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In the last two decades, there has been marked development in virtual slide technology as well as its application in various subspecialties of pathology. In particular, there have been several studies examining the utility of whole slide imaging (WSI) in breast and gynecological pathology. The aim of this systematic review is to analyse published evidence regarding validation studies of WSI applied specifically to the female genital tract and breast pathology.A systematic search was carried out in Pubmed and Embase databases and studies dealing with the validation of a WSI system for breast and gynaecological pathology. The topics evaluated concerned expertise of engaged pathologists, varied specimens, scanners, washout period, experience viewing WSI, and diagnostic concordance of WSI to traditional light microscopic diagnoses.Of 1467 publications retrieved, 23 studies were included. Most of these studies concerned breast pathology. Validation guidelines recommended by the College of American Pathologists pertaining to a dataset of at least 60 cases, washout period, and recording intra-observer variability were followed by most studies. Major challenges encountered with WSI included difficulty identifying high-grade nuclear atypia and mitotic count for borderline ovarian tumors, interpretation of squamous intraepithelial lesions in liquid-based cervical cytology, and grading breast cancer.Published data demonstrates the value of utilizing WSI in breast and gynecological pathology. Key issues reported with WSI systems were problems related to focus, resolution and the contrast and brightness of immunohistochemical staining patterns. Grading breast cancer and mitotic count remained challenging in WSI as in conventional microscopy.

Introduction: Newly discovered thyroid nodules in deceased donors are investigated to rule out cancer that can be transmitted, but there are no established protocols. The aim of the study was to compare fine needle aspiration versus intraoperative frozen section in the donor management with limited time. Methods: Data were extracted only from the records of Italian second opinion consultation service in the years 2016 to 2017 and included donor details, pathology diagnoses, complications, transmission risk profile, and impact on transplantation. Results: Among 31 deceased donors with thyroid nodules, we documented 4 with a clinical history of cancer and 27 with a newly discovered nodule. The latter was evaluated by thyroidectomy with frozen section in 22 and fine needle aspiration in 5. Among all donors, 7 had papillary thyroid carcinoma with negligible transmission risk, whereas 8 with unacceptable risk. Two donors presented major bleeding after thyroidectomy, with organ discard in 1 case. Transplantation was delayed in 4 cases that were evaluated with frozen section. Discussion: There was no uniform approach for the investigation of thyroid nodules. Our results showed that fine needle aspiration was more accurate and useful than frozen section. Fine needle aspiration had minor economic impact and a far less rate of bleeding/hemodynamic complications, potentially delaying and compromising organ recovery. Our results suggested considering fine needle aspiration as a first step in the evaluation of thyroid nodules in donors.

The risk of transmission of malignancy from donor to recipient is low. However, this occurrence has dramatic consequences. Many reports of donor-derived cancers in liver transplant recipients have been published, but they have not been systematically summarized into a lucid and unified analysis. The present study is an attempt to provide clarity to this unusual but clinically important problem. We systematically reviewed all patient reports, patient series, and registries published on cancer transmission events through the end of December 2019. We identified a total of 67 publications with 92 transmission events. The most frequently transmitted cancers were lymphomas (30; 32.6%), melanomas (8; 8.7%), and neuroendocrine tumors (8; 8.7%). Most of the melanomas were metastasizing, whereas most of the lymphomas were localized to the graft. The median time to cancer diagnosis after transplantation was 7months, with 78.1% of diagnoses established in the first year. Melanoma carried the worst prognosis, with no recipients alive at 1year after cancer diagnosis. Lymphoma recipients had a better outcome, with more than 75% surviving at 2years. A metastatic cancer carries a worse prognosis for recipients, and recipients with localized cancer can benefit from the chance to undergo transplantation again. The findings confirm the need to pay attention to donors with a history of melanoma but also suggest the need for a more careful evaluation of groups of donors, such as those dying from cerebral hemorrhage. Finally, recipients of organs from donors with cancer should be carefully followed to detect potential transmission.

Oil Red O is a useful tool to assess donor liver steatosis on frozen sections during transplantation. Steatosis is a frequent finding in liver evaluation during transplantation, accounting for 9% to 26% of biopsied donor liver. The degree of macrovesicular steatosis is classified as mild, moderate, and severe; the latter is considered an absolute contraindication to liver transplantation because it is associated with poor allograft outcome. Because of the scarcity of organs, there is a debate whether livers with less severe macrovesicular steatosis are still suitable for transplant. Consequently, tools or methods that allow a more accurate intraoperative assessment of steatosis on frozen sections are mandatory. The aim of this study is to improve intraoperative evaluation of steatosis during transplantation using Oil Red O stain on liver biopsies. Methods Twenty consecutive liver biopsies of donors were collected during transplantation procedures from September 2017 to February 2018 at the Institute of Pathology of the University and Hospital Trust of Verona, Italy. Each liver biopsy was cut at a different thickness (3, 5, and 8 μm) and stained with both Oil Red O and conventional hematoxylin and eosin for intraoperative consultation. The degree (percentage of hepatocytes involved) of fatty changes was recorded. The results obtained during the intraoperative consultation were finally compared with the formalin-fixed and paraffin-embedded permanent section. Results Assessment of steatosis on hematoxylin and eosin frozen sections was reported as mild in 17 cases (85%), moderate in 2 cases (10%) and severe in 1 case (5%). Oil Red O frozen sections reported the following results: mild steatosis in 16 cases (80%), moderate in 2 cases (10%), and severe in 2 cases (10%). The percentage of liver steatosis obtained with Oil Red O was consistent in all cases with that of the permanent sections. The staining procedure for Oil Red O required approximately 18 minutes. Conclusions Oil Red O special stain is a fast and inexpensive tool to improve the assessment of steatosis on frozen biopsies during liver transplantation.

Background Acute kidney injury (AKI) after liver transplantation (LT) is a frequent and serious complication. The incidence of AKI requiring continuous renal replacement therapy (CRRT) ranges from 10% to 30%. Kidney Disease: Improving Global Outcomes guidelines indicate the use of citrate as a locoregional anticoagulant drug for CRRT regardless of the patient's hemorrhagic risk. Despite this indication, however, the use of citrate is still under debate in patients with liver failure and/or LT owing to the potential risk of plasmatic citrate accumulation due to reduced liver clearance. The aim of this study was to evaluate the safety and efficacy of citrate as a locoregional anticoagulation drug in CRRT for AKI after LT. Methods A retrospective analysis was performed in patients with AKI after liver transplantation who were treated with CRRT using citrate as local anticoagulant. Five patients were enrolled from January to December 2015. Results No patients showed complications related to citrate (metabolic acidosis, hyperlactatemia, hypercalcemia, or hypernatremia). All treatments with heparin were stopped owing to circuit clotting. Treatments with citrate was interrupted where it was no longer needed or when other examinations had to be made. None were stopped because of circuit coagulation. Conclusions At our center, 5 patients have been successfully treated with the use of CRRT with citrate for AKI during the post-LT course. Our results, though on a small series of patients, provide evidence that CRRT with citrate can be a safe and promising treatment for AKI after LT.

The 2016 World Health Organization Renal Tumor Classification defines renal oncocytoma (RO) as a benign epithelial tumor; however, malignant histopathologic features have been documented. Rare cases with metastases have been reported. We describe the case of a 62-year-old woman who was referred to the Urology Clinic for a routine work-up. Magnetic resonance imaging and computerized tomography showed a 7-cm mass in the middle and lower portions of the left kidney and 2 suspected liver metastases. The patient underwent surgery. Microscopically both renal and liver lesions presented solid, solid-nested, and microcystic architecture, composed predominantly of large eosinophilic cells without any worrisome pattern except the vascular extension. The cells were positive for S100A1, CD117, and PAX-8 and negative for CAIX, CK7, and AMACR. Fluorescence in situ hybridization showed a disomic profile for the chromosomes 1, 2, 6, 7, 10, 17. No mutation of coding sequence of the SDHB, SDHC, SDHD, VHL, and BHD genes and no loss of heterozygosity at 3p were found. The final diagnosis was "RO" according to the 2016 World Health Organization Renal Tumor Classification with "liver metastases." This report provides a wide clinical-pathologic, immunophenotypical and molecular documentation of a RO with liver metastases.

Guidelines for donor selection have changed to expand the donor pool, considering potential donors affected by a neoplasm. Aim of this retrospective study is to look at the use of organs from donors with a current or history of neoplasm within the Italian Transplant Network. Data, collected and validated by Italian National Health Institute for the time interval 2006–2015, have been reviewed retrospectively by mean of multivariable pivot tables. Donors with neoplasia represented about 5% of all donors, resulting in about 4% of all transplants. Donors presented a benign neoplasm in 29.08% of cases, a malignancy with variable risk of transmission in 69.75% while in 1.34% the nature of neoplasm could not be assessed. Considering all procedures, rate of transmission of a malignancy was 0.03% (10 cases) of all 29858 transplants of the time interval. Notably, cases of transmission were not from donors of this pool, but from donors that, according to our protocols, had no elements of suspect at time of donation. As recipient safety is always the priority and as guidelines have set exclusion criteria for donors with some specific types of malignancy, these results show that use of this type of donors is safe and improve organ pool. Furthermore represent basis for improvement and standardization of donor assessment protocols suggesting that efforts in data collection systems, to produce complete and homogeneous data, are mandatory.

Objectives Liver transplant represents the criterion standard therapy for end-stage liver disease. Biliary complications after liver transplant have shown an increased trend and are characterized by anastomotic and nonanastomotic stenoses. Materials and methods This retrospective single-center observational study included 217 patients who underwent liver transplant between January 2004 and December 2014; 18 patients had anastomotic (8.3%) and 29 (13.4%) had non-anastomotic stenoses. Patients with and without biliary stenosis were compared with regard to their preoperative, intraoperative, and postoperative parameters and donor characteristics. Patients with biliary stenosis were divided into 3 cohorts according to the type of endoscopic treatment performed (single plastic, multiple plastic, and fully covered self-ex-pandable metal stents). We compared the patients with different types of endoscopic biliary drainages for length and type of stenosis, presence of stones, time of onset and treatment, number of procedures, complications, and success rate. Results Preoperative Child-Pugh and Model for End-Stage Liver Disease scores, complication and reoperation rates, and donor age were significantly higher in the stenosis group. We found no statistical differences other than length of stenosis between patients with multiple stents and self-expanding metal stents. Conclusions Preoperative recipient conditions and postoperative morbidities may represent risk factors for development of biliary strictures. Consequently, the optimal endoscopic treatment should be tailored to the type and the onset of stenosis and the patient's condition.

Objective To report a case of primary hepatic pregnancy complicated by acute hemoperitoneum that was treated with a laparoscopic approach. Design Case report and review of the literature. Setting Obstetrics and gynecology unit of a university hospital. Patient(s) A 37-year-old pregnant woman who presented with vaginal bleeding. Intervention(s) Diagnosis by abdominal ultrasound and computed tomography. Main Outcome Measure(s) Patient recovery after minimally invasive laparoscopic surgery and monitoring. Result(s) A hepatic ectopic pregnancy complicated by hemoperitoneum was diagnosed. The hepatic pregnancy was surgically removed via laparoscopy through a retroperitoneal approach, and the patient's human chorionic gonadotropin level was subsequently monitored. The patient's postoperative course was uneventful, and the serum human chorionic gonadotropin level dropped to zero. Conclusion(s) Only 39 cases of hepatic pregnancy have been reported in the literature, making it an exceptional category among abdominal pregnancies. Hepatic localization should be ruled out in cases of unknown pregnancy location. Abdominal ultrasound has a key role detecting hepatic localization and excluding other abdominal implantation sites. Laparoscopic surgery represents a feasible approach for the treatment of first trimester hepatic pregnancies.

BACKGROUND: Assessment of potential liver allograft donors with frozen sections has clinical relevant consequences for the transplant recipient. Several clinical risk factors have been identified that increase the risk of transplantation failure and it is critical for the pathologist to become familiar with the histologic criteria for donor liver suitability. In this setting an accurate and reliable assessment of fibrosis is crucial. We sought to report the value of the rapid chromotrope aniline blue stain (CAB) in a transplantation clinical work-flow for scoring liver fibrosis. MATERIALS AND METHODS: Twenty consecutive intraoperative donor liver biopsy specimens were evaluated by a pathologist at the Transplant Pathology Board Room, AOUI Verona, during 24-hour on-call service. The stage of fibrosis was evaluated according to Ishak score ranging from 0 to 6 (absent to cirrhosis) using hematoxylin and eosin stain (H&E) plus rapid CAB special stain. After a 3-week washout period, only the slides stained with H&E were re-assessed for fibrosis stage by the same pathologist blinded to donor patient data. RESULTS: Combination H&E-CAB staging fibrosis score was higher in 20%, lower in 10%, and the same in 70% of biopsy specimens as determined using only H&E stain alone. Rapid CAB stain takes 20 minutes longer than H&E stain alone. CONCLUSIONS: CAB staining may be performed on frozen tissue from liver biopsy during a transplantation process without a significant delay in diagnosis. Combination H&E-CAB staining improves sensibility of interpretation of fibrosis.

Background: Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines. Methods: A two- step ALERT process was used: ALERT1 consisting of clinical, radiological, and laboratory tests; ALERT2, consisting of intraoperative assessment in suspicious lesions. Results: Four hundred of 506 potential deceased donors entered the ALERT system. Forty- one of 400 (10%) donors were excluded due to unacceptable risk of transmission. Of the remaining 359 193 required histopathology, which excluded malignancy or determined acceptable risk in 161/193 (83%). Thirty- five malignancies were identified: 19 (54%) at ALERT1, four (11%) at ALERT2, nine (26%) picked up at ALERT1 and confirmed by ALERT2. Three (9%) were missed by ALERT and diagnosed at postmortem examination. Prostate (n=12%, 34%) and renal cell (n=7%, 20%) were the most frequent carcinomas. The majority (92%) of prostate adenocarcinomas were of low risk and donation proceeded compared to 43% of renal carcinomas. Four renal carcinomas, two breast carcinomas, and a single case of nine different malignancies excluded donation. Positive ALERT donors had statistically more malignant reports than negative ALERT donors (P=

A 22-year-old Caucasian patient underwent living-donor liver transplantation (LDLT) for hepatic hemangioendothelioma in a healthy liver. The organ donor was his monozygotic twin brother. Surgery was uneventful in both donor and recipient, who received the same postoperative treatment (i.e. no immunosuppression for the recipient). Although both donor and recipient achieved a full liver function recovery, the volume of the recipient's graft increased much more than the donor's residual liver in the first postoperative month (1.6-fold vs. 1.2-fold). This different growth rate correlated with growth hormone (GH)/insulin growth factor (IGF) axis dynamics: the donor had significantly lower insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) values than the recipient on postoperative days (POD) 3-30, although they had similar GH values. Other potential regenerative factors, e.g. tumor necrosis alpha, interleukin 6 (IL-6), insulin and C peptide did not correlate with liver regeneration rate. The particular endocrine picture of the graft may be explained by a modified GH-hepatocyte interaction due to cold ischemia during preservation resulting in a higher IGF production. Whether this is a potential molecular tool by means of which transplanted partial livers promote their regeneration remains to be seen in a larger number of patients.

Background: The use of orthotopic liver transplantation (OLT) for the treatment of patients with hepatocellular carcinoma (HCC) remains controversial because of the risk of both exclusion from the waiting list due to tumor progression and post OLT HCC recurrence. The aim of the present study was to evaluate the effect of an aggressive HCC treatment during the waiting list time on overall and recurrence-free survival of HCC transplanted patients in a single institutional study. Methods: Since 1991, 40 HCC patients joined the OLT-waiting list. Poorly differentiated HCC cases were excluded, while size and number of nodules were not considered as absolute selection criteria. In all, 90% of the study group had HCC treatment while on the waiting list (transarterial chemoembolization, percutaneous therapies, chemotherapy). Results: Only one patient (2.5%) was removed from the waiting list after developing neoplastic portal thrombosis 3 months after listing, while 33 (82.5%) underwent to OLT after a median waiting list time of 11 months (range 3–16 months). On histological examination, 42% of the group did not meet the “Milan criteria” and 42% were pTNM stages III and IV. The median follow-up was 42 months. The 5-year actuarial survival rate was 64% and recurrence-free survival was 91%. HCC recurred in only two patients (6%). Conclusions: The use of routine pre-OLT tumor grading and of an aggressive HCC treatment during the waiting list, in our experience, resulted in a very low risk of pre OLT tumor progression leading to exclusion and of post OLT HCC recurrence.

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.

Background Everolimus (EVE), a mammalian target of rapamycin inhibitor, has been proposed as liver transplant immunosuppressive drug, gaining wide interest also for the treatment of cancer. Although an appropriate tolerance, it may induce several adverse effects, such as fibro-interstitial pneumonitis due to the acquisition of activated myofibroblasts. The exact molecular mechanism associated with epithelial to mesenchymal transition (EMT) may be crucial also in the liver context. This work examines the role and the molecular mediators of EMT in hepatic stellate cell (HSC) and human liver cancer cells (HepG2) and the potential role of EVE to maintain the epithelial phenotype rather than to act as a potential initiators of EMT. Methods Real time-PCR and western blot have been used to assess the capability of EVE at low-therapeutic (10 nM) and high (100 nM) dose to induce an in vitro EMT in HSC and HepG2. Results Biomolecular experiments demonstrated that low concentration of EVE (10 nM) did not modify the gene expression of alpha-smooth muscle actin (α-SMA), Vimentin (VIM), Fibronectin (FN) in both HSC and HepG2 cells, whereas EVE at 100 nM induced a significant over-expression of all the three above-mentioned genes and an increment of α-SMA and FN protein levels. Additionally, 100 nM of EVE induced a significant phosphorylation of AKT and an up-regulation of TGF-β expression in HSC and HepG2 cells. Discussion Our data, although obtained in an in vitro model, revealed, for the first time, that high concentration of EVE may induce EMT in liver cells confirming previous published evidences obtained in renal cells. Additionally, they suggested that mTOR-I should be administered at the lowest dose able to maximize their important and specific therapeutic properties minimizing or avoiding fibrosis-related adverse effects. Conclusions In summary, if confirmed by additional studies, our results could be useful for researchers to standardize new therapeutic immunosuppressive and anticancer drugs protocols.

Patients with severe liver trauma may be referred to liver transplantation (LT), even though no universal algorithm is currently agreed upon. LT is usually performed as a two-stage procedure after failure of primary surgery or in the event of surgery-related acute liver failure (ALF), but pre-transplant patient management, appropriate selection criteria and prompt referral to LT centers are paramount for a favorable graft outcome. This is a report on a patient who underwent LT as a two-stage procedure for sepsis-related ALF after extended right hepatectomy for a complex abdominal blunt trauma. Prompt referral to the Liver Transplant Unit of the Cisanello Hospital, Pisa, where the whole spectrum of surgical options and intensive care support are available was crucial to allow successful LT in a timely fashion. Therefore, the authors strongly advocate the whole algorithm for patients with severe liver traumas be put under control of an experienced LT team in order to improve surgical results.

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.

Background: Alpha-fetoprotein (AFP) messenger RNA (mRNA) in the blood reflects the presence of circulating hepatocellular carcinoma (HCC) cells and is a sensitive marker of HCC extrahepatic metastases. The specificity of this molecular marker and its correlation with the main HCC clinical–pathological parameters remains controversial, however. Methods: AFPmRNA was determined in 50 HCC patients and in 50 patients with diagnosis of cirrhosis (6), or colon (24) or, pancreatic (20) carcinoma. HCC patients with clinically evident extrahepatic metastasis were excluded. HCC diagnosis was confirmed in all patients by histology on percutaneous biopsies or surgical specimens; pathological grading was assessed at the same time. Results: AFPmRNA was positive in 20 HCC patients (40%) and in 18 patients without HCC (36%). The presence of AFPmRNA in the blood correlated significantly with cholestatic indices (p

Introduction. Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. Materials and Methods. From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. Results. The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). Conclusions. Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

To explore the potential prognostic role of preoperative tumor grade and blood AFP mRNA in a cohort of patients with hepatocellular carcinoma (HCC) eligible for radical therapies according to a well-defined treatment algorithm not including nodule size and number as absolute selection criteria.Fifty patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (1) histological assessment of tumor grade by means of percutaneous biopsies; (2) determination of AFP mRNA status in the blood; (3) patient's eligibility for radical therapies.At preoperative evaluation, 54% of the study group had a well-differentiated HCC, 42% had AFP mRNA in the blood, 40% had a tumor larger than 5 cm and 56% had more than one nodule. Surgery (resection or liver transplantation) was performed in 29 patients, while 21 had percutaneous ablation procedures. After a median follow-up of 28 mo, 12-, 24-, and 36-mo survival rates were 78%, 58%, and 51%, respectively. Surgical therapy, performance status and three tumor-related variables (AFP mRNA, HCC grade and gross vascular invasion) resulted as significant survival predictors at univariate analysis. Nodule size and number did not perform as significant prognosticators. Multivariate study selected only surgical therapy and a biologically early HCC profile (AFP mRNA negative and well-differentiated tumor without gross vascular invasion) as independent survival variables.The preoperative determination of tumor grade and blood AFP mRNA status may potentially refine the prognostic evaluation of HCC patients and improve the selection process for radical therapies.