Mu-Zon Wu

Tumor invasiveness and prognosis in resected hepatocellular carcinoma. Clinical and pathogenetic implications

In order to elucidate the biologic behavior of hepatocellular carcinoma (HCC), the long‐term prognostic impact of the pathologic features of 143 surgically resected HCC were studied. Seventy‐four were smaller than 5 cm in diameter (small HCC), and 69 were larger (large HCC). This study confirmed that tumor size was an important but not the only determining prognostic factor in HCC. Although cirrhosis could cause hepatic failure, patient mortality was mainly attributable to tumor recurrence, which, in turn, was strongly correlated with the invasive nature of HCC. Tumor invasion to the liver and the intraportal spread were very frequent and particularly extensive in large HCC. In both small and large HCC the noninvasive groups not only had high 4‐year actuarial survival (84.6% and 90%, respectively), but there was also no patient mortality from intrahepatic tumor recurrence. Therefore, it was concluded that invasiveness of an HCC is the most crucial factor in determining the long‐term outcome for the patient, and that the clinical course of resected HCC is predictable in a great majority of the cases. In our small HCC series only 2.4% of HCC were regarded as having true multicentric origin. These findings suggest that the majority of HCC occur unicentrically, and that multiplicity and tumor recurrence result mostly from intrahepatic dissemination. In both small and large HCCs invasive tumors were accompanied by high patient mortality from tumor recurrence even when the tumor was small, indicating that intrahepatic spread may start very early during the growth of HCC.

Somatic mutations of β-catenin play a crucial role in the tumorigenesis of sporadic hepatoblastoma

Hepatoblastoma (HB) is the most common malignant hepatic tumor during early childhood. Its molecular pathogenesis is still poorly understood. Mutations of adenomatous polyposis coli (APC) gene have been identified in sporadic cases and in individuals associated with familial adenomatous polyposis syndrome. beta-catenin is a key element in the cadherin-mediated cell adhesion system and Wnt/wingless pathway, and is controlled by APC. APC affects the degradation of beta-catenin by its NH(2)-terminal phosphorylation on the serine/threonine residues of exon 3. Mutations of these phosphorylation sites are primary targets for activating mutations in several types of human cancer and lead to nuclear accumulation of beta-catenin protein. In this study, we examined nine patients with HB using immunohistochemistry and direct DNA sequencing. All nine cases showed predominant nuclear expression of beta-catenin. Eight cases (89%) showed mutations involving exon 3 of the beta-catenin gene, including five with deletions and three with missense mutations. All five deletions were in-frame deletions without frameshift. The very high frequency of mutations in the beta-catenin gene suggests that beta-catenin mutations are crucial in the tumorigenesis of HB.

Childhood hepatocellular carcinoma develops exclusively in hepatitis B surface antigen carriers in three decades in Taiwan: Report of 51 cases strongly associated with rapid development of liver cirrhosis

To elucidate the etiologic role of chronic hepatitis B virus (HBV) infection and the role of liver cirrhosis in hepatocellular carcinoma (HCC), pathologic and virologic features of the disease were studied in 51 children with HCC; these accounted for 4.3% of 1195 pathologically proven HCC patients examined in the last three decades. Males predominated (M/F = 3.3:1), and the mean age was 11 years (range: 4-15 years). Hepatitis B surface antigen (HBsAg) was detected in the liver and/or serum of 100% of 42 children by immunocytochemical and/or radioimmunoassay, in the serum of 90% of 10 siblings, and more importantly in 94.1% of 17 mothers, suggesting that infection from familial HBsAg carriers, particularly carrier mothers, may contribute to the high incidence. Liver cirrhosis was frequent (74%), especially in the unresectable cases (87%); in the 20 children under 9 years of age, 95% were cirrhotic, a significantly higher level than the 58% of the 26 older children, P less than 0.005. All but one had advanced HCC, with 1-year survival in only 10.5%. The advanced HCC coupled with young age suggests that HCC can develop rapidly. The low positive rates of serum hepatitis B e antigen (HBeAg, 18%) and liver hepatitis B core antigen (11%) coupled with high frequency of liver cirrhosis indicate that an early HBeAg seroconversion to anti-HBe, in association with severe liver injury, may play an important role in the rapid development of HCC in children.

Laparoscopic resection of a primary retroperitoneal mucinous cystadenoma: report of a case.

Primary retroperitoneal mucinous cystic tumors are extremely rare, and although their histogenesis is still uncertain, several theories have been proposed. Traditionally, transabdominal laparotomy and enucleation of the cyst is the treatment of choice and laparoscopic resection has not previously been reported. This paper presents the case of a 48-yearold woman in whom a primary retroperitoneal cystic mass, 15×13×9 cm in size, was successfully resected through the laparoscope. Pathological examination revealed a mucinous cystadenoma with borderline malignancy. The patient had a prompt recovery and there was no evidence of recurrence at her 8-month follow-up. However, the prevention of cystic fluid spillage during laparoscopic manipulation is important, especially when the pathology of the retroperitoneal cyst is unclear.

Diagnosis of Zygosity by Questionnaire and Polymarker Polymerase Chain Reaction in Young Twins

We developed a zygosity questionnaire for use in young twins and assessed its validity using the results of DNA diagnosis. The participants were divided into two groups: 105 pairs of adolescent twins (12–16 years old), 47 pairs of child twins (2–12 years old), and their respective parents. The DNA diagnosis of zygosity was made with polymarker polymerase chain reaction (PCR) amplification of five loci, using the AmpliType PM PCR Amplification and Typing Kit; this method has an accuracy rate of 99.0%. A parsimonious model for each sample was established using stepwise logistic regression analysis of the 20 items of the questionnaire. The total accuracy rate of the model was satisfactory for both parental reports (three items) and self-reports (three items) of adolescent twins (97.4 and 95.6%, respectively), while that for parental reports on child twins (two items) was less satisfactory (92.5%). For adolescent twins, if DNA diagnostic workups were limited to those with discordant reports either from themselves or from their parents, the accuracy rate increased to 100% for parental reports and 98% for self-reports.

Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma.

Citrullinemia is a metabolic disorder characterized by elevated plasma concentrations of citrulline and ammonia. Adult-onset citrullinemia (type II, CTLN2) has been attributed to citrin deficiency caused by mutations in the SLC25A13 gene. CTLN2 is associated with a high incidence of hepatocellular carcinoma (HCC) in Japanese. We report a 48-year-old Taiwanese man with citrullinemia, who was in good health until the age of 34 when he had repeated episodes of consciousness disturbance. Hyperammonia (201 micromol/L) was found during an episode of coma. Liver function and electrolyte levels were normal at that time. Serologic markers of viral hepatitis B and C were negative. Analysis of genomic DNA extracted from peripheral blood leukocytes showed homozygous 851del4 mutation in exon 9 of the SLC25A13 gene on chromosome 7q21.3. Fourteen years after disease onset, at the age of 48, he was admitted due to an episode of coma. Abdominal sonography and computed tomography showed a 2.5 cm tumor in the left lobe of the liver, without evidence of liver cirrhosis. Wedge resection of the tumor was performed and grade 2 HCC was diagnosed. The nontumor part of the resected specimen showed chronic persistent hepatitis with moderate steatosis. The results in this case support that both citrin deficiency and steatohepatitis may contribute to hepatocarcinogenesis.

ANALYSIS OF CASES OF SEXUAL ASSAULT PRESENTING AT A MEDICAL CENTER IN TAIPEI

OBJECTIVE Sexual assault is a form of interpersonal violence with significant consequential health problems. The purpose of this study was to describe the characteristics of the victims, assaults, and associated physical and psychologic trauma of sexual assault cases in Taipei. MATERIALS AND METHODS Data were retrospectively collected from the medical records of sexual assault victims who visited the emergency department of a medical center in Taipei from 1991 to 2003. The characteristics of the victims, assaults, and factors associated with general body and genital trauma were analyzed. RESULTS There were 114 sexual assault victims, including 107 females and seven males, aged from 3 to 49 years (mean, 17.9 years). Overall, 72.3% of victims had evidence of physical trauma. Genital/anal injuries (53.3%) occurred more often than general body trauma (41.0%). The presence of general body injuries was positively associated with physical examination within 72 hours, and negatively associated with a victim age younger than 18 years. Genital/anal lesions were significantly more common in victims without prior sexual intercourse. CONCLUSION The results of physical examination in sexual assault victims were related to early examination, age, and sexual experience.

Intracardiac extension of lung cancer via the pulmonary vein

A 69-year-old male heavy smoker had intermittent haemoptysis for 1 month. He did not have exertional dyspnoea, palpitations or chest pain. Chest radiography showed a mass over the right lower lung (RLL). A CT scan of the chest revealed a dumbbell-shaped tumour with an irregular mass in the RLL field, with a tubular part extending along the right inferior …

Unusual Manifestations of Vertebral Osteomyelitis: Intraosseous Lesions Mimicking Metastases

BACKGROUND AND PURPOSE: Vertebral osteomyelitis can have different imaging manifestations. The purpose of this study was to demonstrate the unusual MR imaging patterns of vertebral osteomyelitis with intraosseous lesions mimicking metastases. MATERIALS AND METHODS: From September 2000 to August 2007, 7 patients were selected from our data base of 214 patients with confirmed vertebral osteomyelitis and MR images. All of those having misinterpreted MR imaging reports and unusual imaging patterns were analyzed. The presence of a peripheral curvilinear area of low signal intensity in an osseous lesion (the rim sign) and a peripheral rim of high signal intensity on T2-weighted images around an osseous lesion (the halo sign) was evaluated. Follow-up MR imaging studies were performed in all patients. RESULTS: The patients were 5 men and 2 women, with an age range of 42–80 years. MR imaging findings of those with vertebral osteomyelitis showed a solitary lesion in 2 and multiple lesions in 5 patients. The intraosseous lesions revealed low signal intensity on T1-weighted images, mixed or high signal intensity on T2-weighted images, high signal intensity on short τ inversion recovery images, and global or marginal enhancement. The rim sign was found in 6 (86%) patients; halo sign, in 7 (100%); preserved intervertebral disks, in 7 (100%); and limited paraspinal or epidural inflammation, in 6 (86%). Images of all patients demonstrated healing or almost healed changes on the follow-up MR imaging studies. CONCLUSION: Vertebral osteomyelitis can have MR imaging patterns mimicking osseous metastases. Recognition of these unusual imaging manifestations, together with clinical and histopathologic analysis, may aid in reaching the correct diagnosis.

Human parvovirus B19 infection in patients with coronary atherosclerosis.

BACKGROUND AND AIMS The identification of possible pathogens for an infectious etiology of atherosclerotic coronary artery disease (CAD) is an expanding field. The present study was undertaken to explore the role of parvovirus B19, a potent infectious agent. METHODS A total of 565 patients were analyzed (90 patients with CAD, and 475 controls). Serologic analysis for human paravovirus B19 (B19) specific IgM and IgG was carried out in all patients. In addition, tissue specimens were obtained from five patients who received heart transplants. Direct in situ polymerase chain reaction (PCR) and immunocytochemistry were performed in the samples to localize B19 DNA. RESULTS Enzyme immunoassay showed that the seropositive rate of anti-B19 IgG in patients with CAD was 1.5- to 2.7-fold more frequent than in healthy controls. Clinical characteristics did not affect the prevalence of seropositivity for B19. However, anti-B19 IgM and B19-specific DNA were not detected in healthy or individuals with CAD. Furthermore, nonradioactive in situ PCR found that the majority of B19-specific DNA was located in the endothelial cells of the thickened intima. CONCLUSIONS Our results first demonstrate a seroepidemiological and histopathological association between chronic B19 infection and CAD, suggesting that B19 infection may have a potential role in the pathogenesis of coronary atherosclerosis.