Surveillance Study for Clinical Stage I Testicular Seminomas and Nonseminomatous Germ Cell Tumors

Background: Optimal therapy for stage I testicular tumors is still controversial. This study evaluated the efficacy of a surveillance policy for patients with testicular stage I seminomas and nonseminomatous germ cell tumors (NSGCT).
Methods: From 1984 to 1996, 24 patients with stage I semi noma and 20 with stage I NSGCT were fol lowed after radical orchiectomy with tumor markers and imaging studies. All patients were followed for at least 2 years except for those who recurred within 2 years. Recurrent patients were treated with cisplatin-based chemotherapy.
Results: The median follow-up periods for seminoma and NSGCT patients were 41 and 54 months, respectively. Recurrences were detected in 2 seminoma (8.3%) and 10 NSGCT (50%) patients. Eleven of the 1 2 recurrent patients (92%) were detected within 2 years after orchiectomy. The seminoma patients both recurred in the retroperitoneal lymph nodes, while 70% of the NSGCT patients recurred in the lung and/or retroperitoneal lymph nodes. The recurrent seminoma patients were treated with chemotherapy and are alive without disease for 1 7 and 24 months after orchiectomy. One NSGCT patient died of cancer, but the other 9 recurrent NSGCT patients are alive without disease at 25 to 11 3 months after orchiectomy.
Conclusions: Surveillance alone is reliable for monitoring patients with stage I testicular seminoma and NSGCT. The majority of recurrences occurred within 2 years, necessitating intensive follow-up for 3 years. As the lung metastatic rates in NSGCT patients were high, a more accurate assessment for lung metastasis is desirable in these patients.     

Treatment of seventy-eight patients with testicular tumors

Seventy-eight patients with testicular tumors were treated in our clinic between April, 1972 and October, 1990. The average age of patients with seminoma (37.5 yrs) was higher than that (24.5 yrs) of those with non-seminomatous germ cell tumor (NSGCT). Histopathologically, 34 patients had seminoma and 36 patients had NSGCT. The remaining 8 patients had non-germinal cell tumors. The 5-year survival rate was 76.7%, 90.3% and 75.8% for all patients, seminoma group and NSGCT group, respectively. As for seminoma group, the 5-year survival rate was 100%, 50.0% and 33.3% for Stage I, Stage IIb and Stage III, respectively. The survival rate of Stage IIb and Stage III in seminoma group were lower than Stage I statistically. In NSGCT group, the 5-year survival rate was 100% for Stage I and 26.7% for Stage III, between the two groups there was significant difference. The higher serum LDH and HCG levels, the lower the survival rate in NSGCT. Serum AFP, beta-HCG levels and ESR were unrelated to the survival rate. The survival rate for the patients treated by the chemotherapy including CDDP was compared to those treated by the other therapy in germ cell tumor (greater than or equal to Stage IIb). The survival rate of CDDP group was higher than the others (p less than 0.01).     

Two cases of testicular tumors with high alpha-fetoprotein levels: a case report

Two patients with testicular tumors whose serum alpha-fetoprotein (AFP) persisted to show an abnormally high concentration are reported. Case 1 : A 42-year-old male who had been suffering from chronic hepatitis, underwent left high orchiectomy for a left testicular tumor in 1998. Diagnosis was an authentic stage I seminoma. In 2002, chemotherapy was performed for a metastatic seminoma revealed as a solitary mass in the mediastinum by radiographic studies, and histologically confirmed to be a metastatic seminoma. Although lymph nodes were gradually reduced in size, the serum AFP and transaminase levels remained at an abnormally high concentration. The subfraction profile with lens culinaris hemagglutinin (LCA) revealed elevation of only peak 1 which implied that the chronic hepatitis was due to liver dysfunction. After a 10-month follow-up the levels of both AFP and transaminase decreased, and the patient was disease-free. Case 2: In 2002, a 30-year-old male underwent left high orchiectomy for a left testicular tumor, and histological examination revealed seminoma, immature and mature teratoma, embryonal carcinoma. The serum AFP was elevated to 45 ng/ml. Diagnosis was authentic stage I. After 2 courses of chemotherapy, the serum AFP remained at an abnormally high concentration. However, there were no new lesions. The serum AFP level was not elevated in any of the family members. The subfraction profile with LCA revealed elevation of only peak 1, which implied that there were no viable lesions. After a 24-month follow-up AFP was about 20 ng/ml and the patient was disease-free.     

甲胎蛋白异质体3、异常凝血酶原、甲胎蛋白检测肝细胞癌的对照研究

目的分析3种肿瘤标志物甲胎蛋白异质体(AFP-L3)、异常凝血酶原(DCP)、甲胎蛋白(AFP)单独或联合检测肝细胞癌(HCC)的临床意义。方法分别用电化学发光法检测AFP,ELISA法检测AFP-L3、DCP,利用受试者工作特征曲线(ROC曲线)分析3种标志物单独和联合检测肝细胞癌(随机组和AFP阴性组)的敏感性、特异性、曲线下面积、阳性预测值和阴性预测值。比较肝细胞癌组与健康对照组和疾病对照组的AFP-L3、DCP、AFP水平的差异。分析治疗前AFP阴性肝细胞癌病例联合检测AFP-L3、DCP的意义。结果①单独检测肝细胞癌病例的3种肿瘤标志物,AFP-L3的敏感性、特异性分别是48.7%、97.7%;DCP的敏感性、特异性分别是42.5%、98.4%;AFP的敏感性、特异性分别是68.7%、94.6%。联合检测AFP-L3、DCP和AFP,敏感性、特异性分别是87.5%、92.2%。②肝细胞癌随机组的AFP-L3、DCP、AFP水平与健康对照组和疾病组比较差异有高度统计学意义(P0.01)。③AFP阴性肝细胞癌组的AFP和AFP-L3水平与肝良性疾病组比较差异无统计学意义,但DCP水平差异有统计学意义(P0.05)。结论 AFP-L3、DCP与AFP单独检测时AFP的敏感性最高,而DCP的特异性最高,是区分肝硬化与AFP阴性的肝细胞癌血清学的良好指标。AFP-L3、DCP与AFP的联合检测能提高肝细胞癌血清学检测的敏感性和特异性,在肝细胞癌诊断方面比目前大多数传统的组合方法更优胜、更准确。     

HLA-antigen distribution in seminoma,HCG-positive seminoma and non-seminomatous tumours of the testis

Summary Histocompatibility antigens play a certain role in the development of testicular tumours. 151 patients with testicular cancer (86 non-seminomatous germ cell tumours—NSGCT-and 65 pure seminoma) were typed for the HLA-antigens of the A, B, C and DR locus. 24 patients of the pure seminoma group and 50 patients of the NSGCT group had an elevated serum HCG level preoperatively. The antigen DR-5 was elevated in the seminoma group whereas the incidence of B-13 was increased in the NSGCT group. In terms of antigen distribution HCG-positive seminoma resembles seminomatous tumours rather than NSGCT.     

睾丸肿瘤87例临床分析

目的:提高睾丸肿瘤的诊治水平。方法:对87例睾丸肿瘤患者临床资料进行分析。结果:经手术和病理诊断,生殖细胞肿瘤79例,占睾丸肿瘤的90.1%;其中精原细胞瘤44例,占生殖细胞肿瘤的55.7%;良性肿瘤7例,占睾丸肿瘤的8.1%。非精原细胞性生殖细胞瘤(NSGCT)发病集中在5岁以下和18~40岁;精原细胞瘤发病集中在18岁之后;5~17岁仅1例发生睾丸肿瘤。精原细胞瘤和NSGCT患者3、5年生存率分别为90.6%、81.3%和83.3%、56.7%。结论:①睾丸肿瘤多为生殖细胞肿瘤;②NSGCT发病集中在5岁以下和18~40岁两个年龄段;③精原细胞瘤很少在17岁之前发病;④5~17岁很少有睾丸肿瘤发生;⑤精原细胞瘤3、5年存活率较NSGCT高。     

Intrahepatic cholangiocarcinoma detected by elevated levels of alpha-fetoprotein-L3 after hepatectomy for hepatocellular carcinoma in a patient with Budd-Chiari syndrome

We report the case of a 57-year-old woman with Budd-Chiari syndrome, hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC). She underwent partial hepatectomy for HCC in April 2000. After surgery, alpha-fetoprotein (AFP) and protein induced by vitamin K absence II (PIVKA-II) returned to normal levels, but lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) increased, and ultrasonography showed a nodule 2 cm in greatest dimension in the left lateral segment of the liver. We diagnosed this nodule as recurrence from HCC and performed a partial hepatectomy in October 2001. Microscopic examination showed that tubular adenocarcinoma and immunohistochemical staining was focally positive for AFP. AFP-L3 was 0% and AFP was 5 ng/ml 3 months after re-operation. This case was interesting in that ICC was detected by elevated levels of AFP-L3, and ICC produced AFP from the time it was minute in size.     

甲胎蛋白异质体3含量对早期肝癌的预后价值

目的 探讨甲胎蛋白异质体3(lentil lectin-reactive alpha-fetoprotein-L3,AFP-L3)的含量对早期肝癌的预后价值.方法 97例早期肝癌患者根据术前AFP和AFP-13的含量分为:(1)AFP阳性、AFP-L3阴性组(29例):AFP＞20 μg/L & AFP-13＜15%;(2)AFP-L3、AFP均低含量组(16例):15%≤AFP-L3≤50% & 20 μg/L≤AFP≤200 μg/L;(3)AFP-L3、AFP均高含量组(13例):AFP-L3＞50% & AFP＞200 μg/L;(4)AFP-L3高含量、AFP低含量组(24例):AFP-13＞50%& 20 μg/L≤AFP≤200 μg/L;(5)AFP-L3低含量、AFP高含量组(15例):15%≤AFP-L3≤50% & AFP＞200 μg/L.对各组患者的肿瘤分化程度、术后1、2、3年生存率和无瘤生存率进行分析.结果 AFP-13阴性患者的肿瘤分化程度、术后3年生存率和无瘤牛存率明显优于AFP-L3阳性患者(χ2=21.051,10.043,4.450,6.977,25.566,P＜0.05).AFP-L3高含量组患者的肿瘤分化程度、术后1、2、3年生存率和无瘤生存率明显低于低含量组(χ2=7.938,3.488,9.085,P＜0.05).结论 AFP-L3含量的增高提示肿瘤恶性程度高,预后不良,尤其是AFP水平低时.手术前后检测AFP-L3含量对于患者预后的评价具有指导意义.     

Competing Risks Analysis of Predictors of Delisting Owing to Tumor Progression in Liver Transplant Candidates with Hepatocellular Carcinoma

Orthotopic liver transplantation (OLT) is potentially curative for patients with early stage hepatocellular carcinoma (HCC). However, tumor progression before OLT remains a problem. Ninety-three patients were listed for transplantation with HCC or diagnosed with HCC following listing between March, 1997 and September, 2001. Modified TNM Stage was I/II in 82 patients and III in 11 patients. Seventy-one patients (76%) were transplanted with a median waiting time of 3.4 months, and 22 (24%) patients were delisted owing to tumor progression (14), noncompliance (5), and death from liver failure (3). Using a cox model competing risks approach, higher baseline alpha-fetoprotein (AFP) >or= 100 ng/mL was the only factor independently associated with a higher hazard rate of delisting owing to tumor progression (p = 0.00003), whereas four separate factors were independently associated with a lower hazard rate of transplantation: more recent listing year (1999-2001, p = 0.010), blood type O (p = 0.013), Stage I HCC (p = 0.029), and serum bilirubin < 4 mg/dL (p = 0.032). By logistic regression, AFP >/= 100 ng/mL was the only factor that significantly influenced the probability of delisting owing to tumor progression (p = 0.001). In conclusion, the initial AFP level may be useful along with tumor stage in defining an urgency score for liver transplant candidates with HCC.     

Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-β in testicular tumor patients

BACKGROUND: Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG-beta frequently produce discrepancies, that is when hCG or hCG-beta is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG-beta in testicular tumors. METHODS: Simultaneous determination of hCG and hCG-beta was performed in 54 patients with testicular seminoma and 74 with non-seminomatous testicular tumors. RESULTS: For detection of seminoma patients, hCG-beta was more effective than hCG because hCG-beta was positive in 83% (45/54) of the patients and hCG was positive in 50% (27/54). In non-seminomatous testicular tumor cases, hCG-beta was positive in 74% (55/74) and hCG was positive in 82% (61/74). The cases of hCG<1.0 mIU/mL and HCG-beta>0.1 ng/mL were significantly more frequently seen in patients with seminoma than in those with non-seminomatous testicular tumor (P < 0.001). Fourteen patients had recurrent tumor. At recurrence, only hCG was elevated in nine cases, only hCG-beta was elevated in two cases and both in one case. For diagnosis of falsely positive hCG, testosterone administration was effective because after testosterone administration, serum hCG levels became undetectable (< 1.0 mIU/mL) within one week in three examined cases. CONCLUSION: Human chorionic gonadotropin-beta was a better marker of seminoma than hCG. For earlier detection of recurrence, both markers should be examined. For diagnosis of falsely positive hCG, testosterone administration was effective.     

Testicular tumor in Down syndrome

A 33-year-old male patient with Down syndrome, who stayed in a welfare institution, visited our hospital due to left testicular enlargement. He was diagnosed as having a left testicular tumor and underwent radical inguinal orchiectomy. Preoperatively, serum level of beta-human chorionic gonadotrophin (beta-HCG) increased to 0.9 ng/mL (normal range <0.2 ng/mL). For the last 2 years after orchiectomy, the serum level of beta-HCG remained normal. Histopathological examination of specimen revealed a typical seminoma. It is currently thought that risk of developing leukemia in patients with Down syndrome is 20- to 30-fold higher than that in normal subjects. Furthermore, the incidence of testicular cancer as a complication other than leukemia is expected to increase because of the increasing postpubertal population with Down syndrome.     

Clinical parameters that predict histology of postchemotherapy retroperitoneal lymph node mass in testicular cancer

BACKGROUND: Since the advent of cisplatin-based chemotherapy, the majority of metastatic testicular cancers can be cured by chemotherapy followed by retroperitoneal lymph node dissection (RPLND). However, postchemotherapy RPLND confers no therapeutic benefit if the residual mass contains no viable cells. Therefore, to determine which parameters predict a patient's likelihood of having only necrosis in the residual mass, we retrospectively analyzed clinical parameters of patients who underwent postchemotherapy RPLND. METHODS: Data from 27 patients with metastatic testicular cancer were analyzed. The histology of the primary tumor was seminoma in 11 cases and non-seminoma in 16 cases. All of the patients with non-seminoma showed a normalization of tumor markers after chemotherapy. Analysis of clinical parameters included data for the initial histology, pretreatment tumor marker levels, postchemotherapy retroperitoneal mass size, and the histology of the dissected RPLNs. RESULTS: Histological examination of dissected RPLNs showed residual tumor in 27% of seminoma patients and 38% of non-seminoma patients. In seminoma patients, no viable cells were found in all six patients with pretreatment lactate dehydrogenase (LDH) levels below 7.5 times the upper limit of normal, or in all five of the patients with postchemotherapy RPLNs less than 2.5 cm. In non-seminoma patients, no viable cells were found in nine of 10 patients with pretreatment alpha-fetoprotein (AFP) levels less than 2700 ng/mL, or in eight of nine patients with residual mass less than 2.5 cm. CONCLUSIONS: Both postchemotherapy RPLN mass size and pretreatment tumor marker levels are possible predictors for necrosis of the residual mass in testicular cancer patients.     

Serum CA19-9 levels in testicular germ cell tumor patients

This study was designed to examine whether measurement of serum CA19-9 was useful in testicular germ cell tumor patients. We analyzed the clinical courses of 55 testicular germ cell tumor cases diagnosed after high orchiectomy. The patients in this study consisted of 33 seminomas and 22 non-seminomatous germ cell tumors (NSGCT), and their mean age was 32.7 +/- 12.7 years (mean +/- SD). The mean follow-up period after the operation was 33.7 months. The positive rate of the pre-treatment serum CA19-9 level was 16.4% (3.0% in seminomas versus 36.4% in NSGCT, p = 0.0017). The pre-treatment serum CA19-9 levels in NSGCT patients were significantly higher than those in seminoma patients (46.6 +/- 50.0 U/ml versus 10.6 +/- 9.6 U/ml, p = 0.0008). We divided the patients into two groups according to the detailed histological types, and found that the serum CA19-9 levels in the patients with embryonal carcinoma (EC) were significantly higher than in those without EC (p = 0.0160), and the levels in those with yolk sac tumor (YS) were higher than in those without YS (p = 0.0099). Moreover, the levels in those with either EC or YS were significantly higher than in those with neither EC nor YS (p = 0.0004). In 9 patients with a high serum pre-treatment CA19-9 level, the serum CA19-9 level was useful as a monitoring marker through the treatment or tumor progression. On the other hand, the pre-treatment serum CA19-9 level did not correlate with the clinical stage or prognosis. In conclusion, the phenomenon that the serum levels of CA19-9 increase in testicular germ cell tumor patients is not extremely rare, and in NSGCT, especially in EC or YS, the serum CA19-9 can be a useful tumor marker.     

Liver transplantation for patients with hepatocellular carcinoma

BACKGROUND: Liver transplantation (LT) has been advocated as a salvage treatment for unresectable hepatocellular carcinoma (HCC). Selection criteria still need to be developed in Taiwan. OBJECTIVES: The purpose of our study was to assess the clinical findings and outcome of cirrhotic patients with HCC undergoing liver transplantation. METHODS: Our study consisted of 13 HCC patients who underwent liver transplantation during October 1996 to March 2003. The medical records and pathologic reports were analyzed retrospectively. RESULTS: Overall survival rates at 1 and 3 years were 86% and 61%, respectively. HCC recurrences occurred in three patients, one of whom is still alive with HCC recurrence 2 years after LT. The other two patients died of HCC recurrence 1 and 2 years after LT, respectively. Pretransplant alpha-fetoprotein (AFP) levels of >200 ng/mL were noted in all three patients with HCC recurrence. In contrast, only one of the ten patients without HCC recurrence had pretransplant AFP >200 ng/mL (P = .003). Four patients did not meet Milan criteria, two of whom had HCC recurrence. However, the other two patients with microscopic vascular invasion survived and were free of HCC. The only one patient, who had histologic grade 4 HCC, died of recurrence, although his tumor was AJCC stage 1. CONCLUSIONS: High AFP level is a risk factor for HCC recurrence after LT. In addition to Milan criteria, histologic tumor grading should be considered in patient selection. Microscopic vascular invasion may not affect the outcome of the patients with early HCC.     

Analysis of the Risk Factors of Untransplantable Recurrence After Primary Curative Resection for Patients with Hepatocellular Carcinoma

Purpose

To determine the prognostic factors that predict recurrence of hepatocellular carcinoma (HCC) exceeding the University of California at San Francisco (UCSF) criteria after primary resection.

Methods

HCC patients who underwent curative liver resections between 2001 and 2007 and who were within the UCSF criteria (n = 716) were examined. Independent prognostic factors were examined by the Cox proportional hazard model.

Results

A total of 285 patients (39.8 %) developed recurrences. Of the patients who developed recurrences, 180 had HCC still within the UCSF criteria (63.2 %), and 105 developed HCC beyond this criteria (36.8 %). Among the population with primary transplantable HCC, patients with larger primary tumor sizes, serum α-fetoprotein (AFP) levels over 400 ng/mL, satellite nodules, vascular invasion, or undifferentiated HCC had a risk of untransplantable recurrence, as shown by univariate analysis. In multivariate analysis, undifferentiated HCC and vascular invasion were identified as the significant predictors with adjusted hazard ratios of 9.25 [95 % confidence interval (CI) 2.13–40.21] and 2.19 (95 % CI 1.34–3.58), respectively. When only preoperative factors were considered in multivariate analysis, primary tumor size and serum AFP levels over 400 ng/mL were identified as significant predictors with adjusted hazard ratios of 1.24 (95 % CI 1.07–1.45) and 1.72 (95 % CI 1.05–2.82), respectively.

Conclusions

For primary HCC patients within the UCSF criteria, larger tumor sizes and AFP levels over 400 ng/mL were associated with postresection recurrence of HCC exceeding the UCSF criteria. Because these are clearly markers for aggressive tumor biology, whether early primary transplant will alter the aggressive tumor behaviors warrant further investigation.     

肿瘤标志物在肝细胞癌合并门静脉癌栓诊断中的意义

目的:分析肿瘤标志物在肝细胞癌合并门静脉癌栓诊断中的意义.方法:回顾性分析1993年1月-2011年1月经影像学诊断为肝细胞癌并门静脉癌栓患者475例,同时随机选取同期经影像学诊断为肝细胞癌的手术患者977例.将甲胎蛋白(AFP)、癌胚抗原(CEA)、CA125作为实验因素.结果:2组一般情况差异无统计学意义(P＞0.05). ROC分析结果显示AFP、CA125的AUC面积分别达到0.814、0.783,AFP诊断界数值为32.91 ng/mL,CA125为113.65 U/mL.两者并联敏感性为0.909,特异性为0.410;串联时敏感性为0.520,特异性为0.970.当肝细胞癌患者满足AFP≥20 000 ng/mL时,其诊断敏感性为0.24,特异性为0.96,准确性为0.73,筛检阳性率0.76.结论:在检测肝细胞癌合并门静脉癌栓中尚无敏感性和特异性均令人满意的肿瘤标志物,AFP和CA125水平的检测对临床实践中判断是否合并门静脉癌栓有一定的指导意义.     

Radioimmunologic serum determinations of alpha-fetoprotein in patients with tumors of the testis (author's transl)]

Alpha-fetoprotein (AEP) serum levels were determined by a new radioimmunoassay (sensitivity about 5 ng/ml) in 47 patients with teratocarcinoma of the testis and in 58 cases with seminoma before operation and during the postoperative course of the disease. In 140 healthy adult persons normal AFP levels below 15 ng/ml were measured. Of 14 preoperative cases with teratocarcinoma, 12 (86%) showed pathologic AFP levels over 20 ng/ml up to 3875 ng/ml. Postoperatively, cases free of metastases developed normal AFP concentrations within 4 to 10 weeks, whereas cases with distant metastases retained constant or increasing pathologic levels following a clinical deterioration. Only in three postoperative cases were Ouchterlony-positive results (AFP sensitivity about 10 000 ng/ml) observed. In contrast, patients with seminoma showed normal AFP levels below 20 ng/ml pre- and postoperatively. According to the results, AFP radioimmunoassay is recommended as an important tool for the differentiation of teratocarcinoma from other tumors of the testis and as a useful parameter for the control of therapy and the course of the disease.     

Significance of serum ferritin level in testicular tumors]

The clinical value of serum ferritin level in patients with testicular cancer was studied. Seven cases of seminoma and nine cases of non-seminoma from 1983 to 1989 were evaluated. The serum levels of ferritin, human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) were estimated before and after treatment. Abnormally high values of serum ferritin before treatment were noted in 4/7 (57%) in seminoma, 3/9 (33%) in non-seminoma and 7/16 (44%) in total. The total rate showing abnormally high values of serum ferritin was lower than that of beta-HCG and LDH. Meanwhile it was the same as that of AFP and higher than that of CEA. Changes in the serum ferritin level did not always correspond with the clinical course. In 3 out of 6 tumor free patients, higher levels of serum ferritin before treatment became normal after treatment. In one patient with a high level of serum ferritin before treatment, the level of serum ferritin remained higher and retroperitoneal lymph node metastasis developed after treatment. In 9 cases with normal serum ferritin level, 7 showed the normal range of ferritin level throughout the treatment course. These findings suggests that in some patients with testicular cancer, the serum ferritin level might serve as a tumor marker indicating the efficacy of the treatment and the tumor recurrence.