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PubMed2004

[Localization and clinical characteristics of the ocular metastases of solid extraocular tumours].

Localization and clinical characteristics of the ocular metastases of solid tumours are presented. Choroid is the most common localization site of these metastases, however they may involve each ocular structure. In the most cases they are diagnosed in patients with earlier recognized cancer, but in 12-40% of the patients ocular metastasis is a first sign of the neoplasm. Therapy is focused to save the eye function or last but not least to improve patient's status.

Breast Neoplasms↗

PubMed2001

Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases.

BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment. CASE REPORT: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. Growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital. CASE REPORTS IN THE LITERATURE: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose. CONCLUSIONS: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.

Adolescent↗

PubMed2000

Photodynamic therapy for residual neoplasms of the perianal skin.

PURPOSE: The aim of this study was to evaluate the efficacy of photodynamic therapy in the management of residual neoplasms of the perianal skin. METHODS: This is a retrospective review. Five patients with pathologic confirmation of residual perianal neoplasms were treated with photodynamic therapy. There were three females. The mean age was 52 (range, 33-79) years. Pathology consisted of Bowen's disease in two patients, squamous-cell carcinoma in two patients, and extramammary Paget's disease in one patient. Four patients received one photodynamic therapy treatment and one patient received two treatments three months apart. RESULTS: Treatment was followed by immediate perianal erythema, subsequent blister formation in 36 to 48 hours, and sloughing of the treated area in 72 hours. With a mean follow-up of 5.2 (range, 1-8) years, there were two recurrences. One recurrence was in a patient four years after treatment for Paget's disease, and the other was in a patient nine months after treatment for Bowen's disease. The latter was managed successfully with wide local excision. Treatment-related toxicities included significant perianal pain in four patients, controlled with analgesia management. CONCLUSIONS: Photodynamic therapy can successfully be used after wide local excision for residual neoplasms of the perianal skin. Treatment can be rendered with acceptable morbidity.

Adult↗

PubMed2026

Genomic Evolution of Myeloproliferative Neoplasms and Therapy-Associated Mutagenesis.

UNLABELLED: Philadelphia-negative myeloproliferative neoplasms are chronic blood neoplasms. Treatments control blood counts, but disease can progress to myelofibrosis or acute myeloid leukemia. We performed longitudinal whole-genome and targeted sequencing in 30 patients, integrating clonal dynamics with 7,986 blood counts and clinical histories. Distinct evolutionary patterns distinguished stable from progressive disease, with leukemic transformation arising via TP53 loss, stepwise driver mutation acquisition within complex clones, or emergence of independent leukemic clones. In contrast, stable disease showed long-term clonal equilibrium without new drivers. Phylogenetic analysis using 203 whole-genomes of hematopoietic colonies revealed age-appropriate polyclonal hematopoiesis in triple-negative essential thrombocythemia and germline predisposition to thrombocytosis, supporting non-neoplastic origins. Therapy-associated mutagenesis was observed, including C > G mutations following azacitidine and characteristic T > A/T > G after hydroxycarbamide exposure in blood cells, although not in skin where UV damage predominated. These findings demonstrate that progression is genomically encoded years in advance and support serial monitoring and further study of treatment-related mutagenesis. SIGNIFICANCE: Longitudinal whole-genome sequencing shows MPN progression is genomically encoded years before clinical transformation, with distinct evolutionary routes to leukemia and MF. It identifies DNA mutagenesis associated with HC and 5-azacitidine, suggests some triple-negative cases are nonclonal, and supports serial clinical genomic monitoring for improved risk stratification and long-term management. See related commentary by Agarwal and Sankaran, p. 1724.

Humans↗

PubMed1979

[Prevention of thrombosis during therapy of gynecologic neoplasms].

Blood coagulation, but especially diagnosis, prophylaxis and therapy of thromboembolic complications are of special importance in gynaecology. Besides connatal factors acquired factors are to be considered. Carcinomas enhance hypercoagulation, especially if x-ray treatment is performed. There exists a great number of diagnostic and therapeutic possibilities, though adequate prophylaxis is much more efficient than extensive diagnosis. Among the many possibilities of prophylaxis of thromboembolic complications the subcutaneous application of heparin in subclinical doses is especially efficient. Application is simple, paractically painless, additionally healing is enhanced by heparin.

Coumarins↗

PubMed1995

[Effect of intravenous treatment with tumor necrosis factor alpha in patients with advanced cancer--phase I clinical trials].

Tumor necrosis factor (TNF) is the protein produced by the activated macrophages with the ability to produce haemorrhagic necrosis of tumor, and in some cases complete tumor remission in vivo, as well as cytotoxicity of neoplastic cells in vitro. These properties made us undertake clinical studies on THF. We performed a Phase I assessment of recombinant human THF alpha in 16 patients with advanced solid neoplasms. Therapy consisted of a 30 minute intravenous (IV) infusion on day i thraugh 5, every 2 weeks. Daily doses ranged from 25 micrograms/m2 to 200 micrograms/m2. Side effects hypotension tachycardia nausea or vomiting, headache. No major changes in liver or renal function were seen.

Adult↗

PubMedDate not supplied

Photodynamic therapy for intracranial neoplasms. Literature review and institutional experience.

Primary malignant glial neoplasms of the central nervous system have a dismal 2-yr prognosis. An innovative approach to these formidable lesions is photodynamic therapy that employs a chemotherapeutic photosensitizing agent in combination with wavelength specific light to produce cytotoxic reactions capable of destroying neoplastic tissues. Animal and initial clinical studies of the application of photodynamic therapy to intracranial neoplasms have been promising. Parameters to optimize the efficacy of this treatment are under investigation. A review of the preclinical and clinical studies of photodynamic therapy for intracranial neoplasms is described.

Animals↗

PubMed2005

Mutant IkappaBalpha suppresses hypoxia-induced VEGF expression through downregulation of HIF-1alpha and COX-2 in human glioma cells.

Our previous study demonstrated that mutant IkappaBalpha (IkappaBalphaM) could inhibit glioma angiogenesis and tumorigenesis through the downregulation of vascular endothelial growth factor (VEGF) and IL-8. However, the pathways involved in VEGF expression are not well understood. Growing evidence indicates that hypoxia-inducible factor-1alpha (HIF-1alpha) and cyclooxygenases-2 (COX-2) play important roles in this progression. In this study, we first examined the expressions of hypoxia-induced genes in human glioma cells transfected with IkappaBalphaM (IN500deltaM) or control plasmid (IN500delta) in vitro. We found that hypoxic stress induced the expressions of HIF-1alpha, COX-2, and VEGF, and that IkappaBalphaM completely suppressed these expressions in vitro. Next, we injected these glioma cells into nude mice. After 3 weeks, the mice were moved to a hypoxic chamber (10% oxygen) for 3, 12, 24, 48, 96, or 144 h. The expressions of HIF-1alpha, COX-2, and VEGF in vivo were then analyzed by Northern blot and immunohistochemistry. IkappaBalphaM suppressed the expression of hypoxia-induced HIF-1alpha gene in vivo, but hypoxic stress induced the expression of COX-2 after 72 h. VEGF induction followed after 96 h of hypoxia in IN500deltaM cells. These findings suggest that VEGF expression appears to be regulated through dual interdependent mechanisms involving HIF-1 and COX-2 genes, and IkappaBalphaM could inhibit VEGF expression through these two pathways. Thus, IkappaBalphaM is identified as a pivotal factor in angiogenesis and is a potential target for neoplasm therapy.

Animals↗

PubMed2002

Effects of lithium carbonate on hematopoietic cells in patients with persistent neutropenia following chemotherapy or radiotherapy.

Neoplasm therapy is restricted by the haematological side effects of tumour-destructive therapy, requiring expensive supportive care to some extent to overcome and treat leucopenia and its consequences. An effective and very cost-effective alternative for treating neutropenia is to administer lithium carbonate. Lithium leads to a release of hematopoietic growth factors (CSF) and therefore to proliferation of neutrophil granulocytes. Normally, recombinant CSF is only administered when there are indications of severe neutropenia because of the high costs involved, all the more evident in the long-term treatment of persistent leucocytopenia. On the other hand, CSF and leucocytes play an essential role in tumour immunology and with regard to response rates to cytostatic drugs. Lithium salts have shown that they can increase the number of neutrophil granulocytes quite significantly and, to a lesser extent, the number of eosinophil granulocytes and lymphocytes as well. The average number of erythrocytes does not change significantly. Patient tolerability to lithium carbonate therapy is very good. It can be used to treat patients with chronic leucopenia following chemotherapy or radiotherapy extremely cost-effectively. Unfortunately this treatment has not won acceptance in clinical oncology in the face of highly cost-intensive treatment with recombinant CSF.

Adult↗

PubMed2004

Testicular function following chemo-radiotherapy.

Improvements in cancer survival raise infertility issues in young patients suffering from malignancies. The aim of the study is to review current knowledge on the effect of chemotherapy (CT) and radiotherapy (RT) for testis and hematological neoplasms on testicular function. Cisplatin-based regimens for testis neoplasm induce temporary azoospermia; permanent damage can occur with high doses (400-600 mg/m(2)). Alkylating agents are very effective for hematological neoplasm therapy but extremely dangerous to germinal epithelium. Damage can be irreversible. Spermatozoa cannot tolerate irradiation doses higher than 6 Gy. Leydig cells are damaged by doses higher than 15 Gy. A-Spermatogonia have been shown to survive after CT and RT and their recovery for post-treatment graft has been recently developed in animal models. Infertility counselling before treatment in young oncological patients is mandatory. Cryopreservation is the best option for fertility protection.

Animals↗

PubMed1988

A phase I clinical trial of recombinant human tumor necrosis factor.

We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.

Adult↗

PubMed1965