Symptomatic Hepatocellular Carcinoma Research Articles

Canadian Cancer Trials Group HE.1: A phase III study of palliative radiotherapy for symptomatic hepatocellular carcinoma and liver metastases.

LBA492 Purpose: To determine if more patients (pts) with painful liver cancer have improved pain 1 month following radiation therapy (RT), compared to best supportive care (BSC). Methods: This multi-centre, phase III trial randomized pts with painful hepatocellular carcinoma (HCC) or liver metastases (LM) 1:1 to BSC alone or with single fraction RT (8 Gy). Eligible pts had end-stage disease unsuitable for local, regional or systemic therapies, > 4 weeks since chemotherapy or TACE, > 2 weeks since targeted therapy or immunotherapy, and no planned systemic therapy. The primary objective was to determine if the proportion of pts with improved liver cancer pain "intensity at worst" on Brief Pain Inventory (BPI) by ≥2 points from baseline to 1 month was higher following RT vs. BSC alone. Secondary endpoints included proportion of pts 1) alive at 3 months, 2) with improvement ≥2 points in BPI at 1 and 3 months, 3) with a 25% reduction in opioids at 1 month and 4) with improved quality of life (QOL): Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) hepatobiliary subscale (HBS) change score ≥5 and Trial Outcome Index ≥7 at 1 month. Results: Sixty-six pts were randomized, 43 with LM (12 colorectal, 5 breast, 4 pancreas, 3 lung, 19 other), 23 with HCC. 59% had ECOG performance status 2 or 3, 64% Child Pugh (CP) score A vs. 36% CP B or C. The clinical target volume irradiated was the whole liver or near whole liver (median 2013 cc). Forty-two pts (24 on RT and 18 on BSC) completed baseline and 1-month assessments. The average baseline pain at worst score was 7/10. A significant improvement in the primary endpoint, ‘worst’ pain score on BPI, from baseline to 1 month was seen in 67% of pts on RT and 22% on BSC (p = 0.004). The proportion of pts with improved ‘worst’ pain at 1 month, with no increase in opioid use was 21% on RT vs 0% with BSC (p = 0.07). From baseline to 1 month, the proportion of pts with a significant improvement in BPI “pain at its least” was higher for pts on RT vs. BSC (63% vs. 28%, p = 0.03), as was BPI “percentage relief in pain by treatment” (59% vs. 25%, p = 0.04). A sensitivity analysis of all pts, treating those with no 1 month assessment as having ‘no improvement’, found improvements in BPI ‘worst’ pain in 49% of pts on RT and 12% for BSC alone (p = 0.002). Eleven patients on the BSC arm crossed over to receive RT at 1 month. A trend to improvement in FACT HBS post RT vs BSC was seen at 1 month (p = 0.07), with no statistically significant difference in other FACT-Hep subscales. The proportion of pts with grade ≥2 AE (CTCAEv4.0) at day 30 was 58% on RT vs 33% on BSC (p = 0.05). Grade ≥3 AE were uncommon. There was a trend for improved 3 month survival with RT (51% vs. 33% for BSC alone, p = 0.07). Conclusions: Single fraction RT (8 Gy) improves hepatic pain in the majority of patients with end-stage HCC or liver metastases, with a trend to improved survival. This research is funded by the Canadian Cancer Society (Grant #703547). Clinical trial information: NCT02511522 .

Paraneoplastic syndrome frequency and prognostic effect in hepatocellular carcinoma patients.

Symptomatic hepatocellular carcinoma (HCC) patients may generally display constitutional symptoms such as abdominal pain, weight loss, anorexia and localized mass, or atypical clinical features of paraneoplastic syndrome (PNS) such as hypercholesterolemia, hypercalcemia, hypoglycemia, erythrocytosis and thrombocytosis. The most common PNS in HCC is hypercholesterolemia, hypercalcemia, hypoglycemia and erythrocytosis. The aim of this study isto evaluate the relationship of PNS in HCC patients. In this study, the data of 534 patients who were followed up with the diagnosis of HCC between January 2010 and December 2020 in the Gastroenterology clinic were evaluated retrospectively. Clinical data, age, gender, complete blood count of patients with and without PNS, liver biochemistry, alpha-fetoprotein (AFP) level, hepatitis B surface antigen, anti-hepatitis B virus, Child-Pugh score, model for end-stage liver disease score, tumor volume, portal vein thrombosis, liver biopsy histology and radiologic images were taken from the hospital data system and analyzed. Out of the 534 HCC patients, 120 (22.3%) were PNS-positive patients. There was a significant difference between the ages of PNS-positive and PNS-negative patients, and PNS-positive patients were older (64.60±12.97) (P=0.02). PNS-positive HCC was determined as hypoglycemia 5.8%, hypercalcemia 6.3%, erythrocytosis 3.9%, hypercholesterolemia 2.4% and thrombocytosis 3.9%. AFP level (22908 ± 60 ng/ml) and tumor diameter (>10 cm) were higher in the PNS-positive group. Multivariate analysis showed that stage C according to Child-Pugh score and tumor diameter >10 cm were independent predictors of poor prognosis, whereas PNS erythrocytosis and thrombocytosis were independent predictors of better prognosis. In PNS-positive HCC patients, hypoglycemia and hypercalcemia were associated with poor prognosis according to Child-Pugh score, whereas erythrocytosis and thrombocytosis were associated with good prognosis.

Impact of baseline and concomitant corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy.

531 Background: The impact of corticosteroid treatment (CT) on the efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) is undefined. We evaluated whether CT administered at baseline (bCT) or concurrently to ICI (cCT) influences clinical outcomes of HCC patients treated with ICI. Methods: This retrospective, multi-center observational study was conducted across 9 tertiary academic referral centers collected 341 HCC patients who received ICI across 3 continents between January 1, 2016 and April 1, 2019. Outcome measures included overall (OS) and progression-free survival (PFS) calculated from time of ICI commencement and overall response rates (ORR) defined by Response Evaluation Criteria in Solid Tumors (v1.1) on 6-8 weekly periodic restaging. Results: Of 331 eligible patients, 254 (76%) had BCLC-C stage HCC and received mostly PD(L)-1 ICI monotherapy (n=250, 85%). Median OS was 12.1 months (95%CI 9.2-15.0 months) and median PFS was 8.1 months (95%CI 6.3-10 months). In total 81 patients (24%) received >10 mg prednisone equivalent daily either as bCT (n=15, 4%) or cCT (n=66, 20%). Indications for CT included procedure/prophylaxis (n=37, 45%), management of irAE (n=31, 37%), cancer-related symptoms (n=5, 2%) or comorbidities (n=8, 3%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in uni- and multi-variable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (2.4 vs. 11.3 months, p=0.01), OS (4.5 vs. 12.8 months, p=0.05) and reduced ORR (p=0.03) compared to cancer-unrelated indications. Conclusions: This is the first study to demonstrate that neither bCT nor cCT appear to influence response and OS following ICI in HCC. Worse survival and ORR in CT recipients for cancer-related indications appears driven by the poor prognosis associated with symptomatic HCC.

Palliative External Beam Radiation Therapy for Hepatocellular Carcinoma With Right Atrial Tumor Thrombus

Hepatocellular carcinoma (HCC) with right atrial (RA) tumor thrombus via progression through hepatic veins into the inferior vena cava is a challenging entity with limited treatment options. We describe a case of a patient with a symptomatic HCC RA tumor thrombus who achieved a durable and effective symptomatic response to palliative radiotherapy. We also report our institution's experience treating 10 HCC patients with RA tumor thrombus with palliative radiotherapy to a median biological effective dose (α/β = 10) of 50.6 Gy (range, 29.3-71.2 Gy). Median follow-up was 5 months. Palliative radiotherapy was well-tolerated, with no grade ≥ 3 acute toxicities. Only one patient experienced in-field progression. Seven patients were alive at least 3 months following radiotherapy, and median overall survival was 5 months (range, 3-15 months). This unique series suggests HCC RA tumor thrombus-directed radiotherapy may offer safe palliation and can be considered to improve patients' quality of life.

Serum miRNAs as predictive and preventive biomarker for pre-clinical hepatocellular carcinoma

The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6–12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using α-fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations.

TIE2-expressing monocytes: a possible cellular diagnostic and prognostic biomarker for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and the third leading cause of cancer-related deaths worldwide (1). Major risk factors for HCC include chronic infection by hepatitis B virus (HBV) or hepatitis C virus (HCV) and alcoholic liver cirrhosis. Advanced and symptomatic HCC disease is not amenable to curative surgery, therefore screening programs for high-risk populations are implemented to increase early detection and effective surgical treatment of HCC (2). However, a definitive diagnosis of HCC requires concordant findings from several invasive and non-invasive diagnostic parameters, including liver biopsy, serum alpha-fetoprotein (AFP) levels, computed tomography, or magnetic resonance imaging (2). Nevertheless, noninvasive imaging is not sufficiently sensible for detecting an early-stage HCC, similarly AFP has low sensitivity and specificity to be used as a screening biomarker (3). In this framework, effective biomarkers for the early detection as well the progression of HCC are greatly needed. Matsubara et al. in Hepatology (4) described the possible significance of circulating CD14+CD16+ monocytes expressing Tyrosine kinase with Ig and EGF homology domains 2 (TIE2) [TIE2-expressing monocytes (TEMs)] as biomarkers for the detection of both early- and late-stage HCC. Indeed, TIE2 is mainly expressed on endothelial cells and binds all the known angiopoietins (ANGs) and TEMs are peripheral as well as tumor-infiltrating myeloid cells presumed to be characterized by a profound pro-angiogenic activity (5-7). In particular, TEMs have been reported in tumors of the kidney, colon, pancreas and lung, as well as in soft tissue sarcomas (7) where angiogenesis is known to be important for tumor progression. In this framework, HCC is a highly vascularized tumor, the progression of early lesions to overt HCC is strongly associated with increase of vasculature (8,9) and the antiangiogenic drug, sorafenib prolongs to a certain extent survival of patients with advanced HCC. Matsubara et al. (4) report on the frequency of circulating TEMs in a cohort of 168 HCV-infected patients, of which 89 were with HCC. The investigators found that the frequency of TEMs was significantly higher in patients with HCC than HCV-infected patients without HCC or healthy subjects. No difference was found among HCC patients at different stages of the disease, thus establishing TEMs as a stage-independent, diagnostic biomarker for HCC. In addition, higher blood TEM levels correlate to a worse recurrence-free survival after HCC resection or radiofrequency ablation (RFA) therapy, suggesting a role for TEMs also as prognostic biomarker. Furthermore, they also identified TEMs in HCC tumor lesions preferentially localized in perivascular tumor areas correlating with increased microvessel density in the tumors. Therefore, it’s possibly suggesting that HCC-infiltrating TEMs are proangiogenic. Moreover, high circulating and intratumoral TEM levels correlate with a more advanced Child-Pugh stage, suggesting that TEM frequency correlates positively with the degree of liver inflammation/stage of cirrhosis and negatively with liver function. The biology underlying TEM’s involvement in human tumor angiogenesis and progression is essentially unknown and several questions need to be addressed in order to possibly improve HCC anti-angiogenetic therapy. Indeed, the proangiogenic activity exerted by TEMs in HCC may represent one of the reasons for the limited efficacy of sorafenib or other antiangiogenic treatments. Furthermore, elevated circulating levels of the TIE2 ligand, ANG2, correlate with a worse prognosis in untreated HCC patients and predict shorter survival in HCC patients treated with Sorafenib (10). The study by Matsubara et al. (4) is the first to present evidence suggesting that circulating TEMs may be a diagnostic biomarker for both early- and late-stage HCC, although they are not strictly peculiar of HCC but detectable also in other tumors (5,7). These very interesting findings need to be validated on a larger scale of HCC patients to confirm the relevance of TEMs as diagnostic/prognostic marker for HCC as well as therapeutic target for improving the efficacy of current treatments for HCC.

Phase II Trial of Palliative Radiation Therapy for Symptomatic Hepatocellular Carcinoma and Liver Metastases

superior to those in Group A (48.5%, 32.4%), but no significant difference was observed. The 1and 2-year OSs were 75.9% and 36.9% in Group A, 75.0% and 58.3% in Group B, and 81.0% and 52.3% in Group C. These 2year survival rates were superior to previously reported data after conventional irradiation with TMZ in EORTC-NCIC trial. Five-year OS of patients in Group B (29.2%) was superior to that in Group C (2.8%). As for the adverse events, there was no significant difference in RNFSs. The 1and 2-year SNFSs in Group B (92.3%, 61.5%) were better than those in Group A (82.5%, 41.3%) and in Group C (67.1%, 23.5%). Group B showed 2.7-fold lower risk for necrosis in SVZ in compared with Group C, although the statistical significance was not proven (p Z 0.122). Conclusions: In MGMT-Met cases, reduction of treatment dose demonstrated the same effect on local control, but the same risk for in-field necrosis. This reduced-dose IMRT (48 Gy/8Fx.) showed tendency to decrease the risk for necrosis in SVZ and it might result in increased rates of long survivor. However, the effective dose delivery to target while avoiding the dose for SVZ was still difficult even with IMRT and further consideration of the fractionation scheme was required. Author Disclosure: T. Iuchi: None. K. Hatano: None. H. Kageyama: None. T. Imagunbai: None. T. Kodama: None. N. Tohyama: None. S. Yokoi: None. T. Sakaida: None. K. Kawasaki: None. Y. Hasegawa: None.

Surveillance for Hepatocellular Carcinoma: Long Way to Achieve Effectiveness

Surveillance for hepatocellular carcinoma (HCC) in high risk groups including those with cirrhosis as well as with chronic HBV infection is recommended by several practice guidelines including those by the Asian Pacific Association for the Study of Liver (APASL) [1], the American Association for the Study of Liver Disease (AASLD) and the European Association for Study of The Liver (EASL). The evidence supporting the surveillance recommendations in these guidelines is based on evidence of intermediate strength, although arguably the evidence is strongest for HCC surveillance in individuals infected with HBV in Southeast Asia. For example, two randomized controlled trials were conducted in China among individuals with chronic HBV infection with and without cirrhosis. In one placebo-controlled randomized study of nearly 19,000 HBV-infected patients, it was shown that HCC surveillance with both abdominal ultrasound and serum AFP repeated at 6-month intervals resulted in a 37 % reduction in HCCrelated mortality [2]. However, the other randomized controlled trial of 5,581 HBV-infected patients reported that serum AFP repeated at 6-month intervals did not result in a significant reduction in overall mortality [3]. The latter study was smaller and had detected HCC less frequently than the first study and therefore could have suffered from a lack of adequate statistical power. In addition to these two randomized trials, a population-based surveillance program using serum AFP every 6-months among HBVinfected patients in Alaska reported that, during a 16-year follow-up period, patients with HCC who received surveillance had significantly longer 5-year survival compared with historical controls (42 vs. 0 %, respectively) [4]. Last in the evidence hierarchy, several nonrandomized trials and observational cohort and case–control studies have reported that patients who undergo HCC surveillance are diagnosed at an earlier stage of HCC, are more likely to receive potentially curative therapy, and have a significant reduction in cancer-specific mortality compared with patients detected with symptomatic HCC [5, 6]. The ‘‘efficacy’’ of HCC surveillance reflects the degree to which surveillance produces the expected result under controlled conditions chosen to maximize the likelihood of observing an effect if it exists. By contrast, ‘‘effectiveness’’ addresses the extent to which HCC surveillance is beneficial when deployed in medical practice settings [7]. Effectiveness takes into account external factors such as individual patient characteristics, health system features, and societal influences. For HCC surveillance to be effective, several steps need to be enacted. These include (1) identification of high risk patients who are appropriate for surveillance (HBV and HCV with advanced fibrosis/ cirrhosis), (2) availability and accessibility of HCC surveillance to patients at risk in appropriate health care settings, (3) recommendation of the intervention by health care providers, (4) acceptance of HCC surveillance by patients, (5) adherence to surveillance, recall and follow-up at the recommended intervals, the benefits of therapy, (6) availability of appropriate diagnostic test follow-up for abnormal surveillance, and (7) availability of efficacious curative or palliative treatment once HCC is diagnosed. Given the multiplicity of components involved with determining HCC surveillance effectiveness, one could assess the interactions between these factors to arrive with an estimate of how one particular intervention would H. B. El-Serag (&) Dan L Duncan Professor of Medicine, Michael E DeBakey VA Medical Center, Houston Center for Quality of Care and Utilization Studies, Baylor College of Medicine, Houston, TX, USA e-mail: hasheme@bcm.edu

Dysphagia from Hepatocellular Carcinoma Metastases to the Esophagus Occurring Post-Liver Transplantation

Purpose: Introduction: Hepatocellular carcinoma (HCC) commonly metastasizes to the lungs, lymph nodes, musculoskeletal system and adrenal glands. Metastasis to the esophagus has been reported on rare occasions, though the diagnosis is usually made at autopsy. Esophageal metastases of HCC are thought to occur through tumor invasion into the portal system with subsequently dissemination. We present a rare case of symptomatic HCC metastasis to the esophagus occurring post-liver transplantation. Case: A 71 year-old male was referred after evaluation of abnormal liver tests revealed an alpha-fetoprotein of 4,271 and a 6.5 cm mass in right lobe of liver suspicious for HCC. There was no personal or family history of liver disease or HCC, there was no weight loss or history of variceal bleeding, and examination revealed no signs of decompensated liver disease. He was not a candidate for partial hepatectomy because the non-tumor part of the liver appeared cirrhotic on imaging. He underwent extended-criteria orthotopic liver transplantation about three weeks after his initial consultation. Explant pathology revealed moderately-well differentiated HCC in right lobe with small tumor nodules in left lobe. Surgical margins were positive for HCC at the portal vein and inferior vena cava margins. The non-neoplastic liver showed minimal steatosis and fibrosis. Post-transplant course was complicated by liver abscess eventually requiring re-transplantation, abdominal pain after t-tube removal, and ERCP without obvious bile leak but with abnormal nodules seen in distal esophagus. He also developed nausea and dysphagia to solids. EGD revealed multiple pedunculated, ulcerated lesions in mid-distal esophagus, each 1–2.5 cm in size occurring alongside of varicosed veins. Biopsied were consistent with HCC. Discussion: Pre-mortem diagnosis of HCC metastases to the esophagus is extremely rare, but has been reported to occur similarly to our patient with clinical presenting symptoms of dysphagia and findings of pedunculated lesions in the esophagus. Our patient was at high risk for HCC recurrence or metastasis given the positive surgical margins. We believe this is the first reported case of pre-mortem diagnosis of HCC metastasis to the esophagus post liver transplantation.

Resectability rate of hepatocellular carcinoma in rural southern Africans.

The purpose of this analysis was to ascertain the resectability rate of symptomatic hepatocellular carcinoma in rural southern African black males. All 224 such patients proven to have hepatocellular carcinoma in a single hospital were included in the study. Of 205 patients undergoing a complete diagnostic work-up, 134 [65.3 per cent) were judged on clinical criteria to be inoperable, 23 (11.2 per cent) had pulmonary or osseous metastases, and 38 (18.5 per cent) proved on hepatic imaging and 5 (2.4 per cent) on hepatic arteriography to have an irresectable tumour. Thus, only five (2.4 per cent) of these patients proceeded to laparotomy. Another 7 patients who did not have an arteriogram, 9 with surgical emergencies, and 2 mistakenly believed to have an amoebic hepatic abscess also underwent laparotomy. Only 2 patients (0.9 per cent of 223) proved to have a resectable tumour. The extremely low resectability rate reinforces the urgent need for a surveillance programme to detect early tumours in high-risk members of this population.

The surveillance and diagnosis of hepatocellular carcinoma

The increasing incidence of hepatocellular carcinoma (HCC) is becoming a considerable problem in Europe. While no national surveillance programme exists, there is increasing evidence that surveillance programmes are efficacious and may be cost-effective. The prognosis of large, symptomatic HCC is poor and only palliative treatment is available. In contrast small tumours are now amenable to several modes of treatment including liver transplantation, surgical resection and loco-regional ablation with acceptable 5 year survival rates. Therefore, the identification of small lesions through screening should prolong survival. Consequently, the European Association for the Study of the Liver (EASL) has recommended surveillance with ultrasound scans and tests for alpha fetoprotein every 6 months. Screening is now routine clinical practice in many parts of the developed world.

Magnetic resonance imaging of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy, usually develops in patients with cirrhosis, growing sequentially from low-grade dysplastic nodules to frank malignant HCC. Its recognition is critical because curative treatment and prognosis require early diagnosis. Survival in patients with HCC relates directly to the number, size, and extent of lesions at diagnosis. Imaging of HCC is complicated because the tumor has a varied imaging appearance and frequently coexists with other cirrhotic nodules. Magnetic resonance imaging (MRI), the best available diagnostic technique, offers good contrast resolution and diagnostic sensitivity ranging from 33% to 77%. The main difficulty is not in diagnosing large tumors, but rather small tumors (<2 cm), because of considerable overlap on imaging between benign (regenerative), borderline (dysplastic), and malignant nodules. Increasing degrees of histological malignancy are associated with increasing arterialization and loss of portal blood supply; therefore, recognition of HCC requires dynamic imaging with gadolinium-enhanced T1-weighted sequence. Typically, HCC is a focal lesion with high signal intensity on T2-weighted images, variable signal intensity on T1-weighted images, intense arterial phase enhancement after gadolinium injection, and isointensity or hypointensity at the portal venous phase. The sensitivity of MRI for detecting small lesions is low, and improvement is still needed. Newer contrast agents, higher field strength (3 Tesla) imaging, and perfusion and diffusion MRI techniques possibly will provide greater sensitivity and specificity for detecting small HCCs in the future.

Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience.

The prognosis for patients with hepatocellular carcinoma (HCC) is poor because of the low chance of curative treatment. To increase the chance of intervention and to improve survival, early detection of subclinical HCC (SCHCC) by alpha-fetoprotein (AFP) and/or ultrasonography (USG) screening is implemented in many countries. Three hundred six Chinese patients with HCC diagnosed between January 1995 and December 1997 were recruited. They were categorized into two groups: 142 patients (group 1) had SCHCC diagnosed by screening (AFP and/or USG), and 164 patients (group 2) presented with symptomatic HCC. The tumor size was significantly smaller in group 1 compared with that of group 2 (3.5 cm vs. 8.1 cm; P <.0001). A significantly higher proportion of patients had bilobar involvement, multifocal HCC, diffuse-type HCC, portal vein infiltration, and distant metastasis in group 2 when compared with group 1. Operability and feasibility of treatment by transcatheter intra-arterial chemoembolization (TACE) in group 1 patients (26.8% and 45.1%, respectively) were significantly better than in group 2 patients (7.9% and 32.3%, P <.0001 and P =.03, respectively). The cumulative survival rate was significantly higher in group 1 than in group 2 (P <.0001). For those who had surgical resection and those who had TACE, group 1 patients had a higher cumulative survival rate compared with that of group 2 patients (P =.04 and P =.0003, respectively). Screening for HCC by AFP and/or USG can identify tumors at an early stage, resulting in a higher chance of receiving treatment. Whether it can improve survival requires a further prospective, randomized study.

Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma

The objective of this study was to evaluate the indications for percutaneous ethanol injection (PEI) performed in a single session under general anesthesia for treating patients with cirrhosis and large (tumors > 5 cm) hepatocellular carcinoma (HCC), and relevant survival curves. Between November 1991 and November 1996, 108 patients were treated (a total of 128 procedures). They fell into 3 groups: 24 patients with single, encapsulated HCC measuring from 5-8.5 cm (Group A); 63 patients with single, infiltrating HCC measuring from 5-10 cm or multiple HCC (Group B); and 21 patients with advanced disease, either hepatic (Child's Class C) or neoplastic (symptomatic HCC or with portal thrombosis) type (Group C). The mean amount of ethanol injected was 62 mL. The average hospital stay was 3.8 days. The mean follow-up time was 40 months. The 1-, 2-, 3-, and 4-year survival rates were: 72%, 65%, 57%, and 44%, respectively, for Group A; 73%, 60%, 42%, and 18%, respectively, for Group B; and 46%, 25%, and 0%, respectively, for Group C. Mortality was 0.7% (bleeding from esophageal varices in a Child's Class C patient). The rate of major complications was 4.6% (1 case of peritoneal hemorrhage, 1 case of severe liver failure, 1 case of transient renal insufficiency, 1 case of peritoneal seeding, and 2 cases of infarctions of a segment adjacent to the tumor). Single session PEI has been proven to be a valid alternative in patients otherwise treated surgically or with transcatheter arterial chemoembolization who present with adverse prognostic factors or risks for these therapies, and may be an option for selected patients with advanced disease previously excluded from any therapy. Risk conditions are marked portal or pulmonary hypertension or esophageal varices at risk of bleeding, superficial tumors with severe coagulation disorders, hyperfibrinolysis, chronic renal insufficiency, and obstructive jaundice.

Microwave tissue coagulator in liver resection for cirrhotic patients.

The use of the microwave tissue coagulator was studied on 20 consecutive elective hepatic resections carried out for symptomatic hepatocellular carcinoma with liver cirrhosis. The mean operative blood loss (excluding one patient with hepatic vein injury) was 1132 mL. Five patients required no blood transfusion. The average time taken to coagulate the anticipated liver transection plane was less than 15 min. Apart from the complications similar to those occurring in hepatic resections for cirrhotic patients, higher incidences of intra-abdominal sepsis (20%), sympathetic pleural effusion in the absence of chest or intra-abdominal sepsis (20%), and persistent fever lasting more than 1 week (40%) were encountered. It was considered that these complications were related to the coagulated tissue present in the liver remnants (mean depth of tissue coagulation = 3.8 mm) and concluded that although the hospital mortality rate of 10% and the mean operative blood loss of 1132 mL were acceptably low, microwave liver surgery carried a high morbidity rate which is a drawback in major hepatic resectional surgery.

Differential lectin reactivities of α-fetoprotein in hepatocellular carcinoma: Diagnostic value when serum α-fetoprotein levels are slightly raised

The specificity and sensitivity of alpha-fetoprotein (AFP) binding to Concanavalin-A (Con-A) and Lens culinaris agglutinin (LCA) in 26 South African blacks with advanced symptomatic hepatocellular carcinoma (HCC) but only slightly raised serum AFP concentrations (20-500 ng/mL) was compared with that in patients with similar serum AFP levels from diseases that might be mistaken clinically for HCC (seven 'benign' liver disease [BLD] patients and six with metastatic liver disease [MLD] from gastrointestinal tumours). Con-A-Sepharose-4B affinity chromatography did not differentiate between the different groups: fucosylation rations for the HCC patients were 0.81 +/- 0.60, compared with 0.63 +/- 0.27 and 0.54 +/- 0.32 in patients with BLD and MLD, respectively. Electrophoresis of AFP serum and fraction in the presence or absence of Con-A and LCA showed an increase in the AFP C2 band. Rank correlation analysis of the AFP L2 and L3 bands combined could distinguish between patients with HCC and other hepatic diseases (P less than 0.05).

Subclinical hepatocellular carcinoma in Hong Kong Chinese.

Of the 208 Chinese patients with histologically proven hepatocellular carcinoma (HCC) seen during a 5-year period, 191 patients presented with symptomatic HCC and 17 patients with asymptomatic HCC (subclinical HCC, SCHCC) being picked up by alpha-fetoprotein (AFP) screening. Compared with the patients with symptomatic HCC, patients with SCHCC had a better performance status (p less than 0.01), higher serum albumin levels (p less than 0.05) and lower alkaline phosphatase levels (p less than 0.01). In those patients with symptomatic HCC, 4.7% were operable and only 2 patients had a tumour diameter of less than 5 cm. In contrast, patients with SCHCC had a higher operability rate (76.5%, p less than 0.0001) and all had a tumour of less than 5 cm in diameter (p less than 0.0001). Patients with SCHCC, most of whom had their tumour resected, had a better long-term survival (p less than 0.0001). We conclude that patients with SCHCC picked up by AFP serosurveillance have a better performance status, higher operability and better prognosis.