirrhotic patients with single hepatocellular carcinoma (HCC) ≥ 3 cm.nnnMATERIALS AND METHODSnFrom 2010 to 2014, 25 patients with compensated cirrhosis and single HCC ≥ 3 cm (median size 4.5 cm; range, 3.0-6.8 cm) not suitable for LR or liver transplantation were treated with RF ablation plus transarterial chemoembolization in a prospective observational single-center pilot study; all patients had complete tumor necrosis after treatment. A retrospective control group included 29 patients (median HCC size 4.0 cm; range, 3.0-7.4 cm) who underwent LR. RF ablation plus transarterial chemoembolization group included more patients with severe portal hypertension (65.5% vs 35.0%, Pxa0= .017). Primary endpoints were overall survival (OS) and tumor recurrence (TR) rates.nnnRESULTSnOne death and 1 major complication (4%) were observed in LR group. No major complications were reported in RF ablation plus transarterial chemoembolization group (Pxa0= .463). OS rates at 1 and 3 years were 91.8% and 79.3% in LR group and 89.4% and 48.2% in RF ablation plus transarterial chemoembolization group (Pxa0= 0.117). TR rates at 1 and 3 years were 29.5% and 45.0% in LR group and 42.4% and 76.0% in RF ablation plus transarterial chemoembolization group (Pxa0= .034). Local tumor progression (LTP) rates at 3 years were significantly lower in LR group (21.8% vs 58.1%, Pxa0= .005). Similar results were found in patients with HCC ≤ 5 cm (TR rates 35.4% vs 75.1%, Pxa0= .016; LTP 16.0% vs 55.7%, Pxa0= .013).nnnCONCLUSIONSnLR achieved lower TR and LTP rates than RF ablation plus transarterial chemoembolization, but 3-years OS rates were not statistically different between the 2 groups. RF ablation plus transarterial chemoembolization is an effective treatment option in patients with compensated cirrhosis and solitary HCC ≥ 3 cm unsuitable for LR.

Comparison of the 7th and 8th editions of the American Joint Committee on Cancer Staging Systems for perihilar cholangiocarcinoma

Background: The performances of the American Joint Committee on Cancer staging systems of the 7th and 8th edition were compared using a cohort of patients undergoing surgery for perihilar cholangiocarcinoma at 2 tertiary referral Italian hepatobiliary centers. Methods: The American Joint Committee on Cancer 7th and 8th edition staging systems were used to classify 214 patients who underwent surgery for perihilar cholangiocarcinoma. The performances of the 2 staging systems were compared using the concordance index. Results: Using the American Joint Committee on Cancer 7th edition staging system, we found that the 5‐year overall survival for stages I, II, and IVa was 71%, 34%, and 34%, while no patients in stages IIIa, IIIb, and IVb survived 5 years. In comparison, when the American Joint Committee on Cancer 8th edition staging system was used, the 5‐year overall survival was 71% and 35% in stages I and II, resulting in 23%, 19%, and 22% in stages IIIa, IIIb, and IIIc, respectively. Of note, no patients in stages IVa and IVb survived 5 years. The American Joint Committee on Cancer 8th edition staging system had a slightly better discriminatory ability with a concordance index of 0.624 compared with 0.619 for the American Joint Committee on Cancer 7th edition. Conclusion: The newly released classification American Joint Committee on Cancer 8th edition staging system demonstrated a poor to moderate ability to predict prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma, which was only slightly better than the previous edition. Further refinements are needed to improve the prognostic ability of the American Joint Committee on Cancer staging system for perihilar cholangiocarcinoma.

Posterior Right Disconnected Bile Duct

A 50-year-old woman was referred to our tertiary Hepato-Pancreato-Biliary (HPB) Surgery Center two years after undergoing a complex cholecystectomy (Mirizzi Syndrome Type 2) with T-Tube placement in the common bile duct after an episode of mild cholangitis. Cross-sectional imaging revealed sectoral dilatation of the right posterior bile duct. Focal intrahepatic strictures often present with vague symptoms such as fever, jaundice, or abdominal pain. A differential diagnosis based on the patient’s clinical history and basic imaging data should take into consideration iatrogenic and non-iatrogenic causes of segmental cholangiectasia. Given the difficulty in ruling out malignancy (which occurs in 50–70% of the cases of isolated cholangiectasia) a liver resection should be considered, since it can provide both the data necessary for a definitive diagnosis allowing an oncologically correct treatment plan.

Single-step multimodal locoregional treatment for unresectable hepatocellular carcinoma: balloon-occluded percutaneous radiofrequency thermal ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE)@@@Terapia loco-regionale multimodale dell’epatocarcinoma non resecabile con approccio single-step: termoablazione a radiofrequenza durante occlusione temporanea dell’arteria epatica con catetere da PTA (BO-RFA) plus chemioembolizzazione arteriosa transcatetere (TACE)

PurposeThis study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion >3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year.Methods and materialsThis pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion >3 cm (range, 3.5–6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed.ResultsNo major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5–5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5–1.3cm).ConclusionsTACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.RiassuntoObiettivoValutare nei pazienti affetti da epatocarcinoma multinodulare unilobare non resecabile, con almeno una lesione con diametro >3 cm, la fattibilità, la sicurezza e l’efficacia di una nuova terapia combinata con RFA durante occlusione arteriosa con catetere per PTA (BO-RFA) seguita da TACE della lesione principale e TACE delle restanti lesioni, in un’unica seduta. Endpoint secondario del nostro studio è stata la comparazione degli effetti iniziali in termini di necrosi tumorale delle lesioni trattate con questa nuova terapia combinata con quelli ottenuti in una popolazione di confronto trattata nel nostro centro nell’anno precedente con sola TACE.Materiali e metodiIl nostro studio pilota è stato approvato dal comitato etico e dall’autorità competente, e per tutti i pazienti è stato ottenuto un consenso informato scritto. Dieci pazienti consecutivi affetti da HCC multinodulare (2–6 noduli) unilobare, non resecabile e con una lesione target di diametro >3 cm di diametro (range 3,5–6 cm), non suscettibile di trattamenti di tipo curativo, sono stati arruolati nel nostro studio pilota monocentrico multidisciplinare. Il piano di trattamento è stato: RFA (ago con punta esposta da 3 cm) della lesione target durante occlusione endovascolare dell’arteria epatica afferente al tumore con catetere per PTA seguita da una TACE selettiva della stessa, più una TACE lobare per il trattamento delle altre lesioni (450 mg di carboplatino più lipiodol associato a embolizzazione temporanea con spongostan). Gli eventi avversi, cosÌ come le complicanze intra- e periprocedurali sono stati valutati clinicamente. L’efficacia locale in fase precoce è stata valutata mediante TC multifasica eseguita a un mese dalla procedura, sulla base dei criteri m-RECIST; separatamente è stata, inoltre, effettuata una valutazione delle lesioni target in termini di enhancement, diametro dell’area necrotica e presenza e distribuzione di lipiodol.RisultatiNon si sono verificate complicanze maggiori. Il successo tecnico complessivo, definito come la completa devascolarizzazione di tutti i noduli in fase arteriosa, è stato ottenuto in 7/10 pazienti con 3 risposte parziali (persistenza di piccoli noduli ipervascolarizzati). Considerando solo le lesioni target, il successo tecnico è stato raggiunto in tutti i pazienti, con la presenza di un’area priva di enhancement nella zona corrispondente al precedente nodulo di HCC (diametro necrotico 3,5–5 cm), con un accumulo periferico di lipiodol circonferenziale (margine di sicurezza), di almeno 0,5 cm (0,5–1,3 cm).ConclusioniIl trattamento combinato con BO-RFA seguita da TACE, in un approccio single-step, sembra essere una terapia sicura ed efficace per il trattamento dell’HCC avanzato non resecabile, permettendo di ottenere un alto tasso di risposta locale completa anche in lesioni di grandi dimensioni.

Terapia loco-regionale multimodale dell'epatocarcinoma non resecabile con approccio single-step: termoablazione a radiofrequenza durante occlusione temporanea dell'arteria epatica con catetere da PTA (BO-RFA) plus chemioembolizzazione arteriosa transcatetere (TACE)

PurposeThis study was undertaken to evaluate the feasibility, safety and efficacy of a new combined single-step therapy in patients with unresectable multinodular unilobar hepatocellular carcinoma (HCC), with at least one lesion >3 cm, with balloon-occluded radiofrequency ablation (BO-RFA) plus transcatheter arterial chemoembolization (TACE) of the main lesion and TACE of the other lesions. The second purpose of our study was to compare the initial effects in terms of tumour necrosis of this new combined therapy with those obtained in a matched population treated with TACE alone in a singlestep treatment in our centre in the previous year.Methods and materialsThis pilot study was approved by the institutional review board, and informed consent was obtained from all patients. Ten consecutive patients with multinodular (two to six nodules) unilobar unresectable HCC and with a main target lesion >3 cm (range, 3.5–6 cm) not suitable for curative therapy were enrolled in our single-centre multidisciplinary pilot study. The schedule consisted of percutaneous RFA (single 3-cm monopolar needle insertion) of the target lesion during occlusion of the hepatic artery supplying the tumour, followed by selective TACE, plus lobar TACE for other lesions (450-mg carboplatin and lipiodol plus temporary embolisation with SPONGOSTAN). Adverse events and intra- and periprocedural complications were clinically assessed. Early local efficacy was evaluated on 1-month follow-up multiphasic computed tomography (CT) on the basis of the Modified Response Evaluation Criteria in Solid Tumors (m-RECIST). A separate evaluation of target lesions in terms of enhancement, necrotic diameter and presence and distribution of lipiodol uptake was also performed.ResultsNo major complications occurred. Overall technical success, defined as complete devascularisation of all nodules during the arterial phase, was achieved in seven of 10 patients, with three cases of partial response (persistence of small hypervascular nodules). When considering only target lesions, technical success was obtained in all patients, with a nonenhancing area corresponding in shape to the previously identified HCC (necrotic diameter, 3.5–5 cm) and with circumferential peripheral lipiodol uptake (safety margin) of at least 0.5 cm (0.5–1.3cm).ConclusionsTACE and BO-RFA, plus TACE in a singlestep approach seems to be a safe and effective combined therapy for treating advanced, unresectable HCC lesions, allowing a high rate of complete local response to be achieved in large lesions also.RiassuntoObiettivoValutare nei pazienti affetti da epatocarcinoma multinodulare unilobare non resecabile, con almeno una lesione con diametro >3 cm, la fattibilità, la sicurezza e l’efficacia di una nuova terapia combinata con RFA durante occlusione arteriosa con catetere per PTA (BO-RFA) seguita da TACE della lesione principale e TACE delle restanti lesioni, in un’unica seduta. Endpoint secondario del nostro studio è stata la comparazione degli effetti iniziali in termini di necrosi tumorale delle lesioni trattate con questa nuova terapia combinata con quelli ottenuti in una popolazione di confronto trattata nel nostro centro nell’anno precedente con sola TACE.Materiali e metodiIl nostro studio pilota è stato approvato dal comitato etico e dall’autorità competente, e per tutti i pazienti è stato ottenuto un consenso informato scritto. Dieci pazienti consecutivi affetti da HCC multinodulare (2–6 noduli) unilobare, non resecabile e con una lesione target di diametro >3 cm di diametro (range 3,5–6 cm), non suscettibile di trattamenti di tipo curativo, sono stati arruolati nel nostro studio pilota monocentrico multidisciplinare. Il piano di trattamento è stato: RFA (ago con punta esposta da 3 cm) della lesione target durante occlusione endovascolare dell’arteria epatica afferente al tumore con catetere per PTA seguita da una TACE selettiva della stessa, più una TACE lobare per il trattamento delle altre lesioni (450 mg di carboplatino più lipiodol associato a embolizzazione temporanea con spongostan). Gli eventi avversi, cosÌ come le complicanze intra- e periprocedurali sono stati valutati clinicamente. L’efficacia locale in fase precoce è stata valutata mediante TC multifasica eseguita a un mese dalla procedura, sulla base dei criteri m-RECIST; separatamente è stata, inoltre, effettuata una valutazione delle lesioni target in termini di enhancement, diametro dell’area necrotica e presenza e distribuzione di lipiodol.RisultatiNon si sono verificate complicanze maggiori. Il successo tecnico complessivo, definito come la completa devascolarizzazione di tutti i noduli in fase arteriosa, è stato ottenuto in 7/10 pazienti con 3 risposte parziali (persistenza di piccoli noduli ipervascolarizzati). Considerando solo le lesioni target, il successo tecnico è stato raggiunto in tutti i pazienti, con la presenza di un’area priva di enhancement nella zona corrispondente al precedente nodulo di HCC (diametro necrotico 3,5–5 cm), con un accumulo periferico di lipiodol circonferenziale (margine di sicurezza), di almeno 0,5 cm (0,5–1,3 cm).ConclusioniIl trattamento combinato con BO-RFA seguita da TACE, in un approccio single-step, sembra essere una terapia sicura ed efficace per il trattamento dell’HCC avanzato non resecabile, permettendo di ottenere un alto tasso di risposta locale completa anche in lesioni di grandi dimensioni.

634 BALLOON-OCCLUDED PERCUTANEOUS RADIO-FREQUENCY THERMAL ABLATION (RFA) PLUS TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE): A NEW COMBINED SINGLE-STEP THERAPY FOR TREATMENT OF MULTINODULAR UNRESECTABLE HEPATOCELLULAR CARCINOMA

Poster: ECR 2011 / C-1782 / Balloon-occluded percutaneous radio-frequency thermal ablation (RFA) plus transcatheter arterial chemoembolization (TACE): a new combined single-step therapy for treatment of unresectable hepatocellular carcinoma by: R. Iezzi, G. L. Rapaccini, A. M. De Gaetano, M. Pompili, A. Gasbarrini, L. Bonomo; Rome/IT