Evidence for heightened hexokinase II immunoexpression in hepatocyte dysplasia and hepatocellular carcinoma.

BACKGROUND: Normal hepatocytes exhibit low-affinity hexokinase (glucokinase [HKIV]), but during oncogenesis, there is a switch from HKIV to HKII expression. The aims of this study were to compare the immunoexpression of HKII in non-dysplastic cirrhosis (NDC), liver cell change/dysplasia in cirrhosis (LCD), HCC, and normal liver control tissues, and to correlate HKII expression with clinical and histopathological parameters. DESIGN: Immunohistochemistry was performed on a liver cancer progression tissue array consisting of specimens from explants with cirrhosis, including 45 tissue samples with HCC, 108 without HCC, 143 with LCD, and 8 normal liver control tissues. HKII expression was quantified as positive pixel counts/square millimeter (ppc/mm(2)) by image analysis. RESULTS: There was a stepwise increase in HKII level from normal liver tissue to NDC, to LCD, and to HCC (p = 0.001). HKII levels were significantly higher in areas of LCD versus NDC (p ≤ 0.001), and in LCD and HCC versus NDC (p = 0.007). HKII levels were similar in LCD and HCC (p = 0.124). HKII levels were higher in grade 2-4 versus grade 1 HCCs (p = 0.044), and in pleomorphic versus non-pleomorphic HCC variants (p = 0.041). Higher levels of HKII expression in LCD and HCC versus NDC and in higher tumor grade remained significant in multivariate analysis. CONCLUSIONS: Higher levels of HKII immunoexpression in LDC and HCC compared with NDC suggest that upregulation of HKII occurs during the process of hepatocarcinogenesis in humans. In HCC, higher levels of HKII are associated with more aggressive histological features.

Incidence and risk factors for perioperative hyperglycemia in children with traumatic brain injury.

BACKGROUND: Hyperglycemia after traumatic brain injury (TBI) is associated with poor outcome. In this study, we examined the incidence and risk factors for perioperative hyperglycemia in children with TBI. METHODS: A retrospective cohort study of children or=200 mg/dL) and hypoglycemia (glucose <60 mg/dL) was determined. Persistent hyperglycemia was defined as hyperglycemia during any 2/3 (preoperative, intraoperative, and immediate postoperative) study periods, whereas transient hyperglycemia was defined as hyperglycemia during any one study period. Multivariate logistic regression analysis was used to determine the independent predictors of perioperative hyperglycemia. Data are presented as adjusted odds ratio (AOR) (95% CI) and P < 0.05 reflects significance. RESULTS: At least one serum glucose value was recorded during each study period: preoperative (86 [82%]), intraoperative (94 [89%]), and postoperative (101 [97%]). Sixty-four percent of children had less than one glucose recorded per anesthetic hour. Forty-seven (45%) children had hyperglycemia during at least one study period. Transient hyperglycemia occurred in 29 (28%) and persistent hyperglycemia occurred in 18 (17%) children. Independent predictors of perioperative hyperglycemia were age <4 yr (AOR [95% CI]; 3.5 [1.2-10.6]), Glasgow Coma Scale

Primary Atypical Lipomatous Tumor of the Orbit: A Case Report.

PURPOSE: To describe a case of primary atypical orbital lipomatous tumor (ALT). CASE REPORT: A 35-year-old man presented with a two-month history of left eye proptosis and vertical diplopia. His visual acuity was 20/30 OD and 20/60 OS. External examination showed proptosis and downward displacement of the left eye with mild lid erythema. Extraocular movements were reduced in the left eye, with 10% and 70% motility in upgaze and abduction/adduction, respectively. Imaging showed a mass (22 × 16 × 46 mm) in the superior left orbit that infiltrated the orbital fat and the superior rectus muscle. A biopsy of the mass showed mature adipose tissue intermingled with fibrous zones of hyperchromatic stromal cells with nuclear atypia. Fluorescence in situ hybridization analysis demonstrated positive amplification for MDM2/CEP12. The MDM2 to CEP12 ratio was 5:7. A diagnosis of ALT was confirmed. An orbital exenteration was recommended, which the patient declined. CONCLUSION: Although rare, the differential for unilateral proptosis with or without diplopia should include orbital liposarcomas including the ALT subtype. Imaging, biopsy, staining, and/or FISH analysis for proto-oncogenes can assist with diagnosis and staging, while the standard treatment is exenteration.

Detailed Histologic Evaluation of Eosinophilic Esophagitis in Pediatric Patients Presenting with Dysphagia or Abdominal Pain and Comparison of the Histology between the Two Groups.

EoE in children presents with four main symptoms. Most common symptoms exhibited by our clinic population are dysphagia (D) and abdominal pain (AP). Despite similar treatments, we found in an earlier study that the outcomes between these two groups were different. Therefore, we investigated if there exist any histological differences between these groups that could further our knowledge of EoE. Aim. To compare esophageal histology in detail, apart from the eosinophil count, between EoE-D and EoE-AP. Method. Biopsies of patients with EoE-D and EoE-AP were reevaluated for 10 additional histological criteria, in addition to the eosinophil count. Results. Both groups had 67 patients; peak mean eosinophil was 33.9 and 31.55 for EoE-D and EoE-AP (p < 0.05). Eosinophilic microabscesses, superficial layering of eosinophils, and epithelial desquamation were twice as common and significant in EoE-D group than EoE-AP. Eosinophil distribution around rete pegs was also significantly higher in EoE-D group. The remaining criteria were numerically higher in EoE-D, but not significant, with the exception of rete peg elongation. Conclusion. EoE-D patients have significantly higher eosinophils compared to EoE-AP, and the level of inflammation as seen from eosinophil microabscesses, superficial layering, desquamation, and the distribution around rete pegs is significantly higher.

Fine-needle aspiration diagnosis of primary hydatid disease of the thyroid; first reported case in the USA.

Echinococcosis or hydatid disease (HD) is a parasitic disease caused by species of the Echinococcus genus. Since the incidence of HD in the USA is very low and the primary HD of the thyroid is extremely rare even in endemic regions, the occurrence of primary thyroid HD is exceptional in the USA. Thyroid HD is rarely diagnosed by fine-needle aspiration (FNA). Our literature review revealed less than ten cases of primary HD of thyroid diagnosed by FNA worldwide. Hereby, we report the first case of a primary thyroid HD diagnosed by fine-needle aspiration in the USA.

A case report of primary orbital non-Hodgkin's lymphoma causing complete vision loss.

A 29-year-old male with acquired immunodeficiency syndrome presented with a week of left eye blurriness, which then progressed to complete vision loss. On exam, the left pupil was nonreactive to light, and fundoscopy showed significant optic nerve edema. CT and MRI of the left orbit showed a mass lesion compressing the posterior aspect of the sclera with diffuse thickening and contrast enhancement of the retrobulbar portion of the left optic nerve. The lesion demonstrated low T1 and intermediate T2 intensities and heterogeneous contrast enhancement and measured 17.4 mm x 15 mm x 10.6 mm. Anterior orbitotomy with exploration and biopsy were performed. Immunohistochemical studies confirmed diffuse large B-cell lymphoma and a workup showed no systemic involvement. Plans for treatment with chemotherapy and radiation were initiated. Even though rare, primary orbital NHL should be in the differential for relatively acute blindness without other symptoms, especially in patients with AIDS.

Tracheal Diverticulum: A Unique Case with Intraoperative Morphologic Assessment.

There are rare case reports of tracheal diverticula or paratracheal air cysts. These cases, however, were reported mostly as incidental sonographic or radiologic findings without histologic confirmation. Furthermore, the handful of studies that describe this entity histopathologically report only cases in patients with prior respiratory symptoms. Here, we report a rare case of an asymptomatic 60-year-old female with no significant past medical history who presented with primary hyperparathyroidism. She was found to have an incidental right paraesophageal air-filled diverticulum with multiple thin septations on her imaging studies. She was taken to surgery and the histologic examination of the specimen revealed multiloculated cystic cavity lined by respiratory-type columnar epithelium with lymphocytic infiltrate and minor salivary glands within the surrounding stroma, rendering the diagnosis of tracheal diverticula.

Fulminant hepatic failure secondary to primary hepatic angiosarcoma.

Background. Hepatic angiosarcoma is a rare and aggressive tumor that often presents at an advanced stage with nonspecific symptoms. Objective. To report a case of primary hepatic angiosarcoma in an otherwise healthy man with normal liver function tests two months prior to presenting with a short period of jaundice that progressed to fulminant hepatic failure. Methods. Case report and review of literature. Conclusion. This case illustrates the rapidity of progression to death after the onset of symptoms in a patient with hepatic angiosarcoma. Research on early diagnostic strategies and newer therapies are needed to improve prognosis in this rare and poorly understood malignancy with limited treatment options.

Role of IL-6 in the resolution of pancreatitis in obese mice.

Obesity increases severity of acute pancreatitis and risk of pancreatic cancer. Pancreatitis and obesity are associated with elevated IL-6, a cytokine involved in inflammation and tumorigenesis. We studied the role of IL-6 in the response of lean and obese mice to pancreatitis induced by IL-12 + IL-18. Lean and diet-induced obese (DIO) WT and IL-6 KO mice and ob/ob mice pretreated with anti-IL-6 antibodies were evaluated at Days 1, 7, and 15 after induction of pancreatitis. Prolonged elevation of IL-6 in serum and visceral adipose tissue was observed in DIO versus lean WT mice, whereas circulating sIL-6R declined in DIO but not lean mice with pancreatitis. The severe inflammation and lethality of DIO mice were also observed in IL-6 KO mice. However, the delayed resolution of neutrophil infiltration; sustained production of CXCL1, CXCL2, and CCL2; prolonged activation of STAT-3; and induction of MMP-7 in the pancreas, as well as heightened induction of serum amylase A of DIO mice, were blunted significantly in DIO IL-6 KO mice. In DIO mice, production of OPN and TIMP-1 was increased for a prolonged period, and this was mediated by IL-6 in the liver but not the pancreas. Results obtained in IL-6 KO mice were confirmed in ob/ob mice pretreated with anti-IL-6 antibodies. In conclusion, IL-6 does not contribute to the increased severity of pancreatitis of obese mice but participates in delayed recovery from acute inflammation and may favor development of a protumorigenic environment through prolonged activation of STAT-3, induction of MMP-7, and sustained production of chemokines.

Nucleometric study of anisonucleosis, diabetes and oxidative damage in liver biopsies of orthotopic liver transplant recipients with chronic hepatitis C virus infection.

Anisonucleosis is defined as a morphological manifestation of nuclear injury characterized by variation in the size of the cell nuclei. It has been described in variety of benign conditions and is most pronounced in dysplasia and malignancy. To better understand the pathogenesis of anisonucleosis in liver diseases, this study focused on hepatocyte anisonucleosis in biopsies of liver transplant recipients who developed recurrent chronic hepatitis C virus (HCV) infection. Post transplant surveillance liver biopsy specimens were evaluated employing light microscopy, immunohistochemistry, digital image analysis, and nucleometry for histopathological analyses, measurement of nuclear size, and quantification of tissue expression of oxidative marker 8-hydroxy-2'deoxyguanosine (8-OHdG). Our aim in this study was to determine whether there were any independent associations between hepatocyte anisonucleosis and various clinicopathological parameters. These features included patient age, body mass index, gender, race, donor age, live versus cadaveric donor status, history of diabetes mellitus, history of tacrolimus and cyclosporine therapy, duration post transplant and parameters of hepatitis activity index, fibrosis index, steatosis, and oxidative tissue damage in formalin fixed paraffin embedded (FFPE) liver biopsies as determined by immunohistochemistry using 8-OHdG, an indicator of hydroxyl radical mediated tissue damage. Our findings suggested that in liver transplant recipients with recurrent chronic HCV infection, hepatocyte anisonucleosis is more pronounced in individuals with diabetes mellitus (p = 0.0016), and among those who have heightened hepatic expression of the oxidative damage marker 8-OHdG (p = 0.0053). Further studies are necessary to determine whether anisonucleosis is an independent marker for diabetes or oxidative damage.

Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh.

There are a growing number of cases detailing acute hepatic necrosis in patients taking black cohosh (Cimicifuga racemosa), an over-the-counter herbal supplement for management of menopausal symptoms. Our aim is to illustrate two cases of liver injury following the use of black cohosh characterized by histopathological features mimicking autoimmune hepatitis. Both patients reported black cohosh use for at least six months and had no evidence of another cause of liver disease. Their liver biopsies showed a component of centrilobular necrosis consistent with severe drug-induced liver injury. In addition, the biopsies showed characteristics of autoimmune-like liver injury with an interface hepatitis dominated by plasma cells. Although serum markers for autoimmune hepatitis were not particularly elevated, both patients responded to corticosteroids, supporting an immune-mediated component to the liver injury. Liver injury following the use of black cohosh should be included in the list of differential diagnoses for chronic hepatitis with features mimicking autoimmune hepatitis.