Normal Alpha-fetoprotein Levels Research Articles

Treatment of Growing Teratoma Syndrome

To the Editor: Growing teratoma syndrome consists of an enlarging mature teratoma arising during or after chemotherapy for a nonseminomatous germ-cell tumor, with normal serum levels of alpha-fetoprotein and human chorionic gonadotropin.1 The preferred treatment is complete surgical resection2 because teratomas are resistant to chemotherapy and radiation therapy. Although embryonal carcinomas express little or no retinoblastoma protein (pRB),3 mature teratomas express high levels of pRB. Normally, cyclin-dependent kinase 4/6 (CDK4/6) stimulates cell growth by phosphorylating pRB. The development of selective CDK inhibitors,4 including PD0332991 (Pfizer), which selectively inhibits CDK4/6, suggests a new treatment for growing teratoma syndrome. We report on . . .

Long-term outcome for men with teratoma found at postchemotherapy retroperitoneal lymph node dissection

Patients with pure teratoma within the postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen traditionally have been considered at low risk for disease progression. The objectives of this study were to determine the disease-related outcomes of patients who had pure teratoma identified at the time of PC-RPLND and to examine the prognostic value of clinical variables that were identified previously as important predictors of disease recurrence in these patients. Between 1980 and 2003, 97 patients with metastatic nonseminomatous germ cell tumor and pure teratoma histology at the time of PC-RPLND were identified. The medical records of these patients were reviewed retrospectively for pertinent clinical and treatment-related outcomes. At a median follow-up of 7.4 years, 21 patients (22%) developed recurrent disease after PC-RPLND. The 5-year and 10-year probabilities (+/-standard error) of freedom from disease recurrence were 81%+/-4% and 76%+/-5%, respectively. The postchemotherapy alpha-fetoprotein (AFP) level and mediastinal involvement at presentation were statistically significant predictors of disease recurrence on multivariate analysis. Nine of 97 patients (9.3%) died from testis cancer, and 4 patients died from other causes. In patients with pure teratoma histology at PC-RPLND, mediastinal involvement at presentation and the presence of an elevated AFP level before PC-RPLND predicted an unfavorable outcome. The absence of mediastinal involvement and normal AFP level, however, did not confirm freedom from disease recurrence. Patients who had teratoma at the time of PC-RPLND remained at considerable risk for disease progression because of the unpredictable nature of teratoma and the presence of unrecognized, active germ cell disease outside the retroperitoneum.

UNDULANT COURSE OF AFP: A Sign of Tumor Activation or Not?

Objective: To assess the predictive value of undulant alpha fetoprotein (AFP) course in recurrence of germ cell tumors (GCT). Patients/method: A retrospective file search of 491 patients with GCT was performed and 18 patients who had an undulant course of AFP levels (increased and spontaneously decreased) without any demonstrable tumor on radiological images were selected for the study. Results: The median age of the 10 boys and 8 girls was 2 years (1.1–16 years). All the patients were disease-free for a median of 16.2 months (8.4–132 months). At follow-up, radiologically proven tumor recurrences were diagnosed in 8 patients in median 12.2 ± 3.2 months from the initial diagnosis (8.4–18.2 months) and 7.4 ± 2.2 months from the last normal level of AFP (5.0–11.2 months). The mean peak AFP values within the first 90 days were 24 ± 38.1 ng/mL and 11.1 ± 10.9 ng/mL in patients who did and did not have recurrent disease, respectively (p =. 0051). The patients whose AFP levels were higher than 10 ng/mL were likely to have recurrent disease (p =. 02). Conclusion: Without a demonstrable tumor, the small amplitude undulations may only require careful follow-up. However, it should be kept in mind that despite the decrease in AFP levels, there still might be a risk of recurrence, especially in patients who have greater amplitude undulations.

Epidemiology and Survival of Hepatocellular Carcinoma in Turkey: Outcome of Multicenter Study

Hepatocellular cancer (HCC) is one of the important health problems in Turkey. We aimed to determine the clinical and demographic features of HCC in the Turkish population and to evaluate the prognostic and survival features. Two hundred and twenty-one patients with HCC from five hospitals in Turkey are included in this study. In 44.4% of the 221 patients with hepatitis B virus and in 21.3% of the 221 patients with hepatitis C virus were found to be responsible for HCC etiology. It has been shown that HCC developed on cirrhosis basis in 74.2% of the patients. HCC was presented with single solitary nodule in 69.2% of the patients. Non-liver metastasis was present in 12.5% of the patients. In 21.7% of the patients, alpha-fetoprotein (AFP) levels were above the diagnostics level of 400 ng/ml. The median overall survival (OS) of 221 patients was 14 months. The median OS of the patients with Child-Pugh A class was significantly longer than that with Child-Pugh B and C classes. The OS of the individuals with normal AFP levels was also longer than that with high AFP levels. The OS of the patients with Stage I HCC according to tumor node metastasis (TNM) classification, the female patients and the treated patients group was found to be significantly good. In conclusion, the viral etiology (hepatitis B and C infections) in Turkish population is found to be an important factor in HCC development. The Child-Pugh classification, AFP levels, TNM classification, being female and treatment were determined to be important prognostic factors in HCC patients.

Quantitative Proteomic Signature of Liver Cancer Cells: Tissue Transglutaminase 2 Could Be a Novel Protein Candidate of Human Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common diseases worldwide, with extremely poor prognosis due to failure in diagnosing it early. Alpha-fetoprotein (AFP) is the only available biomarker for HCC diagnosis; however, its use in the early detection of HCC is limited, especially because about one-third of patients afflicted with HCC have normal levels of serum AFP. Thus, identifying additional biomarkers that may be used in combination with AFP to improve early detection of HCC is greatly needed. A quantitative proteomic analysis approach using stable isotope labeling with amino acids in cell culture (SILAC) combined with LTQ-FT-MS/MS identification was used to explore differentially expressed protein profiles between normal (HL-7702) and cancer (HepG2 and SK-HEP-1) cells. A total of 116 proteins were recognized as potential markers that could distinguish between HCC and normal liver cells. Certain proteins, such as AFP, intercellular adhesion molecule-1 (ICAM-1), IQ motif containing GTPase activating protein 2 (IQGAP2), claudin-1 (CLDN1) and tissue transglutaminase 2 (TGM2), were validated both in multiple cell lines and in 61 specimens of clinical HCC cases. TGM2 was overexpressed in some of the AFP-deficient HCC cells (SK-HEP-1 and Bel-7402) and in about half of the tumor tissues with low levels of serum AFP (17/32, AFP-negative HCC). Trace amounts of TGM2 were found to be expressed in the samples with high serum AFP (26/29, AFP-positive HCC). Moreover, TGM2 expression in liver tissues showed an inverse correlation with the level of serum AFP in HCC patients. Notably, TGM2 existed in the supernatant of the AFP-deficient SK-HEP-1, SMMC-7721 and HLE cells, and it was found to be induced in AFP-producing cells (HepG2) by specific siRNA silence assay. Serum TGM2 levels of 109 HCC patients and 42 healthy controls were further measured by an established ELISA assay; the levels were significantly higher in HCC patients, and they correlated with the histological grade and tumor size. These data suggest that TGM2 may serve as a novel histological/serologic candidate involved in HCC, especially for the individuals with normal serum AFP. These novel findings may provide important clues to identify new biomarkers of HCC and indirectly improve early detection of the disease.

Unterschiedliche klinische Symptomatik des hepatozellulären Karzinoms

A hepatocellular carcinoma was found in the cirrhotic liver of a 45-year-old man in the absence of previous hepatitis B and with a normal alpha-fetoprotein level in serum. This is contrasted with the case of a 57-year-old man with "typical" findings of a hepatocellular carcinoma in a small-nodular cirrhotic liver after viral hepatitis B and markedly elevated alpha-fetoprotein.

Serum alpha-fetoprotein (AFP) levels in breastfed infants with prolonged indirect hyperbilirubinemia

The aim of this prospective study was to verify normal serum AFP (alpha-fetoprotein) levels in jaundiced breastfed infants with indirect hyperbilirubinemia. Methods The study was conducted in clinically jaundiced breastfed infants, 20, or more, days old, referred to our outpatient ambulatory. Inclusion criteria were: birth at term after a physiologic pregnancy, with an Apgar score > 7 at 1 and 5 min, no evidence of congenital anomalies or diseases, direct bilirubin < 1 mg/dl, normal values of α-1-antitrypsin, glucose-6-phosphate dehydrogenase, thyroid stimulating hormone, triiodothyronine, tyroxine, and normal growth. 30 non-jaundiced breastfed infants age–weight-matched, were used as control group. Results 98 jaundiced breastfed infants satisfied inclusion criteria. Their mean serum concentration of AFP was significantly higher than control infants (3548 vs 1095 ng/ml, p < 0.001). Serum AFP levels of jaundiced infants were directly associated with serum indirect bilirubin and γ-glutamyltranspeptidase concentrations. Conclusions The most probable explanation of elevated AFP in jaundiced breastfed infants may be the presence in human milk of one or more factors which affect hepatocyte growth and/or function. Based on our finding we demonstrated that in jaundiced breastfed infants normal range of serum AFP levels are higher than previously published data for healthy infants. Our data can be useful for a right interpretation of AFP levels in breastfed infants with prolonged jaundiced and may be used to avoid unnecessary investigations.

Hepatobiliary and pancreatic: Hepatocellular carcinoma without cirrhosis

A 56-year-old woman presented to our Emergency Service with a 1-week history of upper abdominal pain, nausea and vomiting. On examination of her abdomen, she had a large tender mass in the right upper quadrant. Abnormalities on blood tests included an elevated white cell count (13.2 × 109/L) and a mild elevation of plasma alkaline phosphatase and gamma glutamyltransferase. The serum level of alpha fetoprotein was markedly elevated at 32 311 u/mL (R < 10 U/mL). Serological tests for hepatitis B and hepatitis C were negative. A magnetic resonance imaging scan (T2-weighted) showed a hypervascular mass, 21 cm × 15 cm in size, in the right lobe of the liver (Fig. 1). In some slices, there were extensive areas of necrosis. Upper gastrointestinal endoscopy and colonoscopy were normal. At laparotomy, an extended right hepatectomy was performed. A macroscopic examination of the specimen showed an ill-defined tumor with areas of necrosis (asterisk) including one area of necrosis that perforated through the hepatic capsule (Fig. 2). Microscopic evaluation revealed a moderately differentiated hepatocellular cancer with a predominant microtrabecular pattern but with areas of acinar and tubular formation. The mitotic count was high showing 11 mitoses/10 high power fields (400x). There was no evidence of fibrosis in liver tissue adjacent to the tumor. She was subsequently treated with thalidomide, 300 mg per day, and eight months after surgery, is asymptomatic with normal levels of alpha fetoprotein. Hepatocellular cancer is the fifth most common cancer world-wide. Approximately 50% of cases have been attributed to hepatitis B and 25% to hepatitis C. Most of these patients have coexisting cirrhosis. The remaining 25% of cases have been associated with other causes of cirrhosis such as alcohol abuse and hemochromatosis and to exposure to carcinogens such as aflotoxins. The development of hepatocellular cancer in the absence of cirrhosis appears to be rare in hepatitis C but may be more common in hepatitis B. Another uncommon hepatocellular carcinoma that occurs in the absence of cirrhosis is the fibrolamellar variant. This typically occurs in young adults, does not secrete alpha fetoprotein and is not associated with either hepatitis B or C. The patient described above represents an unusual situation where a typical hepatocellular carcinoma developed in the absence of identifiable risk factors.

Predictors of alpha‐fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy

Elevated serum alpha-fetoprotein (AFP) levels are noted in patients with chronic hepatitis C (CHC) without hepatocellular carcinoma (HCC). The change in AFP levels after treatment with pegylated interferon and ribavirin (Peg-IFN/RBV) combination therapy is still unknown. The aim of this study was to investigate the predictors of elevated serum AFP in patients with CHC, and its change after Peg-IFN/RBV therapy. A total of 123 patients, intended to receive pegylated interferon alfa-2a plus ribavirin therapy, were enrolled. Eighty-three patients had complete treatment and received follow up for and additional 24 weeks. The factors that may affect the elevation of pretreatment AFP and the normalization of post-treatment AFP were determined. The mean AFP level was 18.5 +/- 63.0 ng/mL (range, 1.3-676.0 ng/mL); 41 (33.3%) of the 123 patients had elevated serum AFP (more than 10 ng/mL) at baseline. A multivariate logistic regression analysis disclosed that older age (odds ratio [OR], 1.093; 95% confidence interval [CI], 1.015-1.177; P = 0.018), more advanced METAVIR fibrosis stage (OR, 5.237; 95% CI, 1.244-22.037; P = 0.024), a higher aspartate aminotransferase (AST) level (IU/L) (OR, 1.020; 95% CI, 1.008-1.033; P = 0.001), and lower platelet count (x10(9)/L, OR, 0.985; 95% CI, 0.968-0.994; P = 0.003) were independent determinants of pretreatment AFP elevation. After treatment, 72 of 83 (86.7%) cases were found to have normal post-treatment AFP levels (<10 ng/mL) at the end of follow up (EOF). Post-treatment negativity of the chronic hepatitis C virus (HCV)-RNA (OR, 10.014; 95% CI, 1.000-100.329; P = 0.050) and the post-treatment platelet count (x10(9)/L) (OR, 1.025; 95% CI, 1.001-1.050; P = 0.040) were associated with normal AFP at EOF. AFP progressively decreased with significant differences starting from the 12th week after treatment to the end of treatment, and was lowest at the EOF date for the sustained viral response (SVR) group. On the contrary, the non-SVR group did not have an AFP change during and after treatment. Older age, low platelet count, higher AST levels, and advanced fibrosis predisposed chronic hepatitis C patients without HCC to have elevated serum AFP levels. After Peg-IFN/RBV combination therapy, a higher platelet count and HCV viral eradication were determinants of normal AFP at EOF. Serial AFP levels decreased after treatment, presenting in a time-dependent manner, specifically for the SVR group.

Significance of Primary Tumor Size and Preorchiectomy Serum Tumor Marker Level in Predicting Pathologic Stage at Retroperitoneal Lymph Node Dissection in Clinical Stage A Nonseminomatous Germ Cell Tumors

To determine whether the size of the primary tumor and degree of preorchiectomy serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) elevation predict for retroperitoneal pathologic findings in patients with clinical Stage A nonseminomatous germ cell tumor undergoing primary retroperitoneal lymph node dissection. The testicular cancer database was queried to identify patients with clinical Stage A nonseminomatous germ cell tumor with normalization of serum tumor markers after orchiectomy who had undergone retroperitoneal lymph node dissection. A total of 779 patients were identified. The preorchiectomy serum tumor marker level was recorded and categorized into the following subsets: AFP: less than 20 (normal), 20 to 100, 100 to 1000, and more than 1000 ng/dL; and beta-hCG: less than 5.0 (normal), 5 to 100, 100 to 1000, and more than 1000. The association between AFP, beta-hCG, and primary tumor size and retroperitoneal pathologic findings was determined. The retroperitoneal pathologic examination revealed metastatic disease in 207 patients (26.6%). The preorchiectomy serum beta-hCG level, as a categorical variable, was not predictive of positive retroperitoneal pathologic findings (P = 0.187). The preorchiectomy serum AFP did predict for positive retroperitoneal pathologic findings, with lower serum AFP levels associated with a greater incidence of retroperitoneal metastasis (P <0.001). The primary tumor size was not predictive of positive retroperitoneal pathologic findings (P = 0.113). Neither the primary tumor size nor the preorchiectomy beta-hCG level was predictive of retroperitoneal metastases. However, a normal preorchiectomy AFP level was associated with a greater incidence of retroperitoneal metastases.

Inflammatory Pseudotumor of the Liver Masquerading as Hepatocellular Carcinoma After a Hepatitis B Virus Infection: Report of a Case

We report a rare case of hepatic inflammatory pseudotumor (IPT) after a hepatitis B virus (HBV) infection. Early contrast enhancement on computed tomography (CT) with a washout phenomenon at the delayed phase, and depleted Kupffer cell function on superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) suggested hepatocellular carcinoma (HCC). However, the lack of a tumor capsule, absence of liver cirrhosis, and normal serum levels of alpha-fetoprotein and PIVKA-II (protein induced by vitamin K absence; descarboxyprothrombin) contradicted this diagnosis. We excised the tumor to exclude malignancy, and the histopathological diagnosis was IPT. Recent evidence suggests that this entity has changed from an extremely rare pathology to an established disease. Thus, IPT should be considered in the differential diagnosis of a liver mass with an infectious-inflammatory antecedent. Although surgery is not mandatory, surgical removal is recommended if there is a possibility of malignancy. Further investigations are warranted to elucidate the mechanisms of IPT developing after an HBV infection.

Testicular epidermoid cyst in Klinefelter's syndrome

A 38-year-old Japanese man was referred to our outpatient clinic for treatment of infertility. Semen analysis showed azoospermia. Chromosome analysis revealed a 47XXY karyotype, and non-mosaic Klinefelter's syndrome (KFS) was diagnosed. Upon physical examination, the patient's right testicular volume was 30 mL and the left testicular volume was 3 mL. Laboratory tests showed normal levels of lactate dehydrogenase, alpha-fetoprotein, and human chorionic gonadotropin beta-subunit. The plasma luteinizing hormone and follicle-stimulating hormone levels were increased to 15.7 mIU/mL and 45.9 mIU/mL, respectively. The plasma testosterone was decreased to 0.25 ng/mL. Magnetic resonance imaging showed a right testicular mass of low-signal intensity on the T1-weighted image and of high-signal intensity on the T2-weighted image. Therefore, the final diagnosis was KFS with a right testicular tumor. Thus, a right high orchiectomy was performed. Histological examination revealed an epidermoid cyst of the right testis. Epidermoid cysts in cases of KFS are rare. To our knowledge, only seven cases, including ours, have been reported in the literature.

Successful Embolization of Hepatocelluar Carcinoma With Yttrium-90 Glass Microspheres Prior to Liver Transplantation

We report a case of a patient with end-stage liver disease secondary to hepatitis C, complicated by a large hepatocellular carcinoma. Because of the size of the tumor exceeded the Milan criteria, he was not a candidate for liver transplantation. However, after two treatments with yttrium-90 glass microsphere infusions, the tumor became smaller and the patient's alpha-fetoprotein level dropped to normal range. He was listed for transplantation and subsequently received a deceased donor liver transplant. Two years after his transplantation, he remains tumor free and has normal alpha-fetoprotein levels. This is the first reported case in the literature of using yttrium-90 microspheres as a bridge to liver transplantation in a patient with a large hepatocellular carcinoma. This therapy should be considered in patients with cirrhosis and large hepatocellular carcinomas exceeding current size criterion, who would otherwise be good candidates for transplantation.

Quantitation of alpha-fetoprotein messenger RNA for early detection of recurrent hepatocellular carcinoma: A prospective pilot study

Background: Alpha-fetoprotein (AFP) messenger RNA (mRNA) may be a potential marker of the dissemination of hepatocellular carcinoma (HCC) cells into the circulation. The aim of this prospective pilot study was to assess the prognostic value of quantitative levels of AFP mRNA in patients undergoing ablative treatment for HCC. Methods: Peripheral blood samples were taken from seven patients before and after treatment for measurement of AFP mRNA levels by reverse-transcriptase polymerase chain reaction (RT-PCR). Patients were treated with percutaneous radiofrequency thermal ablation ( n = 3) or transarterial chemoembolization ( n = 4). The level of AFP mRNA in blood was serially determined, and the time course was related to the clinical course and disease outcome. The median duration of follow-up was 14 months (range, 9–16 months). Results: HCC recurred locally in four patients, and lung metastases developed in two of them. Patients were divided into three groups on the basis of the pre- and post-treatment AFP mRNA status. Group 1 included four patients with consistently high serum AFP and AFP mRNA levels (pre- and post-treatment). These patients developed distant and local recurrence. Group 2 included a patient with serum-negative AFP mRNA and normal AFP levels at entry. Although serum AFP remained within normal range, mean AFP mRNA increased from 10 to 95 copies/μg RNA. This patient had no distant metastases, but his tumor markedly increased in size. In Group 3, AFP mRNA and serum AFP remained within normal range before and after treatment. These two patients did not develop either local or distant metastases during the follow-up period. Conclusions: Although this is a small sample size pilot study these findings imply that quantitative measurement of AFP-expressing cells in peripheral blood may serve as a marker of HCC recurrence.

Carboplatin for Stage I Seminoma and the Sword of Damocles

Damocles lived on the island of Sicily approximately 400 BC and served in the court of Dionysius II of Syracuse. As told by Cicero in the Tusculan disputations, Damocles was extremely effusive of the tyrant Dionysius and continuously told him how fortunate he was to have great power and riches. Growing weary of these comments, Dionysius one day asked Damocles if he would like to sample his lifestyle. Damocles happily agreed and was subsequently treated to a bountiful banquet that included the finest foods, wines, flowers, and music. At the end of the meal he glanced up and saw a sharp sword dangling by a single horsehair above his head. Damocles quickly left the banquet, suddenly quite content with his former life. “The Sword of Damocles” has grown to describe the feeling of impending doom. In this issue of the Journal of Clinical Oncology, Aparicio et al have used this metaphor for the stress of the long follow-up experienced by patients during surveillance for clinical stage I seminoma. In their article, the authors report their well-conducted phase II study of a so-called riskadapted strategy in which patients with clinical stage I (a tumor that is apparently confined to the testicle, with normal serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein and normal computed tomography of the chest, abdomen, and pelvis) seminoma were assigned to either surveillance or chemotherapy with carboplatin. Recently, the management of clinical stage I seminoma has become controversial. Is the stress of long follow-up and good compliance eliminated by this approach? In our opinion, the answer is no, as relapses still occur at a rate that may be worse than that observed with standard radiation therapy (RT) and at sites that are different. RT has been the standard primary treatment for clinical stage I seminoma for several decades. After approximately 20 to 25 Gy administered to the retroperitoneal and ipsilateral pelvic lymph nodes (the so-called dog-leg port), the overall recurrence rate is approximately 3% to 5%, and virtually all relapses occur outside the RT portal. The 5-year overall survival rate for patients with stage I seminoma after RT is nearly 100%. Late complications from RT, such as nontesticular second malignancies and cardiovascular disease, have been well described. In the past two decades, surveillance alone has been studied as an alternative approach to the management of patients with clinical stage I seminoma. The relapse rate after orchiectomy alone is approximately 15% to 20%. Investigators at the Princess Margaret Hospital (Toronto, Canada) led the efforts. In a series of 471 patients seen between 1981 and 1994, relapses occurred in 37 patients (16%) on surveillance and in 14 patients (5.7%) treated with RT, with a 5-year actuarial survival rate of 97% and a cause-specific survival rate of 99.8% for those managed with RT (n 245) or surveillance (n 226), respectively. Because most patients on surveillance experienced relapse in the retroperitoneum and received therapeutic RT, only 13 patients (5.7%) on surveillance and 10 patients receiving prophylactic RT required subsequent chemotherapy. Hence all of the patients who experienced relapse were cured with either subsequent RT or chemotherapy. With the success of chemotherapy in patients with disseminated germ cell tumors (GCTs), the role of systemic chemotherapy has been studied in seminomas. Noting that seminoma may be more chemotherapy sensitive than its nonseminomatous counterpart, some investigators have advocated single-agent carboplatin over combination therapy. The report by Aparicio et al from the Spanish Germ Cell Cancer Cooperative Group is one such study. An interesting feature of this article is the investigation of not only the assignment of two cycles of carboplatin as adjuvant therapy for a high-risk and surveillance for a lowrisk group of patients with clinical stage I seminoma, but also the prospective use of a risk algorithm to assign highrisk or low-risk status to this patient population. These risk JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005

MR features of regenerative nodules and dysplastic nodules in the cirrhotic liver

In order to study MR features of the regenerative nodule (RN) and dysplastic nodule (DN) of the cirrhotic liver, 26 cases of cirrhotic liver with RNs and DNs, of which 8 cases accompanied with hepatocellular carcinoma, were subjected to MRI. Eighteen of 26 cases underwent additional enhanced MRI with administration of Gd-DTPA on T1WI and 10 of the 18 cases did additional SPIO (Feridex) enhancement on T2WI. Clinical data showed normal level of alpha-fetoprotein in 18 cases except 8 cases accompanied with HCC. The results showed that 12 cases had RNs with nodules measuring < 1 cm. The MR appearance of those RNs showed isointensity on T1WI and hypointensity on T2WI. The intensity of those RNs was isointense to the surrounding hepatic parenchyma on enhanced MRI with administration of Gd-DTPA or SPIO. Among the 14 cases of DNs, 8 cases had nodules measuring 1-3 cm in size and 6 had macroregenerative nodule measuring > 3 cm. In 8 cases with DNs measuring 1-3 cm in size, 5 cases appeared hyperintense on T1WI and hypointense on T2WI as well as the enhancement as that of nodules with < 1 cm in size; and the remaining 3 cases appeared hypointense on T1WI and hyperintense on T2WI, and were not isointense to the surrounding hepatic parenchyma on enhanced MRI but hyperintense on SPIO enhanced MRI. In 6 cases of macroregenerative nodule measuring > 3 cm in size, 2 cases appeared hyperintense to the surrounding hepatic parenchyma on T1, T2WI and enhanced MRI; 4 cases showed hyperintense on T1WI, and hypointense on T2WI and enhanced MRI. Sometimes, normal vessels were seen to pass through the surface of macroregenerative nodules. It was suggested that RNs of cirrhosis had features on MRI that usually allow distinction from hepatocellular carcinoma but not always from dysplastic nodules (DNs). A helpful distinction between HCC and DNs is that the latter are almost never hyperintense on T2WI. Additionally, low grade DNs appear hypointense on SPIO enhanced MRI.

Stereotactic Radiosurgery Followed by Whole Ventricular Irradiation for Primary Intracranial Germinoma of the Pineal Region

Intracranial germinomas can be cured by radiotherapy and/or chemotherapy. Three patients with pineal germinoma were treated with stereotactic radiosurgery using the gamma knife (10 - 12 Gy) to the tumors followed by whole ventricular irradiation (24 Gy). All patients had solitary pineal tumor measuring less than 3 cm, clinically compatible with germinoma, normal cerebrospinal fluid (CSF) and serum levels of alpha-fetoprotein and beta-human chorionic gonadotropin, no disseminated disease on spinal magnetic resonance (MR) imaging, and no abnormal CSF cytology. All patients showed complete response to the combined radiotherapy, and MR imaging has shown no recurrence of the tumor. Combined radiotherapy using gamma knife radiosurgery is effective for pineal germinoma, and reduced the cost of treatment with less need for hospitalization.

Large cell carcinoma of the lung mimicking a germ cell tumor: The potential value of chromosome analysis

A 43-year-old male with a 20 pack year smoking history presented with a 3-week history of breast enlargement, intermittent headache and blurry vision. Other than gynecomastia, the physical examination, including testicular examination, was normal. Serum beta-human chorionic gonadotropin (β-hCG) level was 2125IU/L, with a normal alpha-fetoprotein level. A scrotal ultrasound showed no abnormalities. CT imaging revealed a 6cm×5cm mass in the posterior mediastinum (Fig. 1A), low density lesions in the liver and spleen, and no retroperitoneal lymphadenopathy.

Hepatocyte proliferation in chronic hepatitis C: correlation with degree of liver disease and serum alpha-fetoprotein.

Hepatocyte proliferation (HP) is an adaptive response to liver injury. The relationships between HP and necroinflammation, fibrosis, and serum alpha-fetoprotein (AFP) levels in chronic hepatitis C virus (HCV) infection, however, are not well understood. Proliferative hepatocytes (Ki-67+) were identified using immunohistochemical staining in formalin-fixed, paraffin-embedded liver tissue from 156 HCV RNA-positive patients with different degrees of liver histopathology. Twenty high-power fields (HPFs) in lobular areas were counted in each specimen. HP increased by 1.22 +/- 0.25 cells/HPF per increase in necroinflammation from grade 0 (median: 0.13; range: [0.1-0.5] cells/HPF) through grade 3 (median: 1.80; range: [0.0-25.2] cells/HPF; P=0.002). HP increased by 0.81 +/- 0.20 cells/HPF per increase in fibrosis from stage 0 (median: 0.33; range: [0.0-1.3] cells/HPF) through stage 3 (median: 1.70; range: [0.0-25.2] cells/HPF) and then decreased in stage 4 (to median: 0.90; range: [0.0-5.3] cells/HPF). HP also increased with advancing age (P=0.03). Among patients with advanced liver disease, HP was no higher in patients with elevated serum AFP levels (median: 1.68; range: [0.1-5.3] cells/HPF) than in those with normal serum AFP levels (median: 1.70; range: [0.0-25.2] cells/HPF; P=0.26). In patients with chronic HCV infection, HP increases with histologic progression of liver disease, but is impaired in cirrhosis. HP was not increased in patients with elevated serum AFP levels.

Experience With Testis Sparing Surgery for Testicular Teratoma

Testicular teratoma is a rare neoplasm affecting the pediatric population and has classically been reported to be the second most common testis tumor in children behind yolk sac tumors. Testicular teratomas are benign and partial orchiectomy may be considered. We describe our single institution experience with testicular teratoma and definitive treatment with testis preserving surgery. We reviewed the pathology records at our institution for all testicular and paratesticular tumors diagnosed between 1976 and November 2002 in males younger than 18 years. We specifically examined the prepubertal incidence of teratoma, including epidermoid cysts, and our experience with testis preserving surgery. Preoperative and postoperative ultrasonography images were used to calculate the atrophy index following surgery. Patients were contacted for long-term followup. Of 77 primary testicular and paratesticular tumors 38 were diagnosed in prepubertal boys (age younger than 13 years) including 11 mature teratomas and 5 epidermoid cysts. Mean patient age at treatment was 34.4 months (range 4 months to 10 years). All boys presented with a painless scrotal mass, cystic foci within an intratesticular mass on ultrasound and a normal alpha-fetoprotein level. Of the 16 boys with benign teratomas 13 (81%) were treated with a testis sparing procedure. At a mean 7-year followup no patient has presented with recurrent tumor in the ipsilateral or contralateral testicle. Postoperative physical examination and scrotal ultrasound were obtained in 9 patients at a median followup of 10.2 months, and there was no evidence of testicular atrophy or persistent discomfort. Unlike previously published series based on tumor registries, benign teratoma was the most common pediatric testicular tumor treated at our institution. Our single institution experience with testis preservation and long-term followup confirms the role and safety of this technique. Testis sparing surgery remains our technique of choice for testicular teratoma.