Clinical significance of lens culinaris agglutinin-reactive fraction of serum alpha-fetoprotein in patients with hepatocellular carcinoma.

alpha-fetoprotein (AFP) is an important marker for the diagnosis of hepatocellular carcinoma (HCC) and has been widely used in clinical settings. Recently, the importance of lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) has been indicated. However, the clinical significance of the level of AFP-L3 protein in relation to the characteristics of HCC has not been fully evaluated. In the present study, both the ratio of AFP-L3 (AFP-L3%) and the absolute value of AFP-L3 (AFP-L3-AV) were examined in 80 patients with HCC, and evaluated with respect to characteristics of HCC such as grade of differentiation, size of tumor and morphological findings. Among HCC-specific tumor markers, AFP, AFP-L3% and protein induced in vitamin K absence (PIVKA-II), AFP showed the highest positive rate in patients with HCC, while AFP-L3% showed the lowest rate. AFP-L3% and AFP-L3-AV were, however, most significantly correlated with the grade of HCC differentiation, while AFP showed the least significant correlation. Furthermore, AFP-L3% was most significantly correlated with the size of HCC in patients with solitary HCC. Conversely, neither AFP-L3-AV nor PIVKA-II showed a significant correlation with the size of HCC. In relation to morphological differences of HCC, although AFP-L3%, AFP-L3-AV and PIVKA-II were significantly higher in the diffuse type of HCC than in the nodular type of HCC, AFP was most significantly correlated with the morphological differences of HCC. These results indicate that tumor markers for HCC, such as AFP, AFP-L3%, AFP-L3-AV and PIVKA-II, may play different roles in predicting the characteristics of HCC.     

Permanent interstitial brachytherapy for clinically organ-confined high-grade prostate cancer with a pretreatment PSA < 20 ng/mL

The objective of this study was to determine the effect of biopsy Gleason score 8 and 9 histology on biochemical outcome following a permanent prostate brachytherapy approach that includes multiple periprostatic seeds and supplemental external beam radiation. Forty-six consecutive T1c-T2b (1997 AJCC) patients with Gleason score 8 and 9 prostate cancer who were either hormone naive (33 patients) or received cytoreductive (< or =6 months) hormonal therapy (13 patients) underwent brachytherapy from June 1995 to November 2000. The median patient age was 69.7 years, with a median pretreatment prostate-specific antigen (PSA) of 7.7 ng/mL. The median follow-up was 58 months (range 27-93 months). Forty-five of the patients were implanted with Pd-103 and 44 received supplemental external beam radiation therapy (45 Gy). Biochemical success was defined by either a PSA < or = 0.4 ng/mL after a nadir or by the ASTRO consensus definition. The actuarial 7-year biochemical disease-free survival was 84.8% using either a PSA < or = 0.4 ng/mL or the ASTRO consensus definition. The median postimplant PSA was less than 0.1 ng/mL for both the hormone naive and hormonally manipulated patients. The utilization of hormonal therapy for 6 months or less duration resulted in a statistically nonsignificant improvement in biochemical outcome (92.3% versus 81.8%, P = 0.393). When stratified by pretreatment PSA, 87.9% of patients with a pretreatment PSA < or = 10 ng/mL and 76.9% with a pretreatment PSA > 10 ng/mL (P = 0.377) remained biochemically free of disease. In multivariate analysis, none of the clinical, treatment, or dosimetric parameters predicted for outcome. Following a permanent prostate brachytherapy approach that used multiple periprostatic seeds, the majority of patients with clinically organ-confined Gleason score 8 and 9 prostate cancer remain biochemically free of disease with identical outcomes for both biochemical definitions of success.     

A simultaneous monitoring of Lens culinaris agglutinin A-reactive alpha-fetoprotein and des-gamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients

To elucidate the risk factors for developing hepatocellular carcinoma (HCC) during the follow-up of patients with liver cirrhosis (LC), outpatients with LC were examined periodically by means of serum biochemical assessments, ultrasonography, and computed tomography. Risk factors for HCC were statistically analyzed. We also examined an efficacy of Lens culinaris agglutinin A-reactive profiles of alpha-fetoprotein (AFP-L3%) and des-gamma-carboxy prothrombin (DCP) value using a highly sensitive DCP determination kit (ED036) for the early recognition of HCC. The AFP-L3% and the ED036 value were retrospectively determined with stored serum samples. HCC was diagnosed in 21 of the 78 patients with LC during the follow-up period (mean follow-up period: 42 months). The estimated cumulative incidence of HCC was 25% with 3 years and 48% with 5 years. The most significant risk factor for the development of HCC in LC patients was found to be the mean serum AFP concentration from the year before the HCC detection (p=0.02). At the time of the recognition of HCC, the positive rates of the tumor markers were: serum AFP concentration 14%, serum DCP value 5%, AFP-L3% was 33%, and that of ED036 43%. The positive rate in collaborative use of AFP-L3% and ED036 was 67%. The simultaneous determination of the AFP-L3% and the ED036 value was shown to be effective for the early detection of HCC.     

Long-term androgen deprivation therapy improves survival in prostate cancer patients presenting with prostate-specific antigen levels > 20 ng/mL

PURPOSE: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels > 20 ng/mL. METHODS AND MATERIALS: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level > 20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, < 12 months) or long term (LT-AD, > or = 12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. RESULTS: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). CONCLUSIONS: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level > 20, irrespective of Gleason score or T stage.     

Clinical features of patients who present with metastatic prostate carcinoma and serum prostate-specific antigen (PSA) levels < 10 ng/mL: the "PSA negative" patients

BACKGROUND: Although < 1% of men present with prostate-specific antigen (PSA)-negative prostate carcinoma, in that they have serum PSA levels much lower than the tumor burden would suggest, such patients represent a management dilemma. To the authors' knowledge, little information exists in the literature regarding patterns of disease and response to treatment. The authors wished to define the clinical features of this patient group. METHODS: The British Association of Urological Surgeons Cancer Registry 2000 and 2001 data bases were used to identify the clinical features and outcome of 33 men with metastatic prostate carcinoma who presented with serum PSA levels < 10 ng/mL. Clinical notes and histopathology were reviewed for each patient. RESULTS: Seventeen patients (51%) presented with urinary symptoms and/or pelvic pain, 6% with cachexia and 21% with bone pain. Characteristic bone metastases were present in 81% of patients, similar to the presentation of men with high serum PSA levels. Hypercalcemia was a feature in 9% of patients. Visceral metastases were present in two patients. The median response duration to first-line hormone manipulation was 7 months. No responses were seen in 11 of 13 patients who received second-line hormones or to any third-line treatment. Three of 5 patients who received chemotherapy responded but developed recurrent disease within 8 weeks of treatment cessation. The median overall survival was 12 months. CONCLUSIONS: The presentation of patients with treatment-na?ve PSA-negative metastatic prostate carcinoma is similar to that of patients with high serum PSA levels, but their median survival and response duration to first-line hormone therapy are of much shorter duration. Second-line hormone therapy is ineffective, but early chemotherapy may be beneficial. Hypercalcemia is a particular feature in this group of patients.     

Usefulness of Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) as a marker of distant metastasis from hepatocellular carcinoma

The objective of this study was to clarify the relationship between the serum level of the Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) and the clinical features including sex, age, Child's classification, virus markers, tumour size, tumour stage, distant metastasis, histopathologic findings, portal thrombus and outcome of hepatocellular carcinoma (HCC). We measured the AFP-L3 levels in 170 HCC cases at the time of diagnosis using lectin-affinity electrophoresis followed by antibody-affinity blotting. The patients were divided into two groups, those who were AFP-L3 positive (n=56; AFP-L3 >/=15% relative to the total alpha-fetoprotein (AFP) concentration) and those who were AFP-L3 negative (n=114; AFP-L3 <15%). Then we examined the association between the serum AFP-L3 level and the clinical features of HCC. No significant differences were found in age, sex, and virus markers between the AFP-L3-positive and -negative groups. However, patients in the positive group had worse liver function and larger tumours compared to the negative group. They also had more advanced cancer with poor tumour histology compared to the negative group. Distant metastasis was diagnosed significantly more often in the positive group than that in the negative group. There was no significant correlation between the AFP-L3 level and portal thrombus. Although the follow-up period was brief the prognosis for the positive group clearly was poor. These results suggest that AFP-L3 is a useful indicator of distant metastasis and a poor prognosis for HCC.     

甲胎蛋白异质体在肝癌早期诊断和预警作用研究

目的:探讨甲胎蛋白异质体(AFP-L3)在肝癌的早期诊断价值和对高危人群的预警作用。方法:分别用微量离心柱法和电化学发光法检测176例治疗前原发性肝癌患者和251例慢性肝病患者血清中的AFP-L3和AFP。并对其中的62例慢性肝病患者跟踪随访两年,动态监测AFP-L3。结果:肝癌组的AFP-L3敏感性和中位水平分别为84.09%和16.85,高于良性肝病组(P<0.05)。20相似文献   

Predictive modeling for the presence of prostate carcinoma using clinical, laboratory, and ultrasound parameters in patients with prostate specific antigen levels < or = 10 ng/mL

BACKGROUND: The objective of the current study was to develop a model for predicting the presence of prostate carcinoma using clinical, laboratory, and transrectal ultrasound (TRUS) data. METHODS: Data were collected on 1237 referred men with serum prostate specific antigen (PSA) levels < or = 10 ng/mL who underwent an initial prostate biopsy. Variables analyzed included age, race, family history, referral indication(s), prior vasectomy, digital rectal examination (DRE), PSA level, PSA density (PSAD), and TRUS findings. Twenty percent of the data were reserved randomly for study validation. Logistic regression analysis was performed to estimate the relative risk, 95% confidence interval, and P values. RESULTS: Independent predictors of a positive biopsy result included elevated PSAD, abnormal DRE, hypoechoic TRUS finding, and age 75 years or older. Based on these variables, a predictive nomogram was developed. The sensitivity and specificity of the model were 92% and 24%, respectively, in the validation study for which the predictive probability > or = 10% was used to indicate the presence of prostate carcinoma. The area under the receiver operating characteristic curve (AUC) for the model was 73%, which was significantly higher compared with the prediction based on PSA alone (AUC, 62%). If it was validated externally, then application of this model to the biopsy decision could result in a 24% reduction in unnecessary biopsy procedures, with an overall reduction of 20%. CONCLUSIONS: Incorporation of clinical, laboratory, and TRUS data into a prebiopsy nomogram significantly improved the prediction of prostate carcinoma over the use of individual factors alone. Predictive nomograms may serve as an aid to patient counseling regarding prostate biopsy outcome and to reduce the number of unnecessary biopsy procedures.     

Clinical Value of Hepatoma-Specific Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide and the number 2 cause of cancer mortality in Chi- na.[1] It often develops in cases of liver cirrhosis and chronic hepati- tis. [1-3] Advanced imaging procedures including utrasonograph…     

肝细胞癌根治性切除术后AFP半衰期与复发的相关性研究

目的 探讨BCLC-A期肝细胞癌（hepatocellular  carcinoma,HCC）患者根治性切除术后甲胎蛋白（alpha fetoprotein,AFP）半衰期与HCC复发的关系。方法 对2007年1月至2012年12月行根治性切除术的309例BCLC-A期HCC患者的临床资料进行回顾性分析,将患者分为AFP（+）组和AFP（-）组,比较两组患者术后无瘤生存时间,并对AFP（+）患者术后不同AFP 半衰期组间无瘤生存时间进行分析。结果 AFP（+）组与AFP（-）组的中位无瘤生存时间分别为54.3个月、64.3个月,两者比较差异有统计学意义（P=0.041）。AFP（+）组患者术后AFP半衰期≤5 d和>5 d的中位无瘤生存时间分别为59.1个月、46.2个月,两者比较差异亦有统计学意义（P=0.048）。结论 HCC根治性切除术后AFP（＋）者的预后较AFP（-）者差,术后AFP半衰期≤5 d和>5 d可作为HCC的根治性切除术后复发的预测指标。     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Clinical features and prognosis of hepatocellular carcinoma with reference to serum alpha-fetoprotein levels. Analysis of 606 patients

Clinical features of hepatocellular carcinoma (HCC) with normal serum alpha-fetoprotein (AFP) levels were compared with those of AFP-positive cases. A total of 606 patients were divided into four groups based on their serum AFP levels at the time of diagnosis: group 1 (less than or equal to 20 ng/ml, N = 125), group 2 (20-1000 g/ml, N = 256), group 3 (1000-10000 ng/ml, N = 149), and group 4 (greater than 10000 ng/ml, N = 76). Increasing prevalence of group 1 patients and decreasing prevalence of group 4 were noted during the last 9 years. The proportion of hepatitis B virus-positive cases was significantly lower in group 1 than in group 4. The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio was found to be significantly higher in group 4 than in group 1 regardless of the size of the tumors. The survival rates were compared among the four groups in size matched cases since the size of the tumor significantly influenced their prognosis. The median survival in relatively small HCC patients (less than or equal to 5 cm in diameter, N = 199) were 24.6 months for group 1, 20.6 months for group 2, and 13.7 months for group 3 patients; and those in large HCC (greater than 50% in the proportion of the tumor area, N = 200) were 15.1 months for group 1, 6.3 months for group 2, 5.8 months for group 3, and 5.2 months for group 4. Thus, serum AFP values at the time of presentation are not only of diagnostic value, but also of prognostic significance in patients with HCC.     

Radical prostatectomy for prostate cancer patients with prostate-specific antigen >20 ng/ml

OBJECTIVE: Prostate cancer patients with prostate-specific antigen (PSA) >20 ng/ml are at high risk of progression after radical prostatectomy. Comparison has seldom been made between the outcomes of patients with PSA 20.1-50 ng/ml and those with PSA >50 ng/ml after radical prostatectomy. We retrospectively analyzed the outcomes of these two groups. METHODS: From 1993 to 2002, 60 prostate cancer patients receiving radical prostatectomy were enrolled in this study. Thirty-seven patients with PSA 20.1-50 ng/ml were assigned to Group I. Twenty-three patients with PSA >50 ng/ml were assigned to Group II. Preoperatively, Group II had greater PSA and PSA density than Group I (P < 0.0001). Group II had higher biopsy Gleason score and clinical stage than Group I (P < 0.05). Pathological categories and outcomes of both groups were compared. RESULTS: Group II had higher Gleason score and tumor volume than Group I (P < 0.05). The incidence of organ-confined diseases was 29.7% in Group I and 0% in Group II (P < 0.05). Group II had higher incidence of extracapsular tumor extension, positive surgical margin and lymph node involvement than Group I (P < 0.05). The incidence of postoperative PSA >0.01 ng/ml and PSA failure were higher in Group II than Group I (P < 0.05). Need for adjuvant treatment and death from prostate cancer was similar in both groups. CONCLUSION: Patients with PSA >50 ng/ml had a poorer prognosis than patients with PSA 20.1-50 ng/ml. Those with PSA >50 ng/ml had shorter freedom from PSA failure survivals than those with PSA 20.1-50 ng/ml (P = 0.004). Classification of high-risk prostate patients into two sub-groups with PSA 20.1-50 ng/ml and PSA >50 ng/ml should be considered.     

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT.     

Effect of surgical and chemotherapeutic treatment on alpha-fetoprotein levels in patients with hepatocellular carcinoma.

Quantitative determinations of serum alpha-fetoprotein (AFP) by radioimmunoassay in 193 patients with hepatocellular carcinoma have demonstrated a wide variation in serum levels that appear to be relatively constant for each patient by the time that diagnosis is made. If there is no therapeutic intervention the serum AFP usually follows a gradual increase as the tumor progresses. A few patients have a fall in serum AFP as a preterminal event. Various forms of chemotherapy cause only minor and transient decrease in serum AFP. Surgical resection of tumor produces an immediate fall that parallels the catabolic decay rate for AFP. All AFP-positive patients treated with surgery had recurrence of their tumor with a rise in serum AFP preceeding clinical discovery. The correlation of serum AFP and effective treatment is demonstration of the usefulness of this oncofetal protein marker as an indicator of neoplastic activity for hepatocellular carcinoma and tumors with embryonal cell components and possibly for some other entodermally derived neoplasms.     

Significance of suspicious lesions at transrectal ultrasonography in men with serum prostate-specific antigen levels of < 20 ng/ml

AIMS AND BACKGROUND: The objective of the study was to evaluate the significance of suspicious lesions at transrectal ultrasonography for prostate cancer diagnosis. PATIENTS AND METHODS: A total of 1,009 men with a mean age of 65.0 +/- 7.7 years (range, 40.0-79.0) constituted the study cohort and 265 (26.3%) were diagnosed with prostate cancer on initial biopsy. RESULTS: The cancer detection rate was higher in patients with suspicious lesions (33.2%) than in those with no suspicious lesion (21.5%) (P < 0.001). Pathologic findings of the needle biopsy samples also showed more aggressive characteristics in men with suspicious lesions (P < 0.05). Of 413 men with suspicious lesions, additional lesion-directed biopsies were performed in 133 patients. The positive predictive value of additional lesion-directed biopsy was 18.0%. Of patients who had positive cores on lesion-directed biopsies, all were also found to have positive cores on random biopsies, and no patient had positive cores only on lesion-directed biopsies. The Gleason score was not changed by the findings of lesion-directed biopsies in these patients. CONCLUSIONS: Our findings do not provide a rationale to recommend the addition of lesion-directed biopsy in patients with suspicious lesions at transrectal ultrasonography. However, men with suspicious lesions at transrectal ultrasonography had a higher risk of being diagnosed with prostate cancer.     

肉瘤样肝癌24例临床分析

目的:通过分析各分期肉瘤样肝癌(sarcomatoid hepatocellular carcinoma,SHC)的临床资料、治疗方法及预后,提高临床医生对肉瘤样肝癌的认识。方法:回顾性分析郑州大学第一附属医院2015年1月至2019年12月病理确诊为SHC 24例患者临床资料并随访,男性16例,女性8例。中位发病年龄55岁。结果:临床表现以腹痛、发热为主,肝炎病毒感染者占66.7%,肝硬化者占79.2%。Ⅲ～Ⅳ期占87.5%。平均肿瘤长径6.27 cm。1例行肝移植,8例行手术为主治疗,3例仅进行局部治疗,余进行对症支持、化疗、靶向或联合免疫治疗。入院CT或MRI均有异常表现,活检或术后病理均符合SHC。随访1～39.7个月,中位随访时间4.8个月,术后患者中位总生存期(overall survival,OS)为4.7个月,中位无病生存期(disease-free survival,DFS)为2.3个月。Ⅲ～Ⅳ期患者中位OS为4.8个月。结论:对于Ⅰ期肉瘤样肝癌患者,治疗以外科切除为主,术后给予辅助治疗可使患者受益。对于Ⅲ～Ⅳ期肉瘤样肝癌患者,手术获益局限,可行全身化疗、口服靶向药、...