I-Ping Chiang

Effects of patient factors on noninvasive liver stiffness measurement using acoustic radiation force impulse elastography in patients with chronic hepatitis C

BackgroundPrevious research has shown variation in the effects of patient factors, including hepatic necroinflammatory activity, on liver stiffness measurement (LSM). This prospective study attempts to identify explanatory factors for LSM in patients with chronic hepatitis C (CHC) using acoustic radiation force impulse (ARFI) technology.MethodsA cohort of 127 Taiwanese patients with CHC underwent ARFI LSM and immediate percutaneous liver biopsy. This study compares the concurrent diagnostic performances of LSM and FibroTest using receiver operating characteristic (ROC) curves. Three multiple linear regression models were used to evaluate the significance of concurrent patient factors in explaining LSM.ResultsTo classify METAVIR fibrosis (F) stages, the areas under ROC curves (AUCs) were ARFI LSM, 0.847 (95% confidence interval (CI), 0.779-0.914) and FibroTest, 0.823 (95% CI, 0.748-0.898), for F1 versus F2-4; ARFI LSM, 0.902 (95% CI, 0.835-0.970) and FibroTest, 0.812 (95% CI, 0.735-0.888), for F1-2 versus F3-4; ARFI LSM, 0.831 (95% CI, 0.723-0.939) and FibroTest, 0.757 (95% CI, 0.648-0.865), for F1-3 versus F4. After adjusting for other demographic and biological covariates, biochemical and histological necroinflammatory factors consistently explained LSM. Factors included serum alanine aminotransferase (ALT)/upper limit of normal (ULN) categories (model R2 = 0.661, adjusted R2 = 0.629), ActiTest A scores (R2 = 0.662, adjusted R2 = 0.636), and METAVIR activity (A) grades (R2 = 0.651, adjusted R2 = 0.620). METAVIR F stages, body mass index, and platelet count were also independently associated with LSM. Necroinflammatory degrees, including ALT/ULN, ActiTest A scores, and METAVIR A grades, explained the false positivity of liver fibrosis staging using ARFI LSM.ConclusionsThe degree of hepatic necroinflammatory activity independently and significantly exaggerated liver fibrosis evaluation using ARFI LSM. However, comparisons with concurrent FibroTest indicate that ARFI LSM may be a promising alternative, or adjunctive single indicator, for liver fibrosis evaluation in patients with CHC.

Noninvasive assessment of liver fibrosis via spleen stiffness measurement using acoustic radiation force impulse sonoelastography in patients with chronic hepatitis B or C.

Summary.  Portal hypertension and splenomegaly are common in patients with cirrhosis. However, there is limited previous in vivo research on the correlation between spleen stiffness and stages of liver fibrosis. This study aimed to evaluate the diagnostic value of spleen stiffness measurement (SSM), using acoustic radiation force impulse (ARFI) technology, for liver fibrosis assessment. Eligible patients with chronic hepatitis B or C (n = 163) underwent concurrent liver stiffness measurement (LSM), SSM and percutaneous liver biopsy. Receiver operating characteristic curves estimated the diagnostic performance of SSM, with multiple linear regression models for LSM and SSM determining the significance of explanatory factors. Results indicated significant correlation between LSM and SSM (R2 = 0.574, P < 0.0001). Using SSM to classify METAVIR fibrosis (METAVIR F) scores, the areas under curves were 0.839 (95% CI: 0.780–0.898) for METAVIR F1 vs F2–4, 0.936 (95% CI: 0.898–0.975) for F1–2 vs F3–4 and 0.932 (95% CI: 0.893–0.971) for F1–3 vs F4, all P < 0.001. Multiple linear regression models identified BMI, spleen stiffness, METAVIR F3 and F4, serum alanine aminotransferase, international normalized ratio of prothrombin time, sodium and platelet count as significant independent explanatory factors for liver stiffness (adjusted R2 = 0.724, P < 0.001). Male gender, liver stiffness, METAVIR F2, F3 and F4 also significantly and independently explained spleen stiffness (adjusted R2 = 0.647, P < 0.001). ARFI SSM is potentially useful as a single or adjunct predictor of stages of liver fibrosis.

Effect of Deferiprone on Liver Iron Overload and Fibrosis in Hepatitis C Virus-Infected Thalassemia

To assess the effects of liver iron overload and fibrosis after treatment with a chelating agent in hepatitis C virus (HCV)-infected thalassemia, from April 1999 to July 2004, 45 patients with thalassemia major (age range 9–33 years, mean 19.3) received daily deferiprone (L1) for 23–60 months (75 mg/kg). The patients were divided into two groups on the basis of their hepatitis status (27 with, 18 without). Their serum was analyzed for alanine aminotransferase (GPT), aspartate aminotransferase (GOT), bilirubin (total/direct), r-glutamyl transpeptidase (r-GT), alkaline phosphatase (Alk-P), and ferritin. Liver iron overload and fibrosis were defined by a senior pathologist. No significant differences were demonstrated in serum levels of GPT, GOT, bilirubin, r-GT, Alk-P or ferritin; comparison was made for each group before and after L1 treatment. Iron scores were 2.3 ± 0.9 and 2.8 ± 0.9 for the hepatitis C negative and positive groups, respectively (p = 0.07), with liver fibrosis scores of 1.0 ± 0.5 and 0.4 ± 0.52 (p = 0.56). The two scores were not higher for the positive group. There was no evidence of: 1) greater iron overload and fibrosis in the HCV-infected thalassemic patients; 2) L1 inducing progressive hepatic fibrosis or worsening iron overload in HCV-infected thalassemic patients after long-term therapy; 3) further damage to liver cells associated with L1 treatment.

Child With Ataxia Telangiectasia Developing Acute Myeloid Leukemia

An 11-year-old boy, who was diagnosed as having ataxia telangiectasia (AT) at 5 years of age, was referred to our hospital because of a right submandibular progressive enlarged mass for 2 months. He also suffered from being unstable to stand and recently had twisting of the trunk and tremor in all areas of his body. On physical examination, the patient looked pale and had multiple cervical lymphadenopathies and telangiectasia of the bulbar conjunctiva. His gums easily bled, and he had mild gingival hypertrophy. No hepatosplenomegaly or mucocutaneous petechiae were noted. Neurologic examination revealed nystagmus, squint, dysarthric speech, diminished reflexes, dysmetria, and ataxic gait. Laboratory investigations showed leukocytosis, anemia, and thrombocytopenia (WBC count 28,500/ L; platelets 59,000/ L; hemoglobin 5.2 g/L; hematocrit 27.5%). Biochemistry tests revealed ALT of 27 U/L, AST of 29 U/L, blood urea nitrogen of 9 mg/dL, creatinine of 0.5 mg/dL, and lactate dehydrogenase of 352 U/L. The -fetoprotein level was high (242 ng/mL). There were decreased levels of immunoglobulin (Ig) A (6.67 mg/dL) and IgE ( 0.1 mg/dL). Electrophysiologic study showed mild to moderate motorpredominant spinal motor pathology with sensory involvement. Brain magnetic resonance images revealed isolated cerebellar atrophy with small size of vermis (Fig 1). The ventricles were all normal. Analysis of the ATM gene revealed compound heterozygous mutation (2413 C to T, arg805ter; 1402-3 del AA, lys468fs). Bone marrow examination showed hypercellularity with an excess of blastic cells (80% to 85%) with primitive nuclear morphology, little cytoplasm, easily discernible nucleoli, and distinct nuclear membrane and markedly depleted hematopoietic cells (Fig 2). These blasts were positive in peroxidase stain (Fig 3) but negative in periodic acid-Schiff stain. Flow cytometric analysis of the bone marrow aspirate revealed the following: CD13, 42.51%; CD33, 77.33%; CD34, 43.64%; HLA-DR, 34.71%; and negative for Band T-cell markers. The karyotype of the bone marrow cells was 45,XY, 7, 10,t(12;14)(p11.2;q32), 14, 22. Acute myeloid leukemia (AML) was diagnosed. After AML was diagnosed, the patient received chemotherapy according to the Taiwan Pediatric Oncology Group AML-97A protocol. Induction treatment consisted of cytarabine (100 mg/m, continuous infusion, days 1 to 7) and idarubicin (9 mg/m, intravenous push, days 1 to 3). Intrathecal methotrexate (15 mg) was administered on day 1. However, the patient did not achieve remission after two courses of induction therapy and consequently died as a result of severe pneumonia. Fig 2.

Successful Treatment of Fosinopril-Induced Severe Cholestatic Jaundice with Plasma Exchange

Objective: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. Case Summary: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patients jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. Discussion: Angiotensin-converting enzyme (ACE) inhibitor–induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor–induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. Conclusions: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.

Hepatic macronodular tuberculoma mimics liver metastasis in a patient with locoregional advanced tongue cancer

Case Report A 55-year-old man had disseminated tuberculosis involving the lungs and right foot, with initial presentation of complicated right foot cellulitis. He had undergone antituberculosis treatment with combined use of pyrazinamide, rifampin, ethambutol, and isoniazid in April 2005. Other than the persistent abnormal appearance of plain chest radiographs, there were no clinical events thereafter. However, in September 2010, the patient presented with gradual dysphagia and odynophagia. On physical examination, an enlarged and indurated mass was noted on the left hemitongue. Several enlarged, painless, and fixed lymph nodes were palpable on the left upper neck region. Laboratory studies revealed normal blood counts, liver function tests, renal function, and inflammatory biomarkers. Incisional biopsy of the tongue mass confirmed the diagnosis of squamous cell carcinoma (SCC). Contrast-enhanced computed tomography (CT) of the head/ neck, chest, and upper abdomen for pretreatment evaluation revealed locally advanced tongue cancer (Fig 1A; arrow) and lymph node metastases in the left upper neck (Fig 1B; arrowhead). In addition, patchy consolidation with cystic, calcified, and fibronodular change was noted in the left lung (Fig 1C), compatible with pulmonary tuberculosis also confirmed by the subsequent polymerase chain reaction assay for Mycobacterium tuberculosis complex from the patient’s sputum. Nevertheless, a hypodense nodule with minimal enhancement, measuring 16 12 mm, was found in segment four of the liver (Figs 2A, 2B; arrows). For further differentiation of the hepatic lesion and whole-body survey of the tongue cancer, fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was performed, revealing hypermetabolic lesions suggestive of malignancy in the left tongue (Fig 2C; maximum standardized uptake value [SUVmax], 13.2) and bilateral upper neck regions (Fig 2C; SUVmax, 3.2). Moreover, it also showed heterogeneous intense radioactivity (SUVmax, 2.8) in the left upper lung region (Fig 2C), compatible with an active inflammatory process such as pulmonary tuberculosis. Nevertheless, abnormal FDG uptake (SUVmax, 3.0) was also found in segment four of the liver (Figs 2C to 2E; arrowheads). Although the character of FDG uptake in the hepatic lesion might have been attributable to malignancy, an inflammatory process such as tuberculosis was also possible, because the lungs revealed probable active inflammation as with pulmonary tuberculosis. However, whether hepatic tuberculoma or hepatic metastasis from locoregional advanced tongue cancer, it was an unusual clinical manifestation. To determine a treatment strategy, it was necessary to obtain pathologic confirmation of the hepatic lesion. Histologic examination of the hepatic nodule via CT-guided biopsy revealed caseating granulomatous inflammation characteristic of hepatic tuberculoma (Fig 3; hematoxylin and eosin stain, 200). As a result, this patient then underwent surgery for the tongue cancer and neck lymph node metastases, with the resulting pathologic stage of T4aN2cM0, stage IVA. Adjuvant chemoradiotherapy was initiated postoperatively.

Langerhans cell histiocytosis with thyroid and lung involvement in a child: a case report.

SUMMARY Langerhans cell histiocytosis (LCH), a monoclonal disease of histiocytes, may involve several organ systems but rarely primarily involves the thyroid gland. This report presents an extremely rare case of LCH of the thyroid and lungs in a 3-year-old boy who presented with a neck mass for several weeks. The patient subsequently underwent chemotherapy with resolution of the goiter and lung findings, and the patient remained in complete remission 1 year after chemotherapy. LCH of the thyroid should be considered in the differential diagnosis of a child with a thyroid mass. Pulmonary examination should be done in these patients.

Synchronous squamous cell carcinomas of the esophagus and renal pelvis.

A 55-year-old man was incidentally diagnosed with a superficial squamous cell carcinoma of esophagus. However, the systemic survey with FDG PET/CT revealed a picture of more advanced disease because of the regional lymph node metastases and a suspected distal metastasis in the left renal pelvis, which was somewhat strange for a small superficial esophageal cancer. Subsequently, the renal pelvic lesion was confirmed as squamous cell carcinoma. However, a primary tumor rather than metastasis in the renal pelvis was considered according to the histologic characteristics and radiologic findings.

Primary Renal Rhabdomyosarcoma in an Adolescent With Tumor Thrombosis in the Inferior Vena Cava and Right Atrium: A Case Report and Review of the Literature.

AbstractAlthough the second peak of the age distribution of rhabdomyosarcoma (RMS) is at adolescence, renal RMS is extremely rare at this age group. This tumor is indistinguishable from other renal tumors based on clinical and imaging findings, and the diagnosis relies on histology and immunohistochemical staining. We report a unique case of adolescent renal RMS associated with tumor thrombus extending into the inferior vena cava (IVC) and right atrium.An 18-year-old female adolescent presented with shortness of breath and palpitations, associated with right flank discomfort, and hematuria. A pleomorphic-type renal RMS with Budd–Chiari syndrome and arrhythmia induced by IVC and RA thrombosis was diagnosed. Despite complete tumor resection, the patient developed multiple lung metastases a month after surgery. Chemotherapy was recommended, but the patient declined. She died within a year of the initial operation.Adolescent renal RMS is rare and associated with poor outcome. Early aggressive multimodal therapy seems to be appropriate, in particular, in the presence of tumor thrombosis.

Carcinoid Tumor of the Jejunum with Perforation

Perforation is a rare complication of intestinal carcinoid tumor. Only 11 cases have been reported in the literature and most of them were located at the ileum, appendix, and Meckels diverticulum. A 71-year-old woman presented with postprandial abdominal fullness and complained of significant body weight loss within the previous two months. During admission, she was suffering from acute abdomen. Computed tomography showed free air in the abdomen. Urgent exploratory laparotomy disclosed a predominantly submucosal tumor extending through the thickness of the muscle layer and mucosa with transmural perforation at the jejunum. Histopathological and immunohistochemical studies were typical of carcinoid tumor. We herein report perforation of a small bowel carcinoid tumor at an unusual site.