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BackgroundThe Human herpesvirus 8 (HHV-8), causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS, and is the most common HIV-related malignancy worldwide. Lack of a diagnostic assay to detect latent and early stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled the unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based non-invasive biomarker assay for Epidemic KS. MethodsThis was a comparative cross-sectional study involving 27 patients with epidemic KS, and 27 HIV-positive adults with no prior diagnosis, or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants respectively. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA was performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyze the sequencing data. Results Fifteen out of the 27 epidemic KS positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV positive, KS negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs down regulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. ConclusionsThis study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Epidemic Kaposi's sarcoma, which has consistently been the most prevalent malignancy in people with HIV disease, frequently presents with lesions in the oral cavity. Guidelines for treating oropharyngeal lesions with radiotherapy are ubiquitous in the literature. Treatment indications include pain, dysphagia, and obstruction. Radiotherapy dosage and fractionation differ from that prescribed for non HIV-infected people. Current literature reveals better treatment outcomes for people infected with HIV if treatment is managed by practitioners experienced in HIV care. This article presents a review of the literature and a case study of a HIV-infected patient who experienced severe adverse effects of irradiation.

Kaposi’s sarcoma (KS) was first described 100 years ago. This tumor of endothelial origin starts in the skin or mucous membranes. The classical form is rare, affects elderly persons of Mediterannean o

The indications for and outcome of radiotherapy for 226 epidemic Kaposi's sarcomas are reported. The overall likelihood of obtaining complete regression of tumor masses was 68%, although residual purple pigmentation remained in 20%. Local recurrence developed in 9%. The indications for treatment were not equally represented. Palliation of pain or improvement of the patient's appearance were the most common indications for treatment. Kaposi's sarcoma lesions do not all behave in a like manner. Best fit log-linear models of associations among the variables were derived. They demonstrated that the combination of treatment intention, anatomic site, and Karnofsky score predicted the short-term and long-term tumor response. The intention of treatment was closely linked to the anatomic site of treatment and in concert directly influenced outcome. The host's Karnofsky score was an independent predictive factor, but had less impact on outcome than did site or intention. Our data demonstrate that case selection can markedly alter the observed response rate of epidemic Kaposi's sarcoma to radiotherapy. This finding should be considered in future analyses of trials that test the efficacy of treatment for this disease.

PROPÓSITO: Presentamos un caso clínico de sarcoma de Kaposi epidémico de laringe, con revisión y discusión de la literatura. MATERIAL Y MÉTODOS: Paciente varón de 37 años, con antecedentes de SIDA y con clínica de disfonía y diagnosticado de Sarcoma de Kaposi epidémico laríngeo. Se realizó tratamiento con radioterapia. RESULTADOS Y CONCLUSIONES: Tras 3 años del tratamiento, el paciente se encuentra con la lesión laringea controlada. La radioterapia es un tratamiento paliativo de elección en el sarcoma de Kaposi epidémico mucoso. PURPOSE: We present a clinical case of epidemic Kaposi's sarcoma of the larynx, make a review, and discuss the literature MATERIAL AND METHODS: A 37 year old male with AIDS and hoarseness diagnosed of epidemic Kaposi's sarcoma of the larynx. He was treated with radiotherapy. RESULTS AND CONCLUSIONS: Three years after radiotherapy, the patient is free of laryngeal disease. Radiation therapy is the paliative treatment of choice for AIDS-associated epidemic mucous Kaposi's sarcoma.

Between 1963 and 1990, 92 lesions in twenty patients with Kaposi's sarcoma (KS) were treated using radiation therapy (RT). Fifty-nine classic Kaposi's sarcoma (CKS) lesions in 12 patients were treated with 990 cGy in 3 fractions-5,000 cGy in 25 fractions; 39 lesions (66%) showed a complete response (CR), 15 (25%) showed a partial response (PR) with complete symptomatic relief, and 5 lesions (8%) showed no response (NR). Only 6 of 59 lesions (10%) recurred in field with a median recurrence-free duration of 8 months. Thirty-three epidemic Kaposi's sarcoma (EKS) lesions in 8 patients were treated from 1,000 cGy in 5 fractions-3,000 cGy in 10 fractions. Thirty-one EKS lesions (94%) showed CR, and two lesions (6%) showed PR. An extensive review of the literature is also presented in the study here reported.

Between June 1986 and December 1988, we treated 149 patients who had AIDS-related epidemic Kaposi's sarcoma with cutaneous irradiation. According to Mitsayasu's staging, 34 patients (23%) had Stage I disease, 82 (55%) Stage II, 0 Stage III, and 33 (22%) Stage IV. Fifty-eight patients (39%) had previously presented with one or more opportunistic infections. Ninety-four patients (63%) had received previous treatment of their Kaposi's sarcoma: 85 (57%) with interferon and 43 (29%) with vinblastine. Among the 149 patients, we treated 88 (59%) with extended cutaneous irradiation using 4- and/or 8-MeV electron beam energy and 61 patients (41%) with localized irradiation using 45-kVp x-ray energy. The total prescribed dose was 30 Gy: 20 Gy in 2 weeks (2.5 Gy/fraction, 4 times/week), followed by 2 weeks of no irradiation, and then 10 Gy in one week by the same dose schedule. Twenty patients (13%) with edema of the lower limbs were treated using 4-Mv photon therapy with bolus. Of the 131 evaluable patients, 63% achieved a complete remission (CR) and 30% a partial remission (PR) after a mean period of 1.5 months (range: 0.5–3 months). The clinical disease stage, anatomic site, and irradiation technique did not significantly influence the remission rates, although we noticed a higher CR rate when localized irradiation was used (71% vs 55.5% for localized and extended irradiation, respectively; p = 0.08). The overall tolerance was acceptable. Complications were severe epidermitis with skin ulcerations (8% of patients). exudative epidermitis (26%), dry epidermitis (60%), and varying degrees of erythema (6%). Of the 87 patients whose AIDS remained relatively clinically stable during the observation period, recurrences occurred in 56 (64%) after an average of 5.5 months (range: 1.5–12 months). We conclude that radiotherapy is useful and can be recommended as a palliative treatment to relieve pain and physical discomfort or to achieve cosmetic improvements for patients with epidemic Kaposi's sarcoma. We also conclude that radiotherapy is most beneficial in the early stages of disease, when localized treatment is practical.

The Italian Cooperative Group on AIDSTumors (GICAT) is collecting data on the epidemiological and clinical features of Kaposi's sarcoma (KS) in Italy, a country where intravenous drug users (IVDUs) comprise the largest group affected by AIDS. As of December 31st 1989, among 5317 cases of CDC-defined AIDS reported to the National Registry of AIDS, there were 419 (8%) cases of KS. Twenty-five percent of all of the homosexual men with CDC-defined AIDS had KS, while only 3% of the IVDU patients with CDC-defined AIDS had KS. The first case of KS was observed in 1982, 2 cases in 1983, 7 cases in 1984, 17 cases in 1985, 55 cases in 1986, 89 cases in 1987, 120 cases in 1988 and 128 cases in 1989. Of the 226 cases of KS reported to GICAT, 60% were in homosexual men, 21% in IVDUs, and 9% in heterosexuals. An increased number of KS has been observed since 1982, although the number of new cases in the past year seems to have been stable, possibly due to the usual delay in notification. There is, however, an actual decrease of the percentage of KS among AIDS patients, from 18% in 1984 to 6% in 1989. Almost half of the patients had had a diagnosis of AIDS prior to the appearance of KS, but in 25% of the patients KS was the first AIDS manifestation. Almost all patients had skin involvement either alone or in association with other sites, whereas very few patients had only lymph node involvement. Only treatment with alpha-2 interferon was able to obtain complete remission in 9% of evaluable patients.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of epidemic Kaposi's sarcoma involving the conjunctiva is reported. The lesion responded completely to local irradiation without the loss of normal tissue tolerance which has been described at other sides. A review of the literature and guidelines for therapy are presented.

Patients treated for AIDS-associated skin Kaposi's sarcoma from October 1992 to June 1994, by localized irradiation using 100 Kv x-ray energy were reviewed. Given dose was 800 cGy/1 fr for small (less than 1.5 cms) lesions and non-edematous lesions and 3000 cGy/10 fr for the rest. All fields were treated daily. Twenty-two patients received treatment to 251 lesions. Median age was 38 years old (2859). According to Mitsuyasu's staging, 2 pts were stage I, 8 pts were stage II, 1 pts stage HI, and 11 pts stage IV One hundred and ninety lesions were localized in the face, 28 in lower extremities, 24 in superior extremities, and 9 in the thorax. Palliation of pain was the main justification for treatment in all feet lesions, while cosmesis was the rational for the facial lesions. 84% of lesions had some degree of associated edema, and 1% were ulcerated. CR with or without residual pigmentation was achieved in 95.2%, while 4.4% had a PR, and 0.4% NR. Pain was completely relieved in all patients. The overall tolerance was acceptable. Radiotherapy is useful and recommended as a palliative treatment to relieve pain, cosmetic and physical discomfort for those patients with AIDS related Kaposis's sarcoma. Long term control with doses ranging from 800 cGy/1 fr to 3000 cGy/10 fr tailored to the individual patient's needs.

Two hundred twelve patients with acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) were followed prospectively. Univariate and multivariate analyses were performed to determine significant predictors of survival and development of opportunistic infection (OI) from the time of diagnosis of KS. Clinical variables analyzed were age at onset, presence of systemic symptoms, prior or coexistent OI, development of OI greater than 3 months following KS diagnosis, and extent of disease. Laboratory variables analyzed were absolute number of peripheral T-helper lymphocytes (T4), helper/suppressor ratio (T4/T8), serum beta-2-microglobulin, and serum acid labile alfa interferon. Three independent variables were predictive of shorter survival: (1) prior or coexistent OI (P = .02), (2) presence of systemic symptoms (P = .001), and (3) absolute T4 count less than 300 cells/microL (P = .002). Based on survival, patients with AIDS-related KS can be divided into four groups: (1) those with no prior or coexistent OI, no systemic symptoms, T4 greater than or equal to 300 cells/microL (median survival, 31 months): (2) those with no prior or coexistent OI, no systemic symptoms, and T4 less than 300 cells/microL (median survival, 20 months); (3) those with no prior or coexistent OI and presence of systemic symptoms (median survival, 15 months); and (4) those with prior or coexistent OI (median survival, 7 months).

The role of radiotherapy in the treatment of epidemic Kaposi's sarcoma needs to be defined. Over the past 4 years, we have irradiated 47 Kaposi's sarcomas in 38 patients having AIDS. Doses ranging from 800 cGy in 1 fraction to 3000 cGy in 10 fractions over 2 weeks were applied on an individualized basis. Treatment generally was successful in achieving palliation; however, toxicity in certain circumstances argues against indiscriminate use of this modality.

The response to radiotherapy of epidemic Kaposi's sarcoma (EKS) is unusual in that irradiated regions are frequently left with a persistent purple stain, reminiscent of the color of the original tumor, but with no tumor mass. To date there are no published data to indicate whether the persistence of pigmentation can be predicted beforehand or if it has any prognostic import. We reviewed the response to treatment of 118 EKS lesions that were irradiated at New York University (NYU) Medical Center between 1981 and 1986. A total of 86 responded to treatment by complete clearance of the mass. Of these, 29 left residual purple pigmentation within the treatment portal, while 57 did not. Complete response (CR; without residual pigmentation) occurred more often in patients who had higher Karnofsky scores at the time of treatment. However, in terms of ultimate local control or survival, there were no differences between patients whose lesions cleared completely v those in whom pigmentation remained. We conclude that persistent pigmentation represents only a benign remnant of irradiated EKS and has no prognostic import.

Patients with epidemic Kaposi's sarcoma, who are often taking zidovudine, may be treated with cytotoxic chemotherapeutic agents. Both cytotoxic chemotherapy and zidovudine are myelotoxic and we have treated 16 patients with this combination. We report an acceptable rate of anaemia, leucopaenia, thrombocytopaenia and non-haematological side effects. This combination can be safely administered to this group of patients, although much of our experience is with the relatively non-myelotoxic chemotherapeutic agents, bleomycin and vincristine.

To the Editor. —Until recently, Kaposi's sarcoma was an uncommon disease that was usually limited to the skin of the legs of elderly men. Ocular involvement was exceedingly rare, and, to our knowledge, as recently as five years ago there had been fewer than 30 cases reported in the world's literature.1 Recently, ophthalmologists have become aware of a wide variety of ways in which the acquired immunodeficiency syndrome (AIDS) may affect the eye, including involvement by Kaposi's sarcoma. Retinal cottonwool spots and cytomegalovirus retinitis are the most common manifestations of this disease. Retinal periphlebitis, neuro-ophthalmologic motility abnormalities, and conjunctival Kaposi's sarcoma, however, also have been reported. Thus far, most reports of conjunctival epidemic Kaposi's sarcoma describe the clinical and/or pathologic features of this disease but provide little information about treatment. We believe this is the first report to detail the successful treatment by radiation of an aggressive conjunctival lesion

Fourteen untreated patients with epidemic Kaposi's sarcoma stages III and IV were treated with etoposide 150 mg/m2 on 3 consecutive days every 4 weeks. No responses were observed. Myelosuppression was severe with white blood count WHO grade 3-4 in nine patients and with platelets WHO grade 3-4 in one patient. Three patients developed opportunistic infections during therapy. It is concluded that etoposide is inactive in epidemic Kaposi's sarcoma.

Fifteen patients who had Kaposi's sarcoma in conjunction with the acquired immune deficiency syndrome (AIDS) received radiotherapy to a total of 17 selected lesions. All tumors exhibited at least partial regression, and the majority responded completely. The radiosensitivity of these lesions is similar to that observed in the classic form of the disease. We conclude that in appropriately selected cases radiotherapy should be considered the treatment of choice. (JAMA1984;252:934-935)