Acquired Immunodeficiency Syndrome-associated Kaposi Research Articles

Hepatic Involvement in Acquired Immunodeficiency Syndrome-Associated Kaposi's Sarcoma: A Descriptive Analysis on CT, MRI, and Ultrasound.

To retrospectively analyse the different imaging manifestations of acquired immunodeficiency syndrome-associated hepatic Kaposi's sarcoma (AIDS-HKS) on CT, MRI, and Ultrasound. Eight patients were enrolled in the study. Laboratory tests of liver function were performed. The CT, MRI, and Ultrasound manifestations were reviewed by two radiologists and two sonographers, respectively. The distribution and imaging signs of AIDS-HKS were evaluated. AIDS-HKS patients commonly presented multiple lesions, mainly distributed around the portal vein on CT, MRI, and Ultrasound. AIDS-HKS presented as ring enhancement in the arterial phase on contrast-enhanced CT and MRI scanning, and nodules gradually strengthen in the portal venous phase and the delayed phase. AIDS-HKS presented as intrahepatic bile duct dilatation and bile duct wall thickening around the lesion. Five patients (62.5%, 5/8) were followed up. After chemotherapy, the lesions were completely relieved (60.0%), or decreased (40.0%). AIDS-HKS presented as multiple nodular lesions with different imaging features. The combination of different imaging methods was helpful for the imaging diagnosis of AIDS-HKS.

Pulmonary involvement in acquired immunodeficiency syndrome-associated Kaposi’s sarcoma: a descriptive analysis of thin-section manifestations in 29 patients

Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS) was the first malignant neoplasm to be described as being related to AIDS. The lungs are the most common visceral site of AIDS-KS. This study aimed to analyze the computed tomography (CT) manifestations of pulmonary involvement in AIDS-KS. Twenty-nine male patients were enrolled in this retrospective study. Imaging evaluation parameters included lesion distribution, the flame sign, interlobular septal thickening, peribronchovascular interstitium thickening, ground-glass opacity (GGO), dilated blood vessels in lesions, and pleural effusion. A peribronchovascular distribution was observed in all patients, predominantly in the lower lobes. Of the patients, 58.62% (17/29) exhibited the flame sign, 75.86% (22/29) had interlobular septal thickening, 72.41% (21/29) had peribronchovascular interstitium thickening, 82.76% (24/29) had GGO, and 34.48% (10/29) had pleural effusion. Enlarged lymph nodes with a short-axis diameter >1.0 cm were found in 41.38% (12/29) of the patients. Of the 12 patients who underwent contrast-enhanced CT (CECT), 90.91% (11/12) had dilated blood vessels, and nodules, consolidations, and lymph nodes were observed to be strongly enhanced. Intrapulmonary lesions decreased in size or number after appropriate treatment during follow-up. Common CT manifestations of pulmonary AIDS-KS include the flame sign, peribronchovascular distribution, peribronchovascular interstitium thickening, interlobular septa thickening, GGO, dilated blood vessel, and strong enhancement of nodules, consolidations, and lymph nodes. It is helpful to follow up the therapeutic effect of pulmonary AIDS-KS by chest CT.

Evaluation of Plasma Human Herpesvirus 8 DNA as a Marker of Clinical Outcomes during Antiretroviral Therapy for AIDS‐Related Kaposi Sarcoma in Zimbabwe

The usefulness of plasma human herpesvirus 8 (HHV-8) DNA as a marker of response to treatment for acquired immunodeficiency syndrome-associated Kaposi sarcoma (AIDS-KS) in an African setting is unknown. We conducted a prospective pilot study at the Parirenyatwa Hospital Kaposi Sarcoma Clinic (Harare, Zimbabwe) to investigate the hypothesis that the clinical response of AIDS-KS is associated with suppression of HHV-8 DNA. Antiretroviral therapy (ART) was provided as coformulation of abacavir, lamivudine, and zidovudine. Clinical response was defined as survival to week 96 with either complete or partial resolution of KS disease. Ninety ART-naive participants (62 men and 28 women) aged >18 years who had human immunodeficiency virus type 1 (HIV-1) infection and biopsy-confirmed KS were studied; 82% had stage T1 disease. Fifty participants received adjunctive chemotherapy. The median CD4(+) lymphocyte count increased from 124 cells/microL at baseline to 281 cells/microL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log(10) copies/mL, the plasma HHV-8 DNA level decreased from 660 to <25 copies/mL, and HHV-8 DNA level in peripheral blood mononuclear cells decreased from 2790 to 37 copies/10(6) cells (P < .001 for each comparison). There were 14 deaths (16%) and 13 patients (15%) lost to follow-up. The most common cause of death was infection. Clinical response of KS occurred in 17 participants (19%). Pretreatment plasma HHV-8 DNA levels of <660 copies/mL were associated with greater survival (odds ratio, 2.83; 95% confidence interval, 1.07-7.53; P = .04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; P = .006). AIDS-KS tumor responses after ART initiation were limited. Pretreatment plasma HHV-8 DNA level may be a surrogate for KS disease that is in need of intensive clinical management.

Paediatric intussusception caused by acquired immunodeficiency syndrome-associated Kaposi sarcoma

To document the clinicopathological features of paediatric intussusception caused by acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS). Clinicopathological features of six patients with AIDS-KS-associated intussusception were obtained retrospectively from departmental and hospital records. Six debilitated male children, without cutaneous KS, were presented with abdominal pain and vomiting for >1 week. Intussusception was the sentinel of HIV infection in five patients. One patient had been on HAART for 13 months. Three patients each had ileal and ileocolic intussusceptions; two had recurrent intussusception. Bowel resection was performed because of failed reduction, infarction and polypoid lead points in all patients, in addition to perforation and peritonitis in three. Five patients died, the immediate cause being massive hematochezia from anorectal KS and/or septic shock. One patient, who received post-surgical chemotherapy and HAART, is currently in remission. Pathologic examination confirmed intussusception due to KS. AIDS-KS-associated intussusception occurred without cutaneous KS. Resection of the infarcted segment may relieve the presenting obstruction, but recurrent intussusception may occur because every elevated KS is a potential lead point. AIDS-KS-I is rare but fatal in children, unless timely surgical intervention, optimal histopathological diagnosis, and appropriate medical management, including HAART and chemotherapy, are facilitated.

Inflammatory Reactivation and Angiogenicity of Kaposi’s Sarcoma-Associated Herpesvirus/HHV8: A Missing Link in the Pathogenesis of Acquired Immunodeficiency Syndrome-Associated Kaposi’s Sarcoma

K SHV/HHV8 IS A NEWLY described oncogenic virus implicated in several hematological malignancies.[1-4][1]KSHV is consistently found in all the clinical forms of Kaposi’s sarcoma (KS),[1][1] [3][2] [4][3] in primary effusion lymphomas (PEL),[5][4] and in multicentric Castleman’s disease.[3][2] [4

Acquired immunodeficiency syndrome-associated Kaposi's sarcoma and human herpesvirus 8 DNA detection in serial peripheral blood mononuclear cell samples

Human herpesvirus 8 (HHV8) DNA was amplified from peripheral blood mononuclear cells (PBMCs) using PCR in 120 HIV-seropositive in- and outpatients who were enrolled in a cohort study between January 1994 and June 1995. Risk factors for HIV infection were homosexuality/bisexuality alone in 64 cases (30 with Kaposi's sarcoma (KS) and 34 without KS, 4 of whom had KS lesions that appeared during follow-up in the cohort), heterosexual contact alone in 32 cases (among whom 1 woman with KS who was the spouse of a bisexual with KS), and transfusion of blood or blood products alone in 24 cases. Three blood samples at 3-4-month intervals were scheduled for each patient. Twenty-five HIV1-seronegative patients served as controls. A total of 47.1% of homo- or bisexual males with KS and 26.7% of homo- or bisexual males without KS had positive HHV8 DNA detection as compared with 21.9% of patients contaminated by heterosexual contact, 8.3% of blood product recipients and 0% of controls. HHV8 DNA detection was intermittent in all but 3 patients according to sequential sampling. Multivariate analysis showed that AIDS-KS was associated with sexual transmission, mainly homo- or bisexual practices and with HHV8 infection assessed by PCR in PBMCs.

USE OF TROPISM-MODIFIED ADENOVIRUSES FOR TARGETED DNA DELIVERY TO AIDS-KS CELLS VIA THE FIBROBLAST GROWTH FACTOR-RECEPTOR PATHWAY.

Dose-limiting toxicity and chemotherapeutic drug resistance have limited the efficacy of available treatment regimens for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). As a result, despite high initial response rates in AIDS-KS patients, all eventually relapse with their disease. Clearly, it is an ideal time for exploration of new and novel therapeutics for AIDS-KS; gene therapy may prove to be a feasible treatment option for this prevalent and debilitating disease. As an initial step in the exploration of a gene therapy approach for AIDS-KS, we have compared the use of lipid- and adenoviral (Ad)-mediated DNA delivery to AIDS-KS cells While both transfection methods were capable of gene transfer to multiple AIDS- and classical KS cell lines, neither appeared to be ideal for this purpose. Cationic lipids consistently gave transfection efficiencies into KS spindle cells of<5%, as measured by β-galactosidase staining. This expression was extremely short-term, peaking at 24 hr and dropping substantially by 48 hr. Adenovirus was more efficient than lipids at delivering DNA to some KS lines, with transfection efficiencies ranging from 20-100%; in these cases, expression levels of the foreign DNA remained high for at least 6 days. Unfortunately, two immortalized KS cell lines KS Y-1 and KS SLK were poorly transducible with adenovirus(1-5%). Thus, these experiments suggested that the Ad receptor is present at variable levels on different AIDS-KS cells and that for optimal and consistently high levels of gene delivery to this cell type, alternative cell surface molecules for viral binding must be identified and exploited. To this end, we have examined the utility of tropism-modified adenoviruses to deliver foreign DNA to AIDS-KS cells. As basic fibroblast growth factor (bFGF) is expressed at high levels in KS spindle cells and is thought to be an important growth and/or angiogenic factor in development of the disease, we have utilized adenoviruses linked via an antifiber monoclonal antibody to bFGF; these viruses are targeted to the bFGF cell surface receptors FGFR1 and FGFR2. Using both the luciferase and green fluorescent protein (GFP) reporter genes, we have been able to demonstrate dramatically increased infectivity of bFGF-Fab-Ad, as compared to Ad with unmodified fiber, for multiple KS cell lines, including KS Y-1. These findings suggest that tropism-modified adenoviruses may be the method of choice for gene delivery to AIDS-KS cells and serve to validate the development of a gene therapy approach for the disease.

Short report: herpes-like DNA sequences in African-endemic and acquired immunodeficiency syndrome-associated Kaposi's sarcoma.

Recently, the unique nucleic acid closely related to the herpes-like sequences has been found in acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). We have confirmed the presence of herpes-like DNA sequences in six cases of AIDS-associated KS and three of the nine cases of African-endemic KS in adults, but not in eight cases of KS in children from the same area. These sequences were seen in a histologically early stage of KS. Our results suggest that herpes-like DNA sequences may play an important role in the pathogenesis of AIDS-associated KS.

Influence of HIV Epidemic on the Incidence of Kaposi??s Sarcoma in Zambian Children

Acquired immunodeficiency syndrome-associated Kaposi's sarcoma (KS) is well documented in adults. However, very little information is available about KS in the pediatric age group. A retrospectively study was undertaken at the University Teaching Hospital (UTH), Lusaka, Zambia, to define the incidence and clinical profile of KS in Zambian children over the last 13 years and to determine the influence, if any, of the current human immunodeficiency virus (HIV) epidemic on the pattern of pediatric KS. All the histopathological records from 1980 to 1992 were reviewed and all cases of KS along with the total number of malignancies, both in children and adults, were analyzed. Along with this, 17 of 23 case files of pediatric KS patients treated at the UTH since 1984 were retrieved and clinical details recorded. Of a total of 915 cases of KS, 85 (9.25%) were in children < 14 years of age. The age ranged from 7 months to 14 years, with an average of 5.62 years; the male/female ratio was 1.76:1. A significant increase in the incidence of pediatric KS has been recorded since 1987 (p < 0.001). This coincides with the advent of the HIV epidemic in the country. The disease was aggressive and fulminant in pediatric patients. More than 80% HIV seropositivity was detected. Children with blood transfusion-related HIV infection had cutaneous or lymphocutaneous disease, indicating that the mode of acquisition of HIV infection may influence the clinical appearance of KS. Thus, HIV-associated KS in children is becoming a common entity in Zambia. An urgent prospective epidemiologic study is needed to address this problem in HIV-affected regions.

Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice.

Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS.

Histologic predictors of survival in acquired immunodeficiency syndrome-associated Kaposi's sarcoma

The relationship between 22 histologic variables and survival was investigated in 93 patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). All the patients were homosexual men in whom KS was the initial manifestation of AIDS. All patients were followed for at least 12 months or until death. Histologic specimens of the initial KS biopsy were reviewed in a blind manner by two of the authors and were evaluated for the presence of a number of histologic features. In a univariate analysis nodular lesions of KS ( v patch or plaque lesions), the absence of hemosiderin, the absence of irregular vascular spaces, and the presence of spindle cell nodules were all significantly associated with increased length of survival. Two variables previously shown to be related to survival (CD4:CD8 cell ratio, initial lesion on lower extremities) were included in a multivariate analysis (Cox model) in addition to the histologic variables. Complete data were avaiable from 85 patients. In the multivariate analysis a higher helper to suppressor T-cell ratio, initial lesion on lower extremities, presence of spindle cell nodules, and nodular histology ( v patch or plaque histology) were all significantly associated with increased length of survival. These data suggest that in AIDS-associated KS, as in reticuloendothelial neoplasms, histologic features may be useful in idenitifying prognostically different subgroups of patients.

Nonmelanoma Skin Cancer Mortality

To estimate the magnitude of nonmelanoma skin cancer mortality and describe its parameters, we reviewed the medical records of all deaths certified as due to this cause among Rhode Island residents from 1979 through 1987. After excluding acquired immunodeficiency syndrome-associated Kaposi's sarcoma, we confirmed that nonmelanoma skin cancer was the cause of death for 51 individuals, a quarter of the number of melanoma deaths reported. The age-adjusted nonmelanoma skin cancer mortality rate was 0.44/10(5) per year. Fifty-nine percent were due to squamous cell carcinoma, and 20% were due to basal cell carcinoma. Most appeared actinically induced. Among deaths from squamous cell carcinoma, the mean age was 73 years. At least 80% of the squamous cell carcinomas metastasized, and 47% arose on the ear. None appeared due to refusal of treatment. Among deaths from basal cell carcinoma, the mean age was 85 years, and refusal of surgical intervention was documented in 40%. Study of nonmelanoma skin cancer mortality provides for estimation of the magnitude of this problem, complements other studies of prognosis, and helps guide prevention, early detection, and treatment.

The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindle-shaped cells in Kaposi's sarcoma

The human progenitor cell antigen (CD34) is selectively expressed on hematopoietic progenitor cells in the bone marrow. In either cryostat sections of snap-frozen skin, or formalin-fixed paraffin-embedded sections of normal skin, anti-CD34 monoclonal antibody immunostained vascular endothelial cells and perivascular/interstitial dendritic cells, particularly in the reticular dermis. A distinctive population of perifollicular spindle-shaped cells in the midportion of the follicle (ie, bulge area), which is the site of the putative hair follicle stem cells, were CD34 positive, as were spindle-shaped cells in and around the eccrine glands accentuating their basement membrane zone. In patch/plaque--and tumor-stage acquired immunodeficiency syndrome-associated Kaposi's sarcoma lesions, CD34 expression was present on both the proliferating endothelial cells as well as the spindle-shaped stromal cells. CD34 positive endothelial cells and spindle-shaped stromal cells may play important participatory and supportive functions in both normal and diseased skin.

The Human Progenitor Cell Antigen (CD34) Is Localized on Endothelial Cells, Dermal Dendritic Cells, and Perifollicular Cells in Formalin-Fixed Normal Skin, and on Proliferating Endothelial Cells and Stromal Spindle-Shaped Cells in Kaposi's Sarcoma

The human progenitor cell antigen (CD34) is selectively expressed on hematopoietic progenitor cells in the bone marrow. In either cryostat sections of snap-frozen skin, or formalin-fixed paraffin-embedded sections of normal skin, anti-CD34 monoclonal antibody immunostained vascular endothelial cells and perivascular/interstitial dendritic cells, particularly in the reticular dermis. A distinctive population of perifollicular spindle-shaped cells in the midportion of the follicle (ie, bulge area), which is the site of the putative hair follicle stem cells, were CD34 positive, as were spindle-shaped cells in and around the eccrine glands accentuating their basement membrane zone. In patch/plaque--and tumor-stage acquired immunodeficiency syndrome-associated Kaposi's sarcoma lesions, CD34 expression was present on both the proliferating endothelial cells as well as the spindle-shaped stromal cells. CD34 positive endothelial cells and spindle-shaped stromal cells may play important participatory and supportive functions in both normal and diseased skin.

Cutaneous acquired immunodeficiency syndrome-associated Kaposi's sarcoma in pediatric patients

Cutaneous acquired immunodeficiency syndrome-associated Kaposi's sarcoma in pediatric patients

Cutaneous Acquired Immunodeficiency Syndrome-Associated Kaposi's Sarcoma in Pediatric Patients

Kaposi's sarcoma has only rarely been reported in children with acquired immunodeficiency syndrome. In contrast to adult patients, in whom the disease is predominantly cutaneous, among pediatric patients with acquired immunodeficiency syndrome, Kaposi's sarcoma is primarily limited to the lymphadenopathic form. We describe two children with the acquired immunodeficiency syndrome who developed diffuse nodular skin lesions of Kaposi's sarcoma.