Nasal angiosarcoma metastatic to the larynx: Case report and systematic review of the literature.

BACKGROUND: Laryngeal angiosarcoma is rare and the prognosis is poor. The purpose of this study was to describe the first case of cutaneous angiosarcoma metastatic to the larynx and systematically review all cases of laryngeal angiosarcoma. METHODS: A 61-year-old man presented with an alar lesion diagnosed as angiosarcoma and was treated with wide local resection and radiation. Six years later, he presented with a laryngeal mass histologically similar to the initial tumor. A systematic review of reported cases of angiosarcoma of the larynx was performed. RESULTS: Eighteen cases were identified. Mean age of presentation was 64.3 years. Men represented 66.7%. Mean follow-up was 34.1 months. Forty-seven percent died with disseminated disease at a mean of 18.4 months. Our patient did well with serial resection. CONCLUSION: To the best of our knowledge, this case represents the first documented case of cutaneous angiosarcoma metastatic to the larynx and suggests that serial resection with long-term surveillance may be of benefit in some cases.

Treatment eligibility in Alaska Native and American Indian persons with hepatitis C virus infection.

OBJECTIVES: Treatment with pegylated interferon and ribavirin may prevent progression of liver disease among patients with chronic hepatitis C virus infection (HCV). Treatment initiation is based on published clinical eligibility criteria, patients' willingness to undergo treatment and likelihood of success. We examined treatment eligibility in a cohort of Alaska Native and American Indian persons with chronic HCV infection. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all treatment naïve HCV RNA positive patients given an appointment by hepatology specialty clinic staff in 2003 and 2007 were evaluated by a hepatology provider to investigate documented reasons for treatment deferral. RESULTS: Treatment was initiated in 4 of 94 patients (4%) in 2003 and 14 of 146 patients (10%) in 2007. Major reasons for treatment deferral in 2003 versus 2007 included inconsistent appointment attendance (36% of deferrals vs. 18%), active substance abuse (17% vs. 22%), patient decision (17% vs. 27%), liver biopsy without fibrosis or normal ALT (8% vs. 3%), uncontrolled psychiatric condition (7% vs. 7%) and concurrent medical condition (6% vs. 9%). There was significant improvement in proportion of appointments attended in 2007 versus 2003 (76% vs. 67%, p = 0.04) and the percentage of patients attending at least 1 appointment (84% vs. 66%, p = 0.002). CONCLUSIONS: Multiple reasons for treatment deferral were documented. Despite a significant improvement in hepatology clinic attendance and an increase in the number of patients started on treatment in 2007 compared to 2003, the overall percentage of those treated remained low.

Cystic adventitial disease of the common femoral vein.

Cystic adventitial disease of blood vessels is a rare condition, more so when veins are involved. We report the case of a 36-year-old man who was referred to us after an intraoperative diagnosis of a left common femoral vein mass. This patient, who had a history of deep vein thrombosis and pulmonary embolism, had presented to an outside facility with recurrent left lower extremity pain and swelling. At our hospital, he underwent excision of the vein mass with interposition vein grafting using the left internal jugular vein. In this report, we discuss the presentation, diagnosis, treatment, and pathology of this rare condition.

Genetic diversity of near genome-wide hepatitis C virus sequences during chronic infection: evidence for protein structural conservation over time.

Infection with hepatitis C virus (HCV) is one of the leading causes of chronic hepatitis, liver cirrhosis and end-stage liver disease worldwide. The genetics of HCV infection in humans and the disease course of chronic hepatitis C are both remarkably variable. Although the response to interferon treatment is largely dependent on HCV genotypes, whether or not a relationship exists between HCV genome variability and clinical course of hepatitis C disease still remains unknown. To more thoroughly understand HCV genome evolution over time in association with disease course, near genome-wide HCV genomes present in 9 chronically infected participants over 83 total study years were sequenced. Overall, within HCV genomes, the number of synonymous substitutions per synonymous site (d(S)) significantly exceeded the number of non-synonymous substitutions per site (d(N)). Although both d(S) and d(N) significantly increased with duration of chronic infection, there was a highly significant decrease in d(N)/d(S) ratio in HCV genomes over time. These results indicate that purifying selection acted to conserve viral protein structure despite persistence of high level of nucleotide mutagenesis inherent to HCV replication. Based on liver biopsy fibrosis scores, HCV genomes from participants with advanced fibrosis had significantly greater d(S) values and lower d(N)/d(S) ratios compared to participants with mild liver disease. Over time, viral genomes from participants with mild disease had significantly greater annual changes in d(N), along with higher d(N)/d(S) ratios, compared to participants with advanced fibrosis. Yearly amino acid variations in the HCV p7, NS2, NS3 and NS5B genes were all significantly lower in participants with severe versus mild disease, suggesting possible pathogenic importance of protein structural conservation for these viral gene products.

Factors associated with the progression of fibrosis on liver biopsy in Alaska Native and American Indian persons with chronic hepatitis C.

BACKGROUND: Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection. OBJECTIVES: To examine factors associated with fibrosis in a longterm outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies. METHODS: A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression. RESULTS: Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors. CONCLUSIONS: The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.

S100, HMB-45, and Melan-A negative primary melanoma.

The diagnosis of malignant melanoma can be challenging given the wide variation in morphologic features and immunohistochemical stains are often used to confirm the diagnosis. We report a case of melanoma with loss of staining for S100 protein, HMB-45, and Melan-A, with retained expression of tyrosinase. Regional lymph node metastases showed positive S100 protein staining. Although the loss of phenotypic markers including S100 protein has been reported in metastatic melanoma, loss of S100 in primary melanoma is rare. Discordant staining between primary and metastatic lesions further emphasizes the protean nature of melanoma.

Factors predictive of significant hepatic fibrosis in adults with chronic hepatitis B and normal serum ALT.

GOAL: This study examines the prevalence and correlates of significant liver fibrosis among patients with immunotolerant hepatitis B. BACKGROUND: Adults with chronic hepatitis B infection acquired early in life often have normal serum alanine aminotransferase (ALT) activity and high serum hepatitis B virus deoxyribonucleic acid loads (HBV DNA), known as "immunotolerant" hepatitis B. STUDY: We conducted a cross-sectional study of 28 hepatitis B patients with serum HBV DNA titer >10 copies/mL, positive hepatitis B envelope antigen, and persistently normal serum ALT in a tertiary care setting. Liver biopsies were reviewed by a single pathologist who was blinded to other data. The prevalence of significant hepatic fibrosis was determined using the hospital-defined upper limit of normal for ALT and 2 more stringent criteria proposed by recent studies. Statistical analyses were conducted to identify factors associated with hepatic fibrosis. RESULTS: The prevalence of stage 2 fibrosis using the hospital laboratory, more stringent, and most stringent definitions of normal serum ALT, was 32%, 32%, and 13%, respectively, corresponding to negative predictive values of 68%, 68%, and 88%, respectively. Age greater than 30 years (P=0.035), grade 2 liver inflammation (P=0.005), and lower serum HBV DNA level (mean 7.45 vs. 8.42 log10 copies/mL, P<0.001) were independently associated with stage 2 fibrosis on liver biopsy. CONCLUSIONS: These results highlight the need to use stringent definitions of normal serum ALT when making clinical decisions for patients with chronic hepatitis B. Older age and lower serum HBV DNA level predict significant hepatic fibrosis on biopsy. Our findings may guide decisions regarding liver biopsy among patients with immunotolerant hepatitis B.

Hepatitis C virus envelope glycoprotein co-evolutionary dynamics during chronic hepatitis C.

Hepatitis C virus (HCV) envelope glycoprotein co-evolution was studied in 14 genotype 1-infected and treatment-naive subjects, including 7 with mild and 7 with severe liver disease. Cassettes encoding the envelope 1 gene (E1) and hypervariable region (HVR1) of the envelope 2 gene were isolated at 38 different time points over 81 follow-up years. There were no significant differences in age, gender, alcohol use, or viral load between the mild and severe disease groups. Virus from subjects with severe disease had significantly slower evolution in HVR1, and significant divergent evolution of E1 quasispecies, characterized by a preponderance of synonymous mutations, compared to virus from subjects with mild disease. Phylogenetic comparisons indicated higher similarity between amino acid sequences of the E1 and HVR1 regions with mild disease versus severe disease (r=0.44 versus r=0.17, respectively; P=0.01). In summary, HCV envelope quasispecies co-evolution differs during mild versus severe disease.

Correlation of clinical outcome of integra application with microbiologic and pathological biopsies.

BACKGROUND: Integra, a dermal replacement template consisting of bovine collagen, chondroitin-6-sulfate, and a silastic sheet is a postexcisional treatment for deep partial to full thickness burns where autograft is limited. This study correlates Integra histology and quantitative microbiology cultures with clinical outcomes after autografting. METHODS: Charts of 29 burn patients who underwent Integra treatment and neodermis biopsy at the time of ultra thin autografting were reviewed. We analyzed microbial contamination, inflammatory reaction, and autograft take. RESULTS: The mean burn size and age were 43% total body surface area and 39 years old, respectively. In quantitative neodermis cultures, 90% of samples had bacterial growth; nine samples (31%) had > 10(5) colony forming units per gram. The most common organism was Staphylococcus aureus (31%). Patients with quantitative bacterial counts >10(5) CFU/g received targeted systemic antibiotics. Integra take (83%) and autograft take (92%) were acceptable even in patients with high bacterial counts (78% Integra take; 86% autograft take). More than 50% of biopsies had dermal regeneration similar to normal dermis; foreign body reactions were unusual. Histologic evidence of inflammation, especially polymorphonuclear cells, was increased in biopsies with high bacterial counts. CONCLUSION: Integra and autograft take can be acceptable even with high bacterial counts if wounds are treated with appropriate targeted topical and systemic antibiotics in the presence of microbial contamination. Neodermis biopsies showed fibrous in-growth congruent with existing Integra fibers with minimal foreign body reaction. These data support Integra use as a safe and effective treatment modality in patients with major burns.

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis "knows" how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar.

Steatosis and hepatitis C in an Alaska Native/American Indian population.

OBJECTIVES: To determine the prevalence and characteristics of steatosis in Alaska Natives/American Indians (AN/AI) with chronic hepatitis C virus (HCV) infection. STUDY DESIGN: This outcomes study began in 1994, and 988 AN/AI have been enrolled, including 222 study patients with a positive HCV RNA who underwent liver biopsy. METHODS: Study patients were analyzed for sex, age at biopsy, estimated length of infection, body mass index (BMI), genotype, ethanol use, HCV RNA and alanine aminotransferase levels. A pathologist blinded to patient identity and clinical data reviewed all biopsy slides for histologic activity and fibrosis. RESULTS: Moderate to severe steatosis was found significantly more often in genotype 3 than in genotypes 1 and 2 (p = 0.008). On multivariate analysis, BMI > 30 and Ishak fibrosis score > or = 2 were significantly associated with steatosis (p = 0.0013 and 0.0002, respectively), but only genotype 3 was associated with presence of moderate to severe steatosis (p = 0.008). CONCLUSIONS: Our findings in a cohort of AN/AI are consistent with results of previous studies in other groups that steatosis is associated with fibrosis in HCV and infection with genotype 3 is associated with more severe steatosis.

Hepatitis C infection in Alaska Natives with persistently normal, persistently elevated or fluctuating alanine aminotransferase levels.

BACKGROUND/AIMS: An estimated one-third of patients with chronic hepatitis C virus (HCV) infection have persistently normal alanine transaminase (PNALT); however, in many previous studies alanine aminotransferase (ALT) levels were followed for < or = 12 months. METHODS: We analyzed data from a population-based cohort of 935 Alaska Natives with HCV, recruited from 1994 to 2005, to determine the proportion of persons with PNALT, persistently elevated ALT (PEALT), and fluctuating ALT (FLUXALT) to determine factors for each ALT state. We selected persons with two positive HCV RNA results > or = 1 year apart and > or = 6 ALT levels measured over the subsequent 3 years with at least 1 month between ALT measurements (n = 265). We defined a person as having PNALT, PEALT, or FLUXALT when all six ALT levels were normal, elevated, or did not fit either of the above two categories, respectively, during the 3-year follow-up period. RESULTS: Among 208 persistently HCV RNA-positive persons, 13 had PNALT, 121 PEALT, 74 FLUXALT. Among 77 persons who underwent liver biopsy, those with PEALT were more likely to have Ishak fibrosis scores > 2 compared with persons with FLUXALT (44% vs. 10%, OR 7.0, 95% CI: 1.5-33.2). No statistically significant differences were found in ALT classification by age, gender, infection duration, median body mass index, alcohol consumption, residence, risk behavior, RNA level, or genotype. CONCLUSIONS: Only 6% of persons with chronic HCV had PNALT. Persons with PEALT were significantly more likely to have higher fibrosis scores on liver biopsy than those with FLUXALT. Previous studies with short follow-up periods may have overestimated the proportion of persons with normal ALT levels.

Fatal Kaposi's sarcoma-associated immune reconstitution following HAART initiation.

This unique report describes a fatal case of immune reconstitution syndrome associated with Kaposi's sarcoma (KS). This case also illustrates the possibility of cryptic visceral KS with minimal cutaneous disease, as well as the potential for differential responses of cutaneous and visceral KS to treatment.

Prevalence of autoimmune liver disease in Alaska Natives.

OBJECTIVE: There is limited information on the prevalence of autoimmune liver disease in nonwhite populations. We conducted a population-based study on the prevalence of autoimmune liver diseases in Alaska natives. METHODS: Clinical records from 1984 to July, 2000 were reviewed to identify Alaska natives with autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune cholangitis, and overlap syndromes of two of the above. AIH was defined as definite or probable, based on criteria established by the International Autoimmune Hepatitis Group. The diagnosis of PBC was based on a positive antimitochondrial antibody of > or = 1: 40, biochemical evidence of cholestasis, and compatible liver biopsy. Autoimmune cholangitis was defined as PBC but without a positive antimitochondrial antibody. Primary sclerosing cholangitis was diagnosed on the basis of cholangiogram. RESULTS: Seventy-seven patients with possible autoimmune liver disease were identified. Of these, 42 had definite and seven probable AIH. At presentation, 34.7% of patients with AIH presented with acute icteric hepatitis, and 65.3% were asymptomatic. Persons presenting with mild or no symptoms were more likely to have moderate to severe fibrosis on liver biopsy than those presenting with jaundice. Eighteen persons were diagnosed with PBC, five with autoimmune cholangitis, five with overlap syndrome, and none with primary sclerosing cholangitis. The combined point prevalence of AIH Alaska natives was 42.9/100,000 (95% CI = 31-57.7). The prevalence of PBC was 16/100,000 (95% CI = 12.9-25.4). CONCLUSIONS: This population-based study demonstrates that the prevalence rates of AIH and PBC in Alaska natives are comparable with reported rates in other populations.