Primary yolk sac tumor of the cerebellar vermis: case report.

A rare case of yolk sac tumor in the cerebellar vermis is reported. A 2-year-old boy developed headaches, vomiting, and an unsteady gait. Later a tumor was demonstrated in the medial part of the cerebellum by gadolinium-enhanced magnetic resonance imaging (MRI). The tumor was totally removed, and the surgery was followed by chemotherapy. Soon after surgery the elevated alphafetoprotein (AFP) levels in the serum and cerebrospinal fluid were observed to decrease to normal levels. Three months later enhanced MRI showed a lesion in the vermis without any elevation of AFP, and the lesion turned out to be a granuloma. Six months after the second surgery a tumor recurred that could not be totally removed. Cranial radiotherapy was given together with chemotherapy, which resulted in a decrease of AFP to the normal range. The patient is doing well without any elevation in AFP at 1 year 6 months after onset. Related problems in the diagnosis and treatment of yolk sac tumors are discussed.     

Effect of postoperative chemotherapy on the serum alpha-fetoprotein level in hepatoblastoma

Purpose

It is generally accepted that postoperative chemotherapy does not affect the serum alpha-fetoprotein (AFP) level. The authors report on 3 patients who supposedly showed chemotherapy-related changes in their AFP levels after operation.

Methods

This study included 3 patients with hepatoblastoma (1 case of PRETEXT III and 2 cases of PRETEXT IV).

Results

One patient with PRETEXT III underwent a complete tumor resection, and the postoperative AFP level decreased until it reached the normal range. However, he consistently exhibited a transient, 2- to 3-fold increase in the AFP after each course of chemotherapy for 3 courses. The chemotherapy regimen had to be stopped because of drug-induced encephalopathy, but he has been followed up for 5 years without any evidence of recurrence, and his AFP level has also remained stable and in the normal range. Two patients with PRETEXT IV, who underwent a curative tumor resection, also showed similar chemotherapy-related changes in AFP levels. Both of these cases were observed only after the administration of routine postoperative chemotherapy instead of administering further high-dose chemotherapy. The AFP level remained stable for 17 months and 7 months after the cessation of chemotherapy in 2 cases, respectively.

Conclusions

Regarding the postoperative chemotherapy of hepatoblastoma, we have to pay close attention to both the AFP status during chemotherapy as well as the absolute AFP level.     

Assessing Prognostic Significance of Preoperative Alpha-Fetoprotein in Hepatitis B-Associated Hepatocellular Carcinoma: Normal is not the New Normal

Background

Hepatitis B (HBV)-associated hepatocellular carcinoma (HCC) is often associated with alpha-fetoprotein (AFP) production. Although serum AFP has been demonstrated to be a prognostic factor for patient survival, optimal cutoff levels remain unclear.

Methods

Patients with HBV-associated HCC treated by primary liver resection were prospectively followed at a single institution between 1995 and 2008. AFP level was categorized into quintiles for Kaplan–Meier analysis and multivariable Cox proportional hazards regression models.

Results

Best 5-year survival after surgery was observed for patients with AFP in the first quintile (1.4–4.1 ng/mL), with progressively worse outcomes for patients in each increasing quintile. AFP was associated with overall survival (HR = 1.61; 95 % CI 1.30–1.98), disease-free survival (HR = 1.26; 95 % CI 1.10–1.44), and 2-year recurrence (HR = 1.30; 95 % CI 1.07–1.57) in multivariate analysis. Noncirrhotic patients (Ishak 1–5) with AFP in quintile 1 had 94 % 5-year survival, compared with 0 % survival for patients with AFP in quintile 5 (2,332.7–327,560.0 ng/mL) and Ishak stage 6 cirrhosis.

Conclusions

Preoperative serum AFP is an independent predictor of prognosis among HBV-HCC patients following surgical resection. Categorizing AFP into quintiles creates the opportunity to observe differences in outcomes even at low serum levels within the normal range. Additionally, combining AFP quintiles and fibrosis staging provides a predictive model of prognosis for HCC. Thus, even small differences in AFP within the normal range may impact prognosis and disease progression for HBV-HCC.     

A case of renal cell carcinoma producing alpha-fetoprotein

Renal cell carcinoma (RCC) producing alpha-fetoprotein (AFP) is a rare condition with only 11 cases reported in Japan to our knowledge. A 69-year-old man was admitted to our hospital for further examination of an incidental right renal tumor. Laboratory tests showed markedly increased serum level of AFP whereas both HBs antigen and anti-HCV antibody were negative. Computed tomography and magnetic resonance imaging imagings showed a right renal tumor but no tumor in liver, testis or lymph node. We performed right radical nephrectomy. Serum level of AFP declined within the normal range 7 weeks after nephrectomy according to its half-life curve. The tumor specimen was composed mainly of granular cells. Immunohistochemical examination of the tumor cells proved the presence of AFP in the cytoplasm. The possibility of AFP as a tumor marker of renal cell carcinoma in this case was presented.     

The diagnostic value of alpha-fetoprotein in infants and children with teratomas: a questionnaire survey in Japan

Serum alpha-fetoprotein (AFP) values in 61 infants and children with mature, immature, or malignant teratoma were analyzed in comparison with the normal ranges of AFP. AFP was within the normal ranges in 23 of 24 mature teratomas, and higher than the upper border of the normal ranges in 31 of 32 malignant teratomas. The number of immature teratomas studied here was very small. These results suggest that the diagnostic value of AFP would seem very high even in infancy and childhood, if data are compared with the normal ranges. This conclusion appears particularly noticeable because the authors had once made a preliminary report on this subject in which they concluded that the differentiation between benign and malignant teratoma by AFP would be impossible under the age of 2 mo.     

Immunohistochemical localization of alphafoetoprotein in testes of mouse embryos at 17 days of gestation

Immunohistochemistry was used to localize alphafoetoprotein (AFP) in 1 micron plastic sections of embryonic testes in order to investigate the cellular basis of AFP production in murine teratocarcinomas. Atypical germ cells and scattered foci of normal germ cells were AFP-positive in both tumour-susceptible and control animals. AFP could not be demonstrated, however, in tumour stem cells. These results suggest that AFP may be a marker for the endodermal origin of germ cells.     

合并肝硬化中晚期肝癌TACE治疗后血清AFP检测的意义

目的 探讨合并肝硬化的中晚期肝癌患者血清AFP水平对经肝动脉化疗栓塞术（TACE）治疗预后的意义.方法 收集250例TACE术后的中晚期肝癌合并肝硬化患者的血清,采用放射免疫法测定患者血清AFP的水平.将测定的结果分成AFP升高组（＞20 μg/L,n＝165）例和正常组（＜20 μg/L,n＝85）,并对肝癌患者进行随访（1周～65个月,中位时间21.5个月）.用Kaplan-Meier生存曲线分析患者生存率,评估AFP水平及相关因素对中晚期肝癌患者预后的意义.结果 AFP升高组的1、2、5年生存率为57%、48%、5.1%,AFP正常组为37%、46%、12%.AFP升高组的1年生存率明显高于AFP正常组（P＜0.05）,AFP升高组5年生存率明显低于AFP正常组（P＜0.05）.结论 对于中晚期肝癌的患者,血清AFP水平高者较血清AFP水平低者短期预后好,但远期预后差.     

Observations on reliability of commercial assay for alpha-fetoprotein

Thirty patients with nonseminomatous germ cell tumors of the testis were monitored with serum levels of alpha-fetoprotein (AFP). Each patient had at least one AFP determination performed in duplicate: one by the National Institutes of Health (NIH) and one by a commercially available assay. With respect to normal and elevated levels, there was agreement in 60 of the 69 duplicate AFP determinations (87 per cent). Six of the 9 discordant AFP determinations were due to increased sensitivity (a lower normal range) of the NIH assay. There was a close correlation between the quantitative levels of AFP when both the NIH and commercial levels were elevated.     

Early determination of the effect of preoperative TAE by observation of serum AFP changes in patients with hepatocellular carcinoma

Serum Alpha-fetoprotein (AFP) was assessed several times after preoperative TAE on 18 patients with hepatocellular carcinoma, and postoperatively the resected specimens were examined histopathologically. Changes in AFP level after TAE showed five typical patterns: AFP continued to rise in spite of treatment (non-effective type); AFP shows regular and equal increases and decreases (undulating type); AFP showed an increase after initially decreasing (increasing after decreasing type); AFP decreased gradually to normal levels (gradually decreasing type); and AFP decreased along a half-value period line to normal levels (half-value period type). These AFP patterns were intimately related to necrosis rate of tumor and other factors such as tumor size and existence of daughter tumors. Even when the AFP level decreased to 1/2 one week after TAE, the tumor showed only about 70% necrosis. Only when the AFP level fell into 1/4 of the original level after one week we could expect complete necrosis. Immuno-histological findings revealed AFP-producing cells in carcinoma but not in necrotic cells. It seems therefore, that the immuno-histological technique is uneffective in determining the viability of tumor cells.     

Differences in the structure of alpha-fetoprotein and its clinical use in pediatric surgery

Techniques have been studied which distinguish two variants of human alpha-fetoprotein (AFP) on the basis of characteristics of the carbohydrate moiety of this glycoprotein. AFP in serum samples from six children with tumors of yolk sac origin showed little concanavalin-A (Con A) binding. In contrast, Con A binding of AFP was almost complete in serum samples from 14 other subjects with elevated AFP, including two with liver-cell tumors, eight with neonatal cholestasis, and four normal newborn infants. Differences were confirmed by immunoelectrophoretic studies. Thus, AFP from cells of yolk sac origin can be distinguished from AFP from liver cells or from tumors of hepatic cell origin.     

监测AFP变化在原发性肝癌冷冻治疗中的价值初探

目的：探讨监测AFP变化在肝癌冷冻治疗中的价值。方法：分析本院1995年5月-1998年5月术前AFP阳性的原发性肝癌患者62例,其中冷冻治疗24例,观察冷冻治疗前后血清AFP的动态变化。结果：原发性肝癌患者,冷冻治疗术后3d变化不明显,术后半月AFP值基本正常。结论：AFP值的变化在肝癌冷冻治疗中有一定特征,检测AFP值变化可以对肝癌冷冻治疗的疗效和预后作出判断。     

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.     

Alpha-fetoprotein, prealbumin, albumin, alpha-1-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors.

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.     

Resection of liver metastasis from alpha-fetoprotein-producing early gastric cancer: Report of a case

We herein present a case of resected synchronous solitary liver metastasis from alpha-fetoprotein (AFP)-producing early gastric cancer. A 61-year-old woman, who was diagnosed at a routine medical checkup as having early gastric cancer with a liver tumor, came to our hospital for surgery. Her serum AFP level was high at 910ng/ml. An examination was performed to determine whether the liver tumor was primary hepatocellular carcinoma or metastasis from early gastric cancer. She had no evidence of either a hepatitis B or C virus infection, and her liver function was normal. A biopsy specimen from the gastric cancer predominantly revealed moderately differentiated adenocarcinoma, but a focally trabecular pattern compatible with AFP-producing gastric cancer was also observed. Preoperatively, it was concluded that the liver tumor was metastasis from an AFP-producing early gastric cancer. We thus performed distal gastrectomy and a posterior segmentectomy of the liver. Her serum AFP level decreased to the normal range within 2 weeks after the operation. An immunohistological examination revealed that AFP-positive cells were present in both the gastric cancer and liver tumor. One year after the operation, there was no sign of recurrence.     

A case of mediastinal non seminomatous germ cell tumor successfully treated with chemotherapy and curative surgery

A 15-year-old male was admitted to our hospital because of left lateral chest pain. Chest XP and CT scan revealed a huge anterior mediastinal mass (13 x 8 x 12 cm). The serum AFP level was raised (8,089 ng/ml). Examination of a percutaneous biopsy of the tumor suggested non-seminomatous germ cell carcinoma. After three courses of chemotherapy with CDDP, Bleomycin and VP-16, the mass reduced in size and the serum AFP level decreased to the normal range. The tumor was completely removed. The postoperative course was uneventful and he has had no recurrence for 10 months following the operation. AFP is a very useful parameter for deciding the timing for an operation.     

Induction chemotherapy and radical resection for primary nonseminomatous mediastinal germ cell tumor (NSGCT); report of a case

A 15-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor. The tumor was visualized by chest radiography 3 months prior to admission. Computed tomography (CT) revealed a heterogeneous solid tumor located in the anterior mediastinum. Although CT-guided needle biopsy had been performed twice, histologic diagnosis could not be confirmed. We believed this tumor to be nonseminomatous mediastinal germ cell tumor (NSGCT) and started intensive chemotherapy with cisplatin (CDDP) without histologic diagnosis because his serum AFP level was rapidly increasing. After 2 courses of chemotherapy, his serum AFP level returned to the normal range and surgical resection of the tumor with part of right lung was performed. Histopathological examination revealed that the tumor consisted of mature teratoma and yolk sac tumor. He underwent 1 course of chemotherapy post-operatively because a small number of viable cells were histopathologically recognized in the yolk sac component. At the time of writing, the patient is alive without any evidence of recurrence.     

Changes in anterior fontanel pressure in preterm neonates receiving isoflurane, halothane, fentanyl, or ketamine

The effects of anesthetics on intracranial pressure (ICP) may be different in preterm neonates than in adults because the neonate's cranial sutures are not yet fused. The authors monitored changes in anterior fontanel pressure (AFP), a noninvasive indicator of ICP, during anesthesia in 44 preterm neonates without neurologic disease. Atropine, 0.02 mg/kg, and pancuronium, 0.1 mg/kg, were given intravenously to all patients, who were ventilated with oxygen and air. Anterior fontanel pressure was monitored and recorded continuously with a Ladd AFP monitor. Systolic blood pressure (SAP) and mean blood pressure (MAP) were recorded at 1-min intervals. After a 5-min control period of stable AFP, each of the four groups of 11 patients then received either 0.75% isoflurane, 0.5% halothane, 20 micrograms/kg fentanyl, or 2 mg/kg ketamine. Anterior fontanel pressure decreased 11% during isoflurane administration, 9% during halothane administration, 10% after fentanyl, and 10% after ketamine. These changes were statistically significant, but clinically mild, and AFP remained within the normal range. Statistically significant decreases in SAP and MAP occurred during isoflurane and halothane administration, but not after fentanyl or ketamine. The authors conclude that indirectly measured ICP decreases slightly in preterm neonates without neurologic disease after administration of the anesthetics studied. The difference between these results and those of studies of ICP in adults is presumably due to the compliance of the neonate's open-sutured cranium.     

Yolk sac tumor of the anterior mediastinum and pulmonary metastases; report of a case

A 31-year-old female was clinically diagnosed as having a anterior mediastinal yolk sac tumor because of the elevation of the AFP (17,500 ng/ml), a large mass lesion (9 x 5 cm) in the anterior mediastinum and bilateral lung metastases. After 4 courses of chemotherapy with cisplatin (CDDP), etoposide (VP-16) and bleomycin hydrochloride (BLM), the mediastinal mass reduced in size significantly and the serum AFP level reached within normal range. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a weak uptake in the mediastinum, accordingly the operation was performed. The tumor was completely removed and there were no viable foci of the tumor in part of the tumor. After the operation, 4 courses of chemotherapy with carboplatin (CBDCA), VP-16 and ifosfamide (IFM) were performed. She is alive without evidence of recurrence in 5 months after operation. It was noticed that the serum AFP is a useful indicator for determing the chance of operation after chemotherapy.     

Lectin-reactive alpha-fetoprotein as a marker for testicular tumor activity

BACKGROUND: Lens culinaris agglutin (LCA)-affinity electrophoresis resolves serum alpha-fetoprotein (AFP) into three isoforms, AFP-L1, -L2 and -L3. The ratio of AFP-L3 to total AFP (AFP-L3%) is frequently high in hepatocellular carcinoma (HCC) patients, and thus, it is widely used for early diagnosis of HCC. In the present study, we used the subfraction profile of LCA-binding AFP to diagnose and monitor testicular tumor activity. METHODS: Serum samples were collected from 21 testicular tumor patients, and the LCA-reactive fractions were determined by LCA-affinity electrophoresis coupled with antibody-affinity blotting. The histological diagnosis was non-seminomatous germ cell tumor (NSGCT) in 15 patients and pure seminoma in six patients. RESULTS: Serum AFP levels were abnormally elevated (>20 ng/mL) in 10 of 15 NSGCT patients. One NSGCT patient and two seminoma patients showed borderline AFP levels between 10 and 20 ng/mL. LCA-reactive AFP was detected in all 11 NSGCT patients with serum AFP levels above 10 ng/mL, but not in the two seminoma patients with serum AFP levels above 10 ng/mL. In testicular tumor patients, the broad band of AFP-L2 could not be completely separated from AFP-L3. The mean ratio of AFP-L3 plus AFP-L2 (AFP-L2 + 3%) was as high as 94% (range 80-99%) in these patients. Serial determinations of LCA-reactive fractions were performed in eight of the 11 LCA-reactive AFP-positive patients. They included five patients who received chemotherapy, and three patients who underwent orchiectomy for stage I NSGCT. In three of eight patients, LCA-reactive AFP was detected even after normalization of total AFP levels. All three patients relapsed, with elevation of serum AFP within several months. CONCLUSION: Determination of LCA-reactive AFP might be a useful marker for testicular tumor activity in patients with lower AFP levels.     

Impact of Preoperative α-Fetoprotein Level on Disease-Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Background

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Methods

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10?ng/ml) and increased-level group (>10?ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10–150, 150–500, and ≥500?ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Results

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4?%, respectively, for those with normal AFP; 57 and 10?%, respectively, for those with AFP 10–150?ng/ml; 46 and 24?%, respectively, for those with AFP 150–500?ng/ml; and 28 and 62?%, respectively, for those with AFP ≥500?ng/ml.

Conclusions

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.