Hepatic Angiosarcoma Post-Renal Transplantation: A Case Report.

BACKGROUND: DNA damage and oncogenic viruses increase the risk of cancer post-kidney transplantation, including skin cancer, Kaposi's sarcoma, oral cancer, and non-Hodgkin lymphoma. Here we report an uncommon case of liver angiosarcoma that occurred 8 years after kidney transplantation. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source. CASE REPORT: A 57-year-old female patient received a cadaver kidney transplantation 8 years ago. She followed a long-term regimen of tacrolimus, mycophenolate sodium, and everolimus, with good renal function. She received annual regular abdominal ultrasound examinations after kidney transplantation, which showed no findings. The patient suffered from several symptoms for approximately 2 weeks before a scheduled abdominal ultrasound: diarrhea, epigastric pain, abdominal fullness, tea-colored urine, and little stool passage. The abdominal computerized tomography showed multiple hepatic tumors in both the hepatic lobes with engorged vasculatures and mild hemoperitoneum. A liver biopsy revealed the histopathology of angiosarcoma. The patient suffered multiple organ failure within one month of treatment. CONCLUSIONS: Various post-transplant malignancies are not uncommon after transplantation, warranting periodic screenings for any symptoms in these patients.

PARP inhibition in UV-associated angiosarcoma preclinical models.

PURPOSE: Angiosarcoma (AS) is a rare vasoformative sarcoma, with poor overall survival and a high need for novel treatment options. Clinically, AS consists of different subtypes, including AS related to previous UV exposure (UV AS) which could indicate susceptibility to DNA damage repair inhibition. We, therefore, investigated the presence of biomarkers PARP1 (poly(ADP-ribose)polymerase-1) and Schlafen-11 (SLFN11) in UV AS. Based on experiences in other sarcomas, we examined (combination) treatment of PARP inhibitor (PARPi) olaparib and temozolomide (TMZ) in UV AS cell lines. METHODS: Previously collected UV AS (n = 47) and non-UV AS (n = 96) patient samples and two UV AS cell lines (MO-LAS and AS-M) were immunohistochemically assessed for PARP1 and SLFN11 expression. Both cell lines were treated with single agents PARPi olaparib and TMZ, and the combination treatment. Next, cell viability and treatment synergy were analyzed. In addition, effects on apoptosis and DNA damage were examined. RESULTS: In 46/47 UV AS samples (98%), PARP1 expression was present. SLFN11 was expressed in 80% (37/46) of cases. Olaparib and TMZ combination treatment was synergistic in both cell lines, with significantly increased apoptosis compared to single agent treatment. Furthermore, a significant increase in DNA damage marker γH2AX was present in both cell lines after combination therapy. CONCLUSION: We showed combination treatment of olaparib with TMZ was synergistic in UV AS cell lines. Expression of PARP1 and SLFN11 was present in the majority of UV AS tumor samples. Together, these results suggest combination treatment of olaparib and TMZ is a potential novel AS subtype-specific treatment option for UV AS patients.

Effect of a combined surgery, re-irradiation and hyperthermia therapy on local control rate in radio-induced angiosarcoma of the chest wall.

PURPOSE: Radiation-induced angiosarcoma (RAS) of the chest wall/breast has a poor prognosis due to the high percentage of local failures. The efficacy and side effects of re-irradiation plus hyperthermia (reRT + HT) treatment alone or in combination with surgery were assessed in RAS patients. PATIENTS AND METHODS: RAS was diagnosed in 23 breast cancer patients and 1 patient with melanoma. These patients had previously undergone breast conserving therapy (BCT, n = 18), mastectomy with irradiation (n=5) or axillary lymph node dissection with irradiation (n = 1). Treatment consisted of surgery followed by reRT + HT (n = 8), reRT + HT followed by surgery (n = 3) or reRT + HT alone (n = 13). Patients received a mean radiation dose of 35 Gy (32-54 Gy) and 3-6 hyperthermia treatments (mean 4). Hyperthermia was given once or twice a week following radiotherapy (RT). RESULTS: The median latency interval between previous radiation and diagnosis of RAS was 106 months (range 45-212 months). Following reRT + HT, the complete response (CR) rate was 56 %. In the subgroup of patients receiving surgery, the 3-month, 1- and 3-year actuarial local control (LC) rates were 91, 46 and 46 %, respectively. In the subgroup of patients without surgery, the rates were 54, 32 and 22 %, respectively. Late grade 4 RT toxicity was seen in 2 patients. CONCLUSION: The present study shows that reRT + HT treatment--either alone or combined with surgery--improves LC rates in patients with RAS.

Association of liver hemangiosarcoma and secondary iron overload in B6C3F1 mice--the National Toxicology Program experience.

The literature evidencing the role of iron in promoting a range of neoplasms in humans and animals prompted us to search for a possible association between chemically induced hemosiderosis and hemangiosarcomas in the liver of mice in selected studies conducted by the National Toxicology Program (NTP). Its historical control database was examined for studies in which treatment-related liver hemangiosarcoma was noted; 130 consecutive NTP studies in B6C3F1 mice from Technical Report (TR)-340 to TR-493 were evaluated. Three compounds (2-butoxyethanol, p-nitroaniline, and para-chloroaniline) were associated with a relatively high incidence of Kupffer cell pigmentation consisting of hemosiderin in both sexes; only the male mice developed a relatively low incidence of treatment-related hemangiosarcoma. With a fourth compound (o-nitroanisole), a relatively low incidence (16/50, high-dose males) of chemical-related hemosiderosis was noted, with no associated increase of hemangiosarcoma. Two chemicals (pentachlorophenol and tetrafluoroethylene) increased the incidence of liver hemangiosarcoma in male and female mice, with no increase in Kupffer cell pigmentation. The overall association between liver hemangiosarcoma and Kupffer cell pigmentation was highly significant (p < 0.001). The cause for hemosiderosis in all cases was the erythrocytic hemolytic effect of the compounds. The reason for the sex-increased susceptibility for development of hemangiosarcoma is unknown but may be due to a hormone-related, reduced antioxidative defensive capacity through modulation of the activities of antioxidative enzymes.

Angiosarcomas radioinducidos / Radioinducted angiosarcomas

Se contribuye a la casuística con la presentación de 2 casos de angiosarcoma radioinducido, diagnosticados ambos, en pacientes de sexo femenino que previamente habían recibido dosis total de radioterapia, uno por presentar un linfoma tipo Hodgkin, y otro por carcinoma ductal de mama. En una de las pacientes el tiempo de latencia fue de 10 años, mientras que en la otra fue de 25 años. La evolución fue dispar, ya que mientras una tiene un año de evolución sin evidencias de enfermedad, la otra falleció debido a metástasis pulmonares y complicaciones cardíacas al año de ser operada

Radiation-induced angiosarcoma of the breast. Case report and review of the literature.

Angiosarcoma is a rare, highly malignant soft tissue sarcoma that sometimes occurs in the breast as a late sequela of treatment for breast cancer. The conventional treatment for radiation-induced angiosarcoma is surgery, which is associated with a poor overall prognosis. We report a case of radiation-induced angiosarcoma of the intact breast that occurred 6 years after breast conservation therapy. Simple mastectomy was performed; however, rapid chest wall recurrence of angiosarcoma ensued. After salvage therapy with combined radiotherapy and hyperthermia, the patient has been disease-free for more than 3 years.

Hepatic haemangiosarcoma in a patient with psoriasis and Crohn's disease.

Hepatic haemangiosarcoma is a rare condition although there are known carcinogens in 25%. This case reports hepatic haemangiosarcoma in a 59 year old man with psoriasis and Crohn's disease who had previously received combined treatment with psoralen and UVA light.