Kaposi sarcoma (KS) is a rare type of cancer that can affect both the skin and internal organs. The most common symptoms are red or purple patches on the skin. It is caused by the human herpes virus 8 (HHV8). Most people with HHV8 don't develop KS; it mostly develops in people with weakened immune systems. KS is classified into:
AIDS-related Kaposi sarcoma
Endemic African Kaposi sarcoma (widespread common cancer in parts of Africa with high levels of HIV)
Classic Kaposi sarcoma (Non-AIDS-related KS. This is rare, mostly affecting middle-aged and elderly men of Mediterranean or Ashkenazi Jewish descent)
Transplant-related Kaposi sarcoma (an uncommon side effect when the immune system is weakened after a transplant)
PubMed Central search for free-access publications about Kaposi Sarcoma MeSH term: Sarcoma, Kaposi US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
DermIS Includes images of Kaposi's Sarcoma skin lesions. DermIS.net is a dermatology information service (multilingual support; English, German, Spanish, French and other languages). It is a collaboration between two German Universities (Heidelberg and Erlangen).
This list of publications is regularly updated (Source: PubMed).
Tozetto-Mendoza TR, Ibrahim KY, Tateno AF, et al. Genotypic distribution of HHV-8 in AIDS individuals without and with Kaposi sarcoma: Is genotype B associated with better prognosis of AIDS-KS? Medicine (Baltimore). 2016; 95(48):e5291 [PubMed] Free Access to Full ArticleRelated Publications
AIDS-associated Kaposi's sarcoma (AIDS-KS) caused by human herpes virus 8 (HHV-8) is the most severe and resistant form of KS tumor. Our aim was to verify whether there is an association between HHV-8 variability and development of AIDS-KS in Brazil by comparing the HHV-8 variability between individuals without and with KS. Saliva samples and blood, when available, were analyzed by polymerase chain reaction (PCR) techniques for detection of the fragments of ORF K1 of HHV-8, which were then genotyped and analyzed regarding the genetic variability. Our study described 106 positive cases for HHV-8 in the saliva from 751 AIDS patients without previous KS. In addition, we performed a phylogenetic analysis of HHV-8 in 34 of the 106 AIDS patients without KS and in 33 of the 37 patients with active KS. The distribution of HHV-8 genotypes A, B, C, and F in AIDS individuals was indistinguishable by comparing non-KS and KS groups, as well as regarding ethnicity. Considering the KS group, genotype B was associated with better prognosis of KS tumor. Interestingly, we found a particular profile of diversity within clade C and 2 recombinant patterns of HHV-8 in the saliva of AIDS individuals without KS. We emphasize the need to achieve standard genotyping protocol for ORF K1 amplification, thus allowing for substantial detection of HHV-8 variants. Our findings can shed light on the role of HHV-8 variability in the pathogenesis of AIDS-KS.
Yang H, Lu QL, Wu XJ, et al. Association of genetic variations in miR-146a rs2910164 and miR-149 rs11614913 with the development of classic Kaposi sarcoma. Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Classic Kaposi sarcoma is a type of vascular proliferative inflammatory disease. Previous studies have reported significant associations between microRNAs expression and the development of classic Kaposi sarcoma. Here, we conducted a case-control study to investigate the association between miR-146a and miR-149 genetic polymorphisms and risk of classic Kaposi sarcoma in a Chinese population. Both classic Kaposi sarcoma patients and healthy controls were recruited between December 2013 and October 2015. Genotyping of miR-146a and miR-149 was performed by polymerase chain reaction-coupled with restriction fragment length polymorphism. Results showed that the GG genotype of miR-146a was associated with increased risk to classic Kaposi sarcoma (OR = 6.00, 95%CI = 1.19-30.12), as compared with the CC genotype. In the recessive model, we found that the GG genotype carried a 4.55-fold increased risk to classic Kaposi sarcoma as compared with the CC + CG genotype (OR = 2.06, 95%CI = 1.04-20.29). In conclusion, our study demonstrated that miR-146a, but not miR-149 polymorphism, is associated with risk to classic Kaposi sarcoma in the Chinese population.
Ziarkiewicz-Wróblewska B, Suchacz MM, Zieniewicz K, et al. Generalized Posttransplant Kaposi Sarcoma without Mucocutaneous Manifestations in the First Liver Transplantation in an HIV-Positive Patient in Poland: A Case Report and Review of Literature. Ann Transplant. 2016; 21:683-688 [PubMed] Related Publications
BACKGROUND Kaposi sarcoma (KS) is the most frequent skin cancer in solid organ recipients, and also a typical malignancy in HIV-infected persons. CASE REPORT We describe here a rare case of primary nodal KS without mucocutaneous manifestations, diagnosed in a 20-year-old HIV/HBV co-infected patient 12 months after liver transplantation (LT), the first one performed in a HIV-positive patient in Poland. The course of the disease was very aggressive; the patient died four weeks after general lymphadenopathy appearance. In the autopsy, KS infiltration was found in numerous lymph nodes and in the lung' apexes without skin or other organs' involvement. CONCLUSIONS In conclusion, posttransplant KS may present as general lymphadenopathy without mucocutaneous manifestations, thus mimicking posttransplant lymphoproliferative disorder, which is often the first clinical suspicion. Lymph node histopathological examination is necessary to make the right diagnosis.
Tsao MN, Sinclair E, Assaad D, et al. Radiation therapy for the treatment of skin Kaposi sarcoma. Ann Palliat Med. 2016; 5(4):298-302 [PubMed] Related Publications
OBJECTIVE: Kaposi sarcoma (KS) lesions are purplish, reddish blue or dark brown/black macules, plaques or nodules which involve the skin and occasionally internal organs. Most patients with KS have a long indolent chronic course. METHODS: A retrospective review was undertaken for all KS skin patients treated with radiotherapy at a tertiary cancer centre from Jan. 2, 1999 to Dec. 31, 2014 (inclusive). RESULTS: A total of 47 patients with KS (43 classical, 0 African, 1 iatrogenic, 3 AIDS related) were seen in the multidisciplinary clinic. Out of this group, 17 patients (5 females and 12 males, 14 classical, 0 African, 0 iatrogenic, 3 AIDS related) with 97 KS skin sites were treated with local external beam radiotherapy. An additional 18 skin sites were treated with repeat radiotherapy. The radiotherapy dose ranged from 6 Gy in 1 fraction to 30 Gy in 10 fractions with the most common dose fractionation scheme being 8 Gy in 1 fraction or 20 Gy in 5 daily fractions. For the previously untreated KS sites, 87% responded to radiation [30% complete response (CR) and 57% partial response (PR)]. Thirteen percent of KS sites treated with radiation progressed. For the skin sites which were treated with repeat radiotherapy, 0% showed CRs, 50% PRs and 50% had continued progression. CONCLUSIONS: The majority of KS skin lesions (87%) responded to radiotherapy. Patients experience minimal side effects from the palliative radiation regimens used. KS skin lesions which progress despite radiation are unlikely to show CR with repeat radiotherapy. In our experience 50% of skin KS will have partial regression with repeat radiotherapy and 50% will have continued progression.
Lee S, Jang J, Jeon H, et al. Latent Kaposi's sarcoma-associated herpesvirus infection in bladder cancer cells promotes drug resistance by reducing reactive oxygen species. J Microbiol. 2016; 54(11):782-788 [PubMed] Related Publications
Kaposi's sarcoma-associated herpesvirus (KSHV) is the major etiologic agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. Recent studies have indicated that KSHV can be detected at high frequency in patient-derived bladder cancer tissue and might be associated with the pathogenesis of bladder cancer. Bladder cancer is the second most common cancer of the genitourinary tract, and it has a high rate of recurrence. Because drug resistance is closely related to chemotherapy failure and cancer recurrence, we investigated whether KSHV infection is associated with drug resistance of bladder cancer cells. Some KSHV-infected bladder cancer cell lines showed resistance to an anti-cancer drug, cisplatin, possibly as a result of down-regulation of reactive oxygen species. Additionally, drug resistance acquired from KSHV infection could partly be overcome by HDAC1 inhibitors. Taken together, the data suggest the possible role of KSHV in chemo-resistant bladder cancer, and indicate the therapeutic potential of HDAC1 inhibitors in drug-resistant bladder cancers associated with KSHV infection.
Urbanowicz M, Kutzner H, Riveiro-Falkenbach E, Rodriguez-Peralto JL Infectious Angiogenesis-Different Pathways, the Same Goal. Am J Dermatopathol. 2016; 38(11):793-801 [PubMed] Related Publications
Infectious angiogenesis is the biological response of neoangiogenesis induced by infectious organisms. The authors present 3 exemplary entities which show paradigmatic clinico-pathological settings of infectious angiogenesis: Bacillary angiomatosis, Orf (ecthyma contagiosum), and Kaposi sarcoma. The authors review the literature and elucidate etiopathogenetic pathways leading to the phenomenon of neovascularization stimulated by infectious organisms. The authors describe the clinical and histological pictures, interactions between microorganisms and host cells, and changes that occur within cellular structures, as well as angiogenic factors that underpin infectious angiogenesis. The importance of chronic inflammation and tumor angiogenesis is emphasized.
Salihi SA, Buryanek J, Rios AA, Brown RE Morphoproteomics Identifies Etiopathogenetic Correlates of HHV-8-Associated Kaposi's Sarcoma and Provides Pathways with Therapeutic Options: A Case Study. Ann Clin Lab Sci. 2016; 46(5):537-43 [PubMed] Related Publications
A morphoproteomic analysis was performed to identify the proteins and corresponding molecular pathways activated for a case of non-HIV Kaposi's sarcoma. This analysis provides insight into the biology of the tumor and identifies etiopathogenetic correlates of HHV-8-Associated Kaposi's sarcoma that are useful in formulating therapeutic alternatives.
Croteau SE, Gupta D The clinical spectrum of kaposiform hemangioendothelioma and tufted angioma. Semin Cutan Med Surg. 2016; 35(3):147-52 [PubMed] Related Publications
Kasposiform hemoangioendothelioma (KHE) and tufted angioma (TA) are classifed as vascular tumors with locally aggressive and benign growth potential, respectively, within the classification schema proposed by the International Society for the Study of Vascular Anomalies. A unique feature of these vascular tumors is the risk of Kasabach-Merritt phenomenon (KMP), a severe thrombocytopenia with mild to moderate coagulopathy resulting from intralesional platelet trapping. As with many vascular anomalies, accurate description of clinical course, responses to therapy, and long-term outcomes have been hindered by lesion misidentification, imprecise nomenclature, and lack of prospective, randomized clinical trials to assess therapeutic efficacy. The classic dermatologic features of these lesions can facilitate diagnosis for the astute provider; however, the absence of or unusual integumentary involvement or presentation in a less common age group (adolescents/adults) poses a diagnostic challenge. Current approaches to the management of KHE/TA are often informed by lesion features such as presence of KMP, extent and location of the tumor, and symptomatology. Evidence-based treatment guidelines are limited. Corticosteroids, vincristine, interferon, multi-agent regimens and newer therapies, such as sirolimus, have demonstrated efficacy in patient series. The use of surgical excision and interventional radiology guided therapies have been described with mixed clinical benefit. Collaboration among emerging vascular anomaly centers and an increasing number of providers across subspecialties with interest in this field are facilitating the development of standardized approaches to diagnosis and management. The rarity of KHE-spectrum lesions and the heterogeneity of clinical manifestations necessitate rationally designed, multisite clinical trials to investigate risk stratification schemas and formally evaluate the short and long-term efficacy of available and novel therapies.
Karouni M, Kurban M, Abbas O Plasmacytoid dendritic cells in skin lesions of classic Kaposi's sarcoma. Arch Dermatol Res. 2016; 308(7):487-92 [PubMed] Related Publications
Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), which allows them to provide anti-viral resistance and to link the innate and adaptive immunity by controlling the function of myeloid DCs, lymphocytes, and natural killer cells. pDCs are involved in the pathogenesis of several infectious [especially viral, such as Molluscum contagiosum (MC)], inflammatory/autoimmune, and neoplastic entities. Kaposi's sarcoma (KS) is a multifocal, systemic lympho-angioproliferative tumor associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Microscopy typically exhibits a chronic inflammatory lymphoplasmacytic infiltrate in addition to the vascular changes and spindle cell proliferation. Despite the extensive research done on the immune evasion strategies employed by KSHV, pDCs role in relation to KS has only rarely been investigated. Given this, we intend to investigate pDC occurrence and activity in the skin lesions of KS. Immunohistochemical staining for BDCA-2 (specific pDC marker) and MxA (surrogate marker for local type I IFN production) was performed on classic KS (n = 20) with the control group comprising inflamed MC (n = 20). As expected, BDCA-2+ pDCs were present in abundance with diffuse and intense MxA expression (indicative of local type I IFN production) in all inflamed MC cases (20 of 20, 100 %). Though present in all the KS cases, pDCs were significantly less abundant in KS than in inflamed MC cases, and MxA expression was patchy/weak in most KS cases. In summary, pDCs are part of the inflammatory host response in KS; however, they were generally low in number with decreased type I IFN production which is probably related to KSHV's ability to evade the immune system through the production of different viral proteins capable of suppressing IFN production as well as pDC function.
Wong BL, Lee VN, Tikka T, et al. Kaposiform haemangioendothelioma of the head and neck. Crit Rev Oncol Hematol. 2016; 104:156-68 [PubMed] Related Publications
BACKGROUND: Kaposiform haemangioendothelioma (KHE) is a tumor of intermediate malignant potential derived from vascular endothelial cells. Due to rarity of head neck KHE (HN-KHE) this comprehensive review aims to compile, analyze and present details to develop a consensus and augment available literature on HN-KHE. MATERIALS AND METHODS: A comprehensive literature search was performed on PUBMED/MEDLINE, EMBASE, CINAHL and Science Citation Index for HN-KHE using MeSH words. Statistical analysis was performed using a variety of tests. RESULTS: Common sites of involvement were neck 41.5%, face and scalp 32.0% and tympanomastoid region in 13.2% patients. Kasabach-Merritt phenomenon was seen in 58.5% patients. Surgical excision was performed in 37.7% patients while 39.6% patients underwent medical management/chemotherapy (CT). Significantly better disease free survival (DFS) was seen in patients undergoing surgical excision vs. CT (p=0.001), without recurrence vs. with recurrence (p=0.001) and those presenting within 0-1year of life vs. 1-5 years (p=0.021). CONCLUSION: Recurrence and metastasis were seen in 35.8% and 20.0% patients respectively. Complete surgical excision with clear margins remains the treatment of choice.
Papanastasopoulos P, Annan B, Dalla Pria A, Bower M HIV-related Kaposi's Sarcoma with Musculoskeletal Involvement in the Modern Antiretroviral Era. Anticancer Res. 2016; 36(7):3465-9 [PubMed] Related Publications
AIM: To describe the patterns of disease and clinical outcomes of MSK-KS in people living with HIV in the era of (combination anti-retroviral therapy cART). PATIENTS AND METHODS: We reviewed our prospectively collected dataset of patients with HIV with biopsy-proven KS; 17 out of 1,489 seropositive patients were identified with subsequent evidence of MSK involvement by KS. We collected data with regards to clinicopathological parameters and radiological patterns of disease. RESULTS: Fourteen patients (82.4%) had AIDS Clinical Trials Group T1 stage disease at presentation including four (23.5%) with non-nodal visceral disease. At the time of MSK-KS diagnosis, more than 80% of 14 patients had excellent HIV control. The median interval between initial KS to MSK-KS diagnosis was 3.3 years. Five-year overall survival rate from initial KS diagnosis was 76%, and 60% from MSK-KS diagnosis. The majority of patients were asymptomatic and MSK-KS involvement was demonstrated during imaging prompted by progression of their mucocutaneous KS. The majority of lesions were lytic with cortical involvement on cross-sectional imaging, whereas a soft-tissue component was commonly associated with long-bone involvement. CONCLUSION: MSK-KS continues to be a rare entity in the modern era of cART, however patients appear to experience significantly improved survival.
Shabtaie SA, Wang B, Owyong M, et al. Neonatal kaposiform hemangioendothelioma of the spleen associated with Kasabach-Merritt phenomenon. J Pediatr Surg. 2016; 51(6):1047-50 [PubMed] Related Publications
Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor that usually manifests during early childhood. Typically the lesion presents with skin, soft tissue and bone involvement and is characterized histologically by ill-defined nodularity and the presence of spindle cells with resemblance to Kaposi's sarcoma. We report a rare neonatal case of a splenic kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon that was diagnosed with radiographic imaging. Because of the rapid onset of thrombocytopenia and anemia, the patient required urgent splenectomy with subsequent resolution of the blood dyscrasias.
Manciuc C, Filip-Ciubotaru F, Badescu A, et al. THE PATIENT-DOCTOR-PSYCHOLOGIST TRIANGLE IN A CASE Of SEVERE IMUNOSUPRESSION IN THE HIV INFECTION. Rev Med Chir Soc Med Nat Iasi. 2016 Jan-Mar; 120(1):119-23 [PubMed] Related Publications
In the last two years the Romanian adult population infected with the human immunodeficiency virus (HIV) has increased due to sexual transmission, both heterosexual and homosexual. The case presented is that of a 33 year-old man, admitted to the Infectious Diseases Hospital in Iasi with acute respiratory failure and a confirmation of Kaposi's sarcoma. Tests later proved positive for HIV, the patient being included in the stage AIDS C3 (acute immunodeficiency syndrome). The respiratory failure was suspected to be caused by Pneumocystis carinii and cotrimoxazol therapy, oxygen therapy and anti-retroviral therapy were established. He was also referred to the oncology hospital for treatment of Kaposi's sarcoma. The patient's adherence to therapy was influenced by a strong doctor-patient relationship, as well as by psychological counseling and support. Creating a functional doctor-patient-psychologist team is key throughout the HIV-positive patient's existence, for supporting long term adherence to therapy and acceptance of the diagnosis. This case highlights the need for a strong psychosocial compartment in every medical center that deals with HIV-infected individuals.
De Paoli P, Carbone A Kaposi's Sarcoma Herpesvirus: twenty years after its discovery. Eur Rev Med Pharmacol Sci. 2016; 20(7):1288-94 [PubMed] Related Publications
Twenty years after the discovery of Kaposi's Sarcoma Herpes Virus (KSHV), many aspects of the pathogenesis have been discovered and innovative approaches are presently applied to the diagnosis and treatment of KSHV associated diseases. The virus is coupled to different types of cancers, as well as to syndromes combined with increased inflammatory response or with immunoreconstitution in immunocompromised hosts. The etiopathological diagnosis of KSHV associated cancers relies on the demonstration of the virus in tumor samples, as well as in the peripheral blood of infected subjects. Novel treatment strategies related to the pathogenetic events of KSHV associated diseases have been recently studied, that are based on drugs able to induce oncolysis by promoting a viral lytic phase or on the blockade of v-IL6, a cytokine with tumor promoting activities. In addition, antiangiogenetic strategies have also been applied to treat KSHV associated cancers. Despite these important discoveries, some aspects of KSHV associated diseases are presently not completely clear and, consequently, response to treatment strategies is still suboptimal.
Kato H, Yanagisawa N, Morioka H, et al. Laryngeal Kaposi's Sarcoma Complicated by the Immune Reconstitution Inflammatory Syndrome in an HIV-infected Patient. Intern Med. 2016; 55(8):1001-5 [PubMed] Related Publications
We herein report a case of laryngeal Kaposi's sarcoma (KS) complicated by immune reconstitution inflammatory syndrome in a human immunodeficiency virus (HIV)-infected patient. The patient initially presented with KS involving the larynx, which was successfully treated with pegylated liposomal doxorubicin (PLD) and antiretroviral therapy (ART). PLD was discontinued after 2 courses because of a marked clinical improvement; however, the patient experienced progressive odynophagia and dyspnea 2 months after the initiation of ART. Laryngoscopy revealed a severely swollen, inflamed epiglottis. The readministration of PLD was successful, and the patient was thereafter discharged without any subsequent complications.
El-Mallawany NK, Kamiyango W, Slone JS, et al. Clinical Factors Associated with Long-Term Complete Remission versus Poor Response to Chemotherapy in HIV-Infected Children and Adolescents with Kaposi Sarcoma Receiving Bleomycin and Vincristine: A Retrospective Observational Study. PLoS One. 2016; 11(4):e0153335 [PubMed] Free Access to Full ArticleRelated Publications
Kaposi sarcoma (KS) is the most common HIV-associated malignancy in children and adolescents in Africa. Pediatric KS is distinct from adult disease. We evaluated the clinical characteristics associated with long-term outcomes. We performed a retrospective observational analysis of 70 HIV-infected children and adolescents with KS less than 18 years of age diagnosed between 8/2010 and 6/2013 in Lilongwe, Malawi. Local first-line treatment included bleomycin and vincristine plus nevirapine-based highly active anti-retroviral therapy (HAART). Median age was 8.6 years (range 1.7-17.9); there were 35 females (50%). Most common sites of presentation were: lymph node (74%), skin (59%), subcutaneous nodules (33%), oral (27%), woody edema (24%), and visceral (16%). Eighteen (26%) presented with lymphadenopathy only. Severe CD4 suppression occurred in 28%. At time of KS diagnosis, 49% were already on HAART. Overall, 28% presented with a platelet count < 100 x 109/L and 37% with hemoglobin < 8 g/dL. The 2-year event-free (EFS) and overall survival (OS) were 46% and 58% respectively (median follow-up 29 months, range 15-50). Multivariable analysis of risk of death and failure to achieve EFS demonstrated that visceral disease (odds ratios [OR] 19.08 and 11.61, 95% CI 2.22-163.90 and 1.60-83.95 respectively) and presenting with more than 20 skin/oral lesions (OR 9.57 and 22.90, 95% CI 1.01-90.99 and 1.00-524.13 respectively) were independent risk factors for both. Woody edema was associated with failure to achieve EFS (OR 7.80, 95% CI 1.84-33.08) but not death. Univariable analysis revealed that lymph node involvement was favorable for EFS (OR 0.28, 95% CI 0.08-0.99), while T1 TIS staging criteria, presence of cytopenias, and severe immune suppression were not associated with increased mortality. Long-term complete remission is achievable in pediatric KS, however outcomes vary according to clinical presentation. Based on clinical heterogeneity, treatment according to risk-stratification is necessary to improve overall outcomes.
BACKGROUND: Kaposi's sarcoma (KS) is a tumor formed by angioproliferations driven by Human herpes virus 8 also known as Kaposi's sarcoma-associated herpes virus (KSHV). It is best known as an acquired immune deficiency syndrome (AIDS) defining illness that may be fatal. There are only a few reports of KS after hematopoietic cell transplantation (HCT). This is the first case describing the disappearance of KS with immune recovery after autologous HCT. CASE PRESENTATION: We present the case of a 61-year-old male heterosexual patient of Moroccan origin treated for primary mediastinal non-Hodgkin lymphoma. Because of refractory disease he received multiple lines of chemotherapy prior to autologous HCT. After the second course of low-dose bis-chloroethylnitrosourea, etoposide, cytarabine, melphalan (BEAM) the patient developed several round blue skin lesions. A biopsy was performed, showing many small vessels and positive immune histochemical staining for Human herpes virus 8 (HHV-8), confirming diagnosis of KS. Human immunodeficiency virus testing was negative and work-up showed that there were no visceral lesions. When KS are limited to the skin, prognosis is usually better. The extensive chemotherapy resulted in an important immunosuppression; on day 105 after autologous HCT CD4(+) count was 82/mm(3). Since KS were limited to the skin and attributed to severe immune suppression a watchful waiting strategy was adopted even though in the first months after autologous HCT new skin lesions appeared. With immune recovery (CD4(+) count > 200/mm(3)) 277 days after transplant, skin lesions faded. CONCLUSION: Kaposi's sarcoma remains a rare tumor that should be thought of in any patient whose immunity is down. If immune recovery is expected and disease is limited to the skin, a watchful waiting strategy can be more rewarding than intensive chemotherapy.
Hu L, Wang K, Wang Z, et al. A New Megastigmane Sesquiterpenoid from Zanthoxylum Schinifolium Sieb. et Zucc. Molecules. 2016; 21(3):383 [PubMed] Related Publications
Zanthoxylum schinifolium Sieb. et Zucc. (Rutaceae), a dioecious shrub with hooked prickly branches, has been used as folk medicine for the treatment of the common cold, stomach ache, diarrhea, and jaundice in China, Korea, and Japan. In our phytochemical investigations on this genus, a new megastigmane sesquiterpenoid, which is referred to as schinifolenol A (1), was isolated from Z. schinifolium. The stereochemistry was characterized via the analyses of extensive spectra. The absolute configuration was established by the application of a modified Mosher's experiment and assisted by a time-dependent density functional theory (TD-DFT) on calculated electronic circular dichroism (ECD). Bioactivity screenings showed that compound 1 exhibited a safe hypotoxicity and a better selectivity on anti-Kaposi's sarcoma associated herpes virus (KSHV).
Mohan P, Yuvaraj A, Abraham G, et al. Occurrence of double primary malignancies in an African renal transplant recipient. Saudi J Kidney Dis Transpl. 2016; 27(2):377-80 [PubMed] Related Publications
A 63-year-old African male with end stage renal disease who received a renal transplantation from his daughter after successful treatment of hepatitis C virus, type 1 genotype developed metastatic Kaposi's sarcoma and subsequently adenocarcinoma of the prostate. He was successfully treated with chemotherapy and reduction of immunosuppression and switch over to rapamycin.
Broccolo F, Tassan Din C, Viganò MG, et al. HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi's sarcoma. J Clin Virol. 2016; 78:47-52 [PubMed] Related Publications
BACKGROUND: The value of plasma levels of human herpesvirus 8 (HHV-8) DNA as a marker of clinical status in acquired immunodeficiency syndrome-related Kaposi's sarcoma (AIDS-KS) remains to be elucidated. OBJECTIVES: To investigate the relationship between the plasma HHV-8 DNA viral load and the clinical status of AIDS-KS. STUDY DESIGN: A total of 378 blood samples were obtained from 62 patients with AIDS-KS followed longitudinally. All patients received antiretroviral therapy (ART) or anti-neoplastic therapy. The patients were divided into four groups according to their clinical status: onset disease (OD), progressive disease (PD), stable or partial remission (S/PR) and complete remission (CR). RESULTS: Plasma HHV-8 DNAaemia was detected in all samples obtained from patients with OD or PD (100%); in contrast, HHV-8 DNAaemia was found only in a minority of patients with CR (8%) and was invariably undetectable in patients with stable CR. HHV-8 DNA detection in plasma was strongly associated with an unfavourable outcome (odds ratio=231.9; p<0.0001). Conversely, neither the HIV-1 viral load nor peripheral CD4(+) T-cell counts were associated with the KS clinical status, though both parameters did affect HHV-8 DNAaemia levels (p<0.0001). Multivariate analysis confirmed that HHV-8 DNAaemia was strongly and independently correlated with both clinical status (p<0.05) and HIV-1 plasma viraemia (p=0.027). CONCLUSIONS: The strong association of plasma HHV-8 DNAaemia with onset or progressive disease is compatible with an active role of replicating virus in clinically active AIDS-KS. An accurate evaluation of the plasma HHV-8 load might be useful for monitoring AIDS-KS under antiretroviral or antineoplastic therapy.
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (ΔmiR-K12-1 through -12), and for mutants deleted for 10 of 12 (ΔmiR-cluster) or all 12 miRNAs (ΔmiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community.
BACKGROUND: As global population of the elderly continues to rise, a critical need to provide it with health services, including dermatology, will be significant, especially in developing countries like Tanzania. To adequately meet their dermatologic needs, knowledge of local patterns of skin conditions is vital. This study was aimed to describe the spectrum of skin diseases among elderly patients attending skin clinic at the Regional Dermatology Training Centre (RDTC) in Northern Tanzania. METHODS: A descriptive hospital based cross-sectional study was conducted between January 2013 and April 2013 at RDTC and included all patients aged 55 years and above who consented to be examined. Diagnoses were clinical, diagnostic tests being done only when necessary. Ethical clearance to conduct the study was granted. RESULTS: A total of 142 patients, age ranges 55-99 years, median age of 67.5 years were seen. Eczemas were the leading disease group (43.7%), with unclassified eczemas (33.9%) predominating. Papulosquamous disorders (15.4%) were second with psoriasis (50%) being the leading disease. Infections (11.3% with fungal infections the leading group representing 5.6% of all diseases), tumours (9.8%: Kaposi's sarcoma 4.2%), vascular disorders 9.1% (lymphedema 4.9%), autoimmune disorders 7.7% (connective tissue diseases 4.9%), vitiligo 4.2%, nutritional diseases 2.1% (pellagra 0.7%), urticaria 0.7% and drug reactions 0.7%. CONCLUSIONS: Eczemas are the most common group of disorders among elderly patients presenting at RDTC.
Hacioglu MB, Sahin S, Karatas F, Aytekin A A rare coexistence--Chronic lymphocytic leukemia and Kaposi sarcoma: Case report and review of the literature. J Cancer Res Ther. 2015 Oct-Dec; 11(4):954-6 [PubMed] Related Publications
Chronic lymphocytic leukemia (CLL) is the most common leukemia worldwide. Skin lesions associated with CLL mostly develop on the bases of infectious or a hemorrhagic origin with an estimated incidence of 25% of all the cases. Kaposi sarcoma (KS)-associated with human herpes virus-8 infection is a spindle-cell, malignant, low-grade tumor originating from vascular and lymphatic endothelium. KS mostly presents with skin lesions as the initial presentation. The relation between these two pathologies has not yet been clarified up to date. Herein, we report a case of KS along with CLL to illustrate the possible relation between these two pathologies.
Dong A, Zhang L, Wang Y, et al. Abdominal Kaposiform Hemangioendothelioma Associated With Lymphangiomatosis Involving Mesentery and Ileum: A Case Report of MRI, CT, and 18F-FDG PET/CT Findings. Medicine (Baltimore). 2016; 95(6):e2806 [PubMed] Free Access to Full ArticleRelated Publications
Kaposiform hemangioendothelioma (KH) is a rare vascular tumor of intermediate malignancy that occurs mainly in the childhood. Adult patients with KH are rare. Imaging findings of KH have rarely been reported before. We present magnetic resonance imaging (MRI), computed tomography (CT), and fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/CT findings in an adult patient with KH associated with lymphangiomatosis involving mesentery and ileum.A 22-year-old female complained of a 9-month history of intermittent melena, weakness, and palpitation. Laboratory tests revealed anemia and hypoproteinemia. Fecal occult blood test was positive. Abdominal enhanced MRI and CT showed a large abdominal mass involving mesentery and ileum. On enhanced MRI, there were many hypervascular nodules in the mass. On FDG PET/CT, the mass and the nodules showed slight FDG uptake. Small bowel capsule endoscopy showed numerous grape-shaped red nodules in the luminal wall of the involved ileum. The patient underwent resection of the abdominal mass and a segment of the ileum invaded by the abdominal mass. KH arising within lymphangiomatosis involving mesentery and ileum was confirmed by pathology. After surgery, the patient's symptoms improved.This is the first case of KH associated with lymphangiomatosis involving mesentery and ileum. In this case, the lymphangiomatosis overshadowed the small tumor nodules resulting in unusual imaging findings. Familiarity with these imaging findings is helpful for diagnosis and differential diagnosis of KH.
Oza VS, Mamlouk MD, Hess CP, et al. Role of Sirolimus in Advanced Kaposiform Hemangioendothelioma. Pediatr Dermatol. 2016 Mar-Apr; 33(2):e88-92 [PubMed] Related Publications
Kaposiform hemangioendothelioma (KHE) is an infiltrative vascular tumor that classically presents in infancy. Management typically focuses on treating Kasabach-Merritt phenomenon (KMP), a disorder of severe and at times life-threatening platelet trapping. However, the morbidity of KHE extends beyond KMP. The infiltrative nature of the tumor can lead to long-term disability and often makes complete surgical resection impossible. We report the case of a 10-year-old boy with a KHE of his right distal thigh who was unable to walk without assistance due to fibrotic change and right knee contracture. He had no laboratory evidence of KMP at the time of representation. Rapamycin was started in hopes of reducing the tumor burden. Within 2 months of therapy, fibrotic areas softened, his contracture nearly resolved, and there was marked improvement in his mobility. Rapamycin has been previously reported to be effective in managing cases of KHE complicated by KMP. Our report emphasizes the role for rapamycin in the treatment of KHE in the absence of KMP through the inhibition of vasculogenesis and fibrotic pathways.
Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly elevated in both CD147-overexpressing and KSHV-infected HUVEC cells when compared to control cells. In the current study, we further identify the regulation of HO-1 expression and mediated cellular functions by both CD147 and KSHV-encoded LANA proteins. Targeting HO-1 by either RNAi or the chemical inhibitor, SnPP, effectively induces cell death of KSHV-infected endothelial cells (the major cellular components of KS) through DNA damage and necrosis process. By using a KS-like nude mouse model, we found that SnPP treatment significantly suppressed KSHV-induced tumorigenesis in vivo. Taken together, our data demonstrate the important role of HO-1 in the pathogenesis and tumorigenesis of KSHV-infected endothelial cells, the underlying regulatory mechanisms for HO-1 expression and targeting HO-1 may represent a promising therapeutic strategy against KSHV-related malignancies.
Freeman E, Semeere A, Wenger M, et al. Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa. BMC Cancer. 2016; 16:65 [PubMed] Free Access to Full ArticleRelated Publications
BACKGROUND: Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS: We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS: Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS: In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited.
Gupta V, Patra S, Arava S, Sethuraman G Hidden acral lentiginous melanoma with cutaneous metastases masquerading as Kaposi's sarcoma in an HIV-positive Indian man. BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 33-year-old HIV-positive Indian man presented with multiple bluish and erythematous papulo-nodules on his right leg and foot. A diagnosis of Kaposi's sarcoma was suspected clinically. Biopsy of the cutaneous lesions showed features of melanoma. On careful re-examination, an irregular brown-black macule, of which the patient was unaware, was noted on the ipsilateral sole. Histological examination of the sole lesion also showed features of melanoma. Systemic evaluation revealed extensive nodal and visceral metastases.
Epelbaum O, Go R, Patel G, Braman S Pulmonary Kaposi's Sarcoma and Its Complications in the HAART Era: A Contemporary Case-Based Review. Lung. 2016; 194(1):163-9 [PubMed] Related Publications
The early years of the acquired immunodeficiency syndrome (AIDS) epidemic introduced the global medical community to Kaposi's sarcoma (KS), a heretofore seldom encountered angiosarcomatous neoplasm associated with human herpesvirus-8. At that time, clinicians treating these KS patients were routinely exposed to the pulmonary manifestations of this malignancy, including characteristic airway lesions, peribronchovascular opacities, and the typically hemorrhagic pleural effusions. They also witnessed uncommon complications of pulmonary KS such as chylous effusions, diffuse alveolar hemorrhage, and immune reconstitution inflammatory syndrome. Since the advent of highly active antiretroviral therapy, the incidence of KS has steadily declined and with that so has clinician familiarity with this disease. Herein, we present four KS cases recently encountered at our institution that illustrate both typical manifestations of pulmonary KS as well as its thoracic complications. The case descriptions are followed by a review of these clinical entities with the aim of restoring awareness among frontline physicians of what is now a rare but not quite extinct AIDS-defining neoplasm.
In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count >350 cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence.
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