Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP.

This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.

Everolimus prevents coronary microvasculopathy in heart transplant recipients with normal coronary angiograms: an anatomo-functional study.

BACKGROUND: Coronary allograft vasculopathy (CAV) involves both epicardial vessels and coronary microcirculation. Little is known about the effect of everolimus on coronary microvasculopathy in heart transplantation (HT). The aim of our study was to assess the pathological substrate of coronary flow reserve (CFR) impairment in HT patients and the effect of everolimus on microvascular remodeling and CFR. METHODS: We studied 28 HT patients with normal coronary angiograms (25 male, age at HT 54±10 years). Immunosuppressive regimen consisted of cyclosporine and everolimus (10 patients) or mycophenolate mophetil (18 patients). They were evaluated with digital microscopy for morphometric analysis of fibrosis and microvascular remodeling. Coronary flow velocity in the left anterior descending coronary artery was detected using transthoracic Doppler echocardiography at rest and during adenosine infusion. CFR was the ratio of hyperaemic diastolic flow velocity (DFV) to resting DFV. A CFR≤2.5 was considered abnormal and sign of coronary microvascular dysfunction. RESULTS: In patients with CFR≤2.5 the thickness of the tunica media of intramyocardial arterioles was greater than in patients with CFR>2.5 (39±2 vs 17±3 µm; P=.02). Microvascular remodeling was significantly higher in patients with CFR≤2.5 (72.7±2.4 vs 50.4±8.4%; P<.007). Capillary density and fibrosis were comparable between groups (157.2±42.4 vs 175.7±42.4 capillaries/mm2; P=.3; and 6.8±5 vs 8.3±4.9%; P=.4, respectively). The thickness of the tunica media of intramyocardial arterioles was lower in patients whose therapy included everolimus (15±2 vs 32±4 µm, P=.03) and CFR was higher (3.2±0.5 vs 2.8±0.9; P=.03). CONCLUSION: The pathological substrate of reduced CFR in HT patients seems to be a hypertrophic remodeling of coronary arterioles. Everolimus appears to prevent such microvascular remodeling and preserve coronary flow reserve.

HLA-DRB1 typing by micro-bead array assay identifies the origin of early lymphoproliferative disorder in a heart transplant recipient.

We report the case of a 68-year-old woman who underwent heart transplantation for hypertrophic cardiomyopathy. Two months after the transplant she developed mild fever and dyspnea with a marked drop in left ventricle ejection fraction of 31%. Coronary angiography was negative for cardiac allograft vasculopathy. Endomyocardial biopsy revealed ischemic damage with no evidence of acute cellular rejection, antibody-mediated rejection or viral myocarditis. A neoplastic process was suspected even though full-body computerized tomography was negative for malignancy. The patient died 4 months after transplantation. The autopsy showed acute antero-septal myocardial infarction due to a nodular epicardial EBV-related posttransplant lymphoproliferative disorder (PTLD) infiltrating the left anterior descending coronary artery with occlusive neoplastic thrombosis. We highlight two major aspects of this case: (1) the unusual occurrence of early PTLD involving the cardiac allograft and causing a fatal outcome, (2) the application of an immunological technique for HLA-DRB1 typing to posttransplant paraffin-embedded autopsy material to identify the recipient origin of this early malignancy, thus excluding a possible donor-transmitted neoplasm.

Post-transplant lymphoproliferative disorders after heart or kidney transplantation at a single centre: presentation and response to treatment.

Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining 20, the efficacy and safety of a weekly anthracycline-based chemotherapy were assessed. Sixteen patients obtained a complete remission. One death was related to treatment. With a median follow-up of 36 months, 3-year overall survival was 63.3% and 57% for the entire group and the chemotherapy-treated group, respectively. Moreover, 4 second neoplasms were observed in the chemotherapeutic group. In this study, we demonstrated that most PTLD need other treatment than RI and a weekly regimen is manageable and has a favourable impact on long-term survival.

Medullary sponge kidney (Lenarduzzi-Cacchi-Ricci disease): a Padua Medical School discovery in the 1930s.

The introduction of radiological contrast media and intravenous (i.v.) urography in clinical diagnostics in the 1930s enabled the discovery of several diseases, including the medullary sponge kidney (MSK). MSK is a renal malformation characterized by cystic anomalies of precalyceal ducts, which is frequently associated with nephrocalcinosis and renal stones. Although it was first recognized by G Lenarduzzi in 1939, its thorough description was the result of the ante litteram multidisciplinary cooperation between a radiologist (Lenarduzzi), a urologist (Cacchi), and a pathologist (Ricci), all at the Padua University Hospital. These authors 'established' the paradigm for its diagnosis that is still used today. I.v. urography is the gold standard for the diagnosis of MSK, but as the technique is used less and less, there is a concrete possibility of this renal condition being forgotten in the future. Although the pathogenesis of MSK has yet to be elucidated, its association with different malformative conditions supports the idea that it is a developmental disorder. Recent findings suggest that MSK may be the consequence of a disruption of the ureteral-bud/metanephric-blastema interface.

[Determination of interleukin-8 in induced sputum of workers exposed to low concentrations of asbestos]. / Determinazione dell'interleuchina-8 nell'espettorato indotto di lavoratori esposti a basse concentrazioni di asbesto.

The concentration of interleukin-8 (IL-8) in the induced sputum of 17 workers exposed to low airborne asbestos levels and of 10 controls was determined. IL-8 levels were statistically significantly increased in the asbestos exposed group compared to controls. This finding underlines the usefulness of the study of proinflammatory mediators as possible predictors of alveolar damage.

[Endovascular treatment for recurrent carotid stenosis]. / Il trattamento endovascolare della restenosi carotidea.

PURPOSE: Surgery of recurrent carotid stenosis (RCS) has higher complication rates than primary carotid endoarterectomy (CEA). Percutaneous transluminal angioplasty (PTA) and stent placement were evaluated retrospectively with a view to proposing then as alternative procedures for RCS. METHODS: In the last 10 years, 19 patients underwent 20 endovascular procedures for RCS at our Department. The mean interval between CEA and PTA was 21 months (range 4-96): 14 patients had PTA within 2 years, 3 patients within 2 and 3 years,and 2 after 3 years. The mean degree of stenosis was 92% (range 80-95%). PTA was performed by balloon catheters (size 4-7 mm) without using cerebral protection device; one self-expanding stent was used to treat RCS after PTA. All patients underwent physical examination and carotid color-coded Doppler sonography in autumn 1999 RESULTS: The procedure was technically successful, with residual stenosis lower than 50%, in 17 of 19 patients; 10 patients showed residual stenosis lower than 30%. Carotid PTA was stopped due to transient neurological deficit in one case. One RCS proved uncompliant even though high-pressure balloon catheters were used. The mean follow-up period in 16 patients was 37.4 months (range 3-99 months). Carotid restenosis after PTA developed in 3 patients, respectively after 29,18 and 7 months. In the last case RCS was successfully treated by stent placement (Wallstent). The primary patency rate was 81%, the secondary patency rate was 88% and the late clinical success rate was of 94%. CONCLUSIONS: In selected cases, PTA without the use of cerebral protection devices and stent placement proved to be a safe and effective alternative treatment for early RCS. When an atherosclerotic lesion is suspected surgery or endovascular treatment with cerebral protection devices are recommended.

Identification of the etiology of primary aldosteronism with adrenal vein sampling in patients with equivocal computed tomography and magnetic resonance findings: results in 104 consecutive cases.

The objectives of this study were to investigate the usefulness of adrenal vein sampling in identifying the etiology of primary aldosteronism (PA) in patients with equivocal CT and MR findings. Between 1990 and 1999, 104 referred hypertensive patients (45 women and 59 men, aged 49.6 +/- 11.6 yr) were diagnosed to have PA with inconclusive computed tomography scan and magnetic resonance results, based on established criteria. Adrenal vein sampling (AVS) for measurement of plasma aldosterone (A) and cortisol (C) levels was performed in all. Selectivity of AVS was assessed by the ratio between C levels in each adrenal vein and in the infrarenal inferior vena cava plasma (C(side)/C(IVC)). A receiver operator characteristics analysis was carried out to establish 1) the best AVS-derived index, 2) the degree of selectivity that could provide an accurate diagnosis, and 3) whether a correct diagnosis could be made from a unilaterally selective AVS. An aldosterone-producing adenoma (average diameter, 12.2 +/- 0.08 mm) was eventually diagnosed in 41 patients (39.4%) and was excluded in the rest. Adrenal vein rupture leading to partial adrenal loss occurred in 1 patient (0.9% complication rate). By assuming a cut-off value of C(side)/C(IVC) > or = 1.1, AVS was selective in 85.7% and 94.1% of cases on the right and left sides, respectively, and bilaterally in 80.6% of cases. Of all AVS-derived indexes, the A/C of one over the A/C contralateral side [(A/C)(side)/(A/C)(contralateral side)] furnished the best diagnostic accuracy. With a bilaterally selective AVS, a value of (A/C)(side)/(A/C)(contralateral side) > or = 2 provided a conclusive etiological diagnosis of PA in 79.7% of cases. At variance, no accurate diagnosis could be made from unilaterally selective AVS. AVS was feasible and safe in most PA patients with inconclusive computed tomography and magnetic resonance scans. When bilaterally selective (i.e. C(side)/C(IVC) > or = 1.1) a ratio of (A/C)(side)/(A/C)(control) > or = 2 provided the best compromise of sensitivity and false positive rate for lateralization of the etiology of PA.

Sulfinpyrazone reduces cyclosporine levels: a new drug interaction in heart transplant recipients.

BACKGROUND: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. METHODS: We studied 120 HT recipients (109 men; mean age at HT, 52+/-10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59+/-41 months. We stopped the drug after 6+/-2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. RESULTS: Mean uricemia decreased with allopurinol (0.58+/-0.12 vs. 0.41+/-0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51+/-0.13 vs. 0.40+/-0.12 mmol/liter, p = 0.0001). Mean creatinine increased (171+/-42 and 164+/-35 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/liter, p = NS). Mean urea did not change with allopurinol (14+/-5 vs. 15+/-7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01+/-5 vs. 12.60 +/-5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193+/-73 vs. 188+/-65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7+/-0.8 vs. 2.6+/-0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183+/-89 vs. 121 +/-63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/-0.9 vs. 2.8+/-0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.

Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.

BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.

Quantitative ultrasound at the hand phalanges: comparison with quantitative computed tomography of the lumbar spine in postmenopausal women.

The aim of our study was to evaluate the diagnostic effectiveness of a quantitative ultrasound technique for measuring bone tissue at the proximal phalanges of the non-dominant hand. We correlated the mean value of the amplitude-dependent speed of sound (AD-SoS) and the ultrasound bone profile score (UBPS) measured at the phalanges with bone mineral density (BMD) of the lumbar spine gauged with quantitative computed tomography (QCT). We studied a group of 177 postmenopausal women consecutively presenting for osteoporosis screening. We observed that in the whole study group both AD-SoS and UBPS correlated weakly with BMD, although with statistical significance (r = 0.54 and r = 0.45, respectively; p < 0.0001). The same parameters showed a poor correlation (r = 0.48, p < 0.0001; and r = 0.23, p = 0.017) in the group of patients which QCT has classified as osteoporotic. Finally, no correlation was found in the rest of our population. The correlation coefficients of comparison between our QUS and QCT measurements are not strong enough to allow us a prediction of one measure from the other. Therefore, we do not consider the phalangeal osteosonography a valid substitute of QCT technique for assessment of bone status in postmenopausal women.

Skin cancer in heart transplant recipients: frequency and risk factor analysis.

BACKGROUND: The frequency of skin cancer is increased among organ transplant recipients, but the predisposing risk factors are controversial. It is also unclear whether heart transplant patients face an increased risk compared to recipients of other organs, e.g. kidney transplants. METHODS: We performed univariate and multivariate analysis of risk factors for skin cancer in 252 heart transplants and in a control series of 228 kidney transplants followed up at a single center. An extensive dermatologic examination was carried out; baseline features, type of immunosuppression, number of 3A rejection episodes, extent of sunlight exposure and skin type were recorded. Multivariate analysis (Cox regression) included: age at transplantation, sex, skin type (Fitzpatrick's criteria), presence of solar keratosis, presence of warts, type of organ, sunlight exposure. RESULTS: During follow up skin cancer was more common among heart transplants (40, 16 %) than in kidney transplants (16, 7%, p = 0.004). The cumulative incidence of skin cancer by life table analysis increased from 16% after 5 years to 33% after 10 years in heart transplant patients and from 6% to 17% in kidney transplants (p 10000 hours (relative risk = 2.8), but not organ type were significant risk factors. CONCLUSION: Age at transplant, skin type and sunlight exposure, but not type of organ and type of immunosuppressive regimen, are associated with increased risk of skin cancer in heart transplantation.

[Responsibility (according to the legislative act "626/1994") in the implementation of preventive measures in the preparation of antiblastic drugs]. / Le responsabilità (ai sensi del d.lgs. "626/1994") nell'attuazione delle misure preventive per la preparazione di farmaci antiblastici.

The 7th title of the legislative act "626/1994" (and the other normative indications) identifies cavcingenic agents in occupational uses, and also the protections of workers in exposure. Among these agents there are any antiblastic drugs. This is a difficult problem for a correct application of normative indications: it's no possible to replace cavcingenic agents with no cavcingenic agents, as so as it's impossible to operate on "closed cycle". The authors put the attention on the other very important normative indications: "preparations in bordered and isolated room", "minimal exposure", "severe procedures and internal normations", formal "identification of the responsibilities" in the hospital organization (also with the strictly identification of managers and foremen).

Extracorporeal photochemotherapy after cardiac transplantation: a new therapeutic approach to allograft rejection.

UNLABELLED: Photopheresis (ECP) is a new immunomodulatory therapy in which recipient lymphocytes are treated extracorporeally with 8-methoxypsoralen and ultraviolet light. The treatment seems to induce an inhibition of both humoral and cellular rejection after transplantation. OBJECTIVE: Since recurrent rejection (RR) continues to be a severe complication after heart transplantation (HTx) and the immunosuppressive regimes used for the treatment are often associated with increased morbidity and mortality, we investigated whether ECP could have a beneficial effect on the number and severity of rejection episodes. METHODS: Eleven HTX recipients (5 M and 6 F, mean age 48.5 yrs) with RR were enrolled in the study. ECP was performed at weekly intervals during the 1st month, at 2 week intervals during the 2nd and 3rd month, and then monthly for another 3 months. RESULTS: The fraction of biopsies (EMB) with a grade 0/1A rejection increased during ECP from 46% to 72% while the EMB showing a 3A/3B rejection decreased from 42% to 18%. It is also noteworthy that out of the 78 EMB performed during ECP only one showed a 3B rejection in comparison with 13 out of 110 EMB in the pre-ECP period. Six rejection relapses were observed in a total follow-up of 60 months, two of them occurring during the tapering of oral steroid. Four relapses were reversed by ECP, one by i.v. steroids and the last by methotrexate after the failure of both i.v. steroids and ECP. The mean doses of immunosuppressive drugs resulted lower after 6 months of ECP: steroids were reduced from 13 to 8.25 mg/day, cyclosporine from 375 to 285 mg/day, azathioprine from 55 to 35 mg/day. CONCLUSIONS: ECP is a well tolerated treatment. Its administration allows better RR control and significant reduction in immunosuppressive therapy.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in patients with Child's grade A or B cirrhosis: a multivariate analysis of prognostic factors.

We evaluated factors affecting long-term survival after transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) complicating cirrhosis. One hundred eighty-two patients with Child's class A or B cirrhosis and an HCC, not amenable to surgery or percutaneous ethanol injection, underwent 346 TACEs (mean 1.9) with epirubicin, iodized oil, and gelatin sponge. Many prognostic factors were subjected to univariate analysis and thereafter, when significant, to the Cox's hazard proportional model. Finally, the significant indices in the Cox's model were used to estimate the accuracy of the probability of death with computation of the area under the receiving operative characteristic (ROC) curve. The cumulative survival rates at 1, 2, 3, and 5 years were 0.83, 0.52, 0.40, and 0.16, respectively. According to Cox's model, the factors associated with significantly worse survival were the presence of ascites (p = 0.0027), elevated bilirubin levels (p = 0.0163), elevated alpha-fetoprotein (alphaFP) values (p = 0.0067), a tumor greater than 5 cm in diameter (p = 0.0001), and the absence of a tumor capsule-like rim (p = 0.0278). According to these parameters, the accuracy of the probability of death estimated with ROC analysis was 0.63. Minor and major complications occurred in 82 patients (45%) and caused death in 2 patients. Long-term prognosis after TACE for HCCs in patients with Child's class A or B cirrhosis depends on the presence of ascites, the bilirubin level, the alphaFP value, the diameter of the tumor, and the presence of a tumor capsule-like rim. However, when considered altogether, these variables are poor predictors to evaluate survival, and other factors should be investigated to identify subjects more responsive to TACE. Complications occur in a high percentage of patients, but they do not affect long-term prognosis.

Radiological evidence of subclinical dysphagia in motor neuron disease.

Dysphagia in motor neuron disease (MND) may lead to dangerous complications such as cachexia and aspiration pneumonia. Functional evaluation of the oropharyngeal tract is crucial for identifying specific swallowing dysfunctions and planning appropriate rehabilitation. As part of a multidisciplinary study on the treatment of dysphagia in patients with neuromuscular diseases, 23 MND patients with different degrees of dysphagia underwent videofluoroscopy, videopharyngolaryngoscopy and pharyngo-oesophageal manometry. The results of the three instrumental investigations were analysed in order (1) to define the pattern of swallowing in MND patients complaining of dysphagia; (2) to evaluate whether subclinical abnormalities may be detected; and (3) to assess the role of videofluoroscopy, videopharyngolaryngoscopy and manometry in the evaluation of MND patients with deglutition problems. Correlations between the instrumental findings and clinical features (age of the patients, duration and severity of the disease, presence and degree of dysphagia) were also assessed. The results of our study showed that: (1) The oral phase of deglutition was compromised most often, followed by the pharyngeal phase. (2) In all patients without clinical evidence of dysphagia, subclinical videofluoroscopic alterations were present in a pattern similar to that found in the dysphagic group. (3) Videofluoroscopy was the most sensitive technique in identifying oropharyngeal alterations of swallowing. Impairment of the oral phase, abnormal pharyngo-oesophageal motility and incomplete relaxation of the upper oesophageal sphincter were the changes most sensitive in detecting dysphagia. Videofluoroscopy was also capable of detecting preclinical abnormalities in non-dysphagic patients who later developed dysphagia. Practical guidelines for the use of instrumental investigations in the assessment and management of dysphagia in MND patients are proposed.

[Long-term results of chemoembolization for hepatocarcinoma]. / Risultati a lungo termine della chemioembolizzazione nell'epatocarcinoma.

We reviewed the long-term results of transcatheter arterial chemoembolization in the treatment of inoperable hepatocellular carcinoma (HCC) complicating cirrhosis; the survival analysis was used to assess the clinical efficacy of the procedure. Several chemoembolization protocols are discussed because no standard treatment exists. Literature data show cumulative survival rates after chemoembolization for an HCC to range 60% to 80% at one year and 40% to 50% at two years; comparative studies, although contradictory, show a trend of chemoembolization to prolong survival in patients with inoperable carcinoma. The main prognostic factors are tumor size and extent, liver function impairment, the grade of Lipiodol tumor uptake, and the tumor response to therapy. The complication rates of chemoembolization vary largely in the literature, mainly because of the different standards used to define adverse events. Chemoembolization morbility rate is usually high, ranging 20% to 55%, but most complications are generally well treated with conservative management. The mortality rate is usually very low and well acceptable for a palliative anticancer therapy. In conclusion, chemoembolization is clinically effective in prolonging survival in cirrhotic patients with HCC; the lack of any reliable alternative therapy makes chemoembolization play a major role in the treatment of HCC when surgery or percutaneous ethanol injection are unfeasible.