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Mechanical properties of keloids in vivo during treatment with intralesional triamcinolone acetonide.

The mechanical properties of 17 keloids in 9 patients before and during treatment with intralesional triamcinolone acetonide were studied using a recently developed noninvasive suction device for measuring skin elasticity in vivo. Each keloid was treated with intralesional injections of 10 mg/ml triamcinolone acetonide without local anaesthetic at intervals of 3 weeks. A total of four measurements per keloid were performed, before treatment and 3 weeks after the first, second and third treatments. The parameters used were: immediate distension (Ue), delayed distension (Uv), immediate retraction (Ur) and final distension (Uf). Relative parameters independent of skin thickness were calculated: Uv/Ue, the ratio between the viscous and the elastic deformation of the skin, and Ur/Uf, representing the ability of the skin to return to its initial position after deformation (biological elasticity). After three injections of triamcinolone acetonide a marked decrease in Uv/Ue and a less-pronounced increase in Ur/Uf compared with baseline values was observed. These findings indicate that the main effect of intralesional steroids on the connective tissue of keloids is a decrease in viscosity due to a loss of ground substance. This method provides a noninvasive quantitative assessment of the mechanical properties of scars and is well suited to comparative studies on the efficacy of various scar therapies.

Adolescent↗

Interferon alpha in the therapy of conjunctival lymphoma in an HIV+ patient.

The authors evaluated the efficacy of interferon-alpha used intralesionally in the therapy of low-grade conjunctival non-Hodgkin lymphoma in an HIV-positive patient. The patient received one intralesional injection of 1,000,000 U of interferon-alpha three times a week for a total of twelve doses. The remission of conjunctival involvement was seen three months from the end of therapy. The intralesional use of interferon-alpha can be considered an efficacious therapy for low-grade conjunctival non-Hodgkin lymphoma.

Conjunctival Neoplasms↗

Intratumoral immunotherapy with interferon-alpha and interleukin-2 in glioblastoma.

The combination of the cytokines interferon-alpha 2b and rIL-2, at doses of 10 x 10(6) IU and 9 x 10(6) IU, respectively, in a 1.5 cc solution, can be safely injected into cystic glioblastoma without any evidence of side effects or increase in surrounding tumoral oedema. Nevertheless, an immunotherapeutic protocol in ten glioblastoma patients with tumour growth, that consisted of one intralesional injection per week, over 4 weeks of this combination of cytokines, had no effect on tumour progression.

Brain Neoplasms↗

[Minimal invasive therapy of localized Langerhans-cell histiocytosis of bone].

PURPOSE: Scaglietti introduced a method of steroid injection for the management of unicameral bone cysts in 1974. Subsequently the intralesional infiltration of corticosteriods has also been recommended as a primary therapy for localized Langerhanscell histiocytosis (LCH). We report our experience with the administration of methylprednisolone acetate in children and young adults localized LCH. MATERIAL AND METHODS: [corrected] Nine patients with localized LCH, aged 2 3/12 to 29 years, were treated with a single--in only one case two--intralesional injection of methylprednisolone acetate as a crystalline suspension. The dose was between 40 and 150 mg depending on the size of the radiolucent defect. We treated 4 lesions in the skull, 3 in the femur, 1 in the distal humerus and 1 in the mandibula. In each case the diagnosis was established by biopsy. Follow-up ranged from 2 to 8 8/12 years (4 years 4 months on average). RESULTS: 7 out of 9 patients with localized LCH had excellent results with complete healing of the lesion. In 2 patients there was no response to the initial injection therapy and dissemination of the disease occurred. In 4 patients with an additional soft tissue tumor, after injection therapy of the bone lesion, the soft tissue tumor resolved without further treatment. CONCLUSION: Intralesional infiltration of methylprednisolone acetate as a primary therapy for localized Langerhans cell histiocytosis leads to rapid relief of pain, restoration of bone morphology and reduction of associated soft tissue tumors. Performed with appropriate skill under sterile condition with the reported high percentage of effectiveness and low recurrence rate, this low invasive method is the treatment of choice, resulting in a lower morbidity and lower costs.

Adolescent↗

Preliminary experiences of intralesional immunotherapy in cutaneous metastatic melanoma.

BACKGROUND/AIMS: Antigen presenting cells are inactive within tumor tissue because of local immunosuppression. Tumor infiltrating lymphocyte signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor may lead to antigen-presenting cell recovery and interleukin-2 may restore local tumor infiltrating lymphocyte activation. Moreover, interleukin-2 increases the systemic lymphocyte population, an event which seems to correlate with a better prognosis. The present phase I-II study was carried out to examine whether intralesional injection of granulocyte macrophage-colony stimulating factor followed by subcutaneous interleukin-2 would induce a clinical response in advanced, pretreated and elderly melanoma patients. METHODOLOGY: Fourteen patients over 60 years of age received intralesional granulocyte macrophage-colony stimulating factor (150 micrograms per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous interleukin-2 (3.000.000/IU) for 5 days (3 to 7) every 3 weeks. All patients received 6 courses of treatment unless progression occurred. Clinical evaluation of the treated cutaneous lesions was assessed at the baseline and before every cycle. Distant lesions were checked every two cycles. RESULTS: Four clinical responses (2 partial responses and 2 minimal responses) (28.5%), which also involved lesions that had not been directly treated, and seven cases of stable disease were observed. The response duration for partial response and minimal response was 9, 4, 4 and 2.5+ months, respectively. Stable disease (50%) recorded in the 7 patients was short term, 3-6 months. Three patients rapidly progressed after 2, 2, and 1 therapy cycles, respectively. The patient who reached the best partial response had a fairly high absolute lymphocyte count (1600 to 2400/mm3). The second one, who reached a complete remission after subsequent locoregional chemotherapy and hyperthermia, had a low absolute lymphocyte count which had doubled, however, by the end of treatment. Blood lymphocyte values in the other patients were too varied to allow any correlation with clinical response. Therapy was well tolerated and only mild fever was observed, with the exception of one patient who had grade 3 fever, with muscle pain and arthralgia. CONCLUSIONS: Considering the very low toxicity observed, this treatment might be indicated in elderly patients for whom systemic therapy is no longer a viable option. Improved scheduling and timing could result from further studies.

Aged↗

Periocular sarcoid in a horse.

A periocular nodular sarcoid of the right upper and lower eyelids was diagnosed in an 11-year-old Thoroughbred mare. Computed tomography scan revealed the extent of the tumor. The mass was surgically debulked under general anesthesia, and the affected periocular region was injected intralesionally with Bacillus of Calmette and Guerin (BCG). An emulsion of cell wall fractions was used, which has been modified to reduce the toxic and allergic effect, but retain the antitumor activity. In total, five injections were performed at 2-week intervals. At follow-up 7 months after the last BCG injection, the tumor was completely resolved. Two years after the last treatment, the horse remains tumor-free.

Animals↗

[Imiquimod, pegylated interferon-alpha-2b and interleukin-2 in the treatment of cutaneous melanoma metastases].

The immune system plays an important role in the defense against malignant melanoma. Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) are therapeutically used for unspecific stimulation of the immune system. After intralesional injections of these cytokines into cutaneous melanoma metastases, regression has been observed. In view of its immunomodulating effects, imiquimod appears as an additional promising therapeutic option for treatment of malignant tumors. In a case report, we present combined therapy with intralesional IL-2, pegylated IFN-alpha-2b and topical imiquimod 5% cream for disseminated cutaneous metastatic malignant melanoma stage IIIa. This therapy achieved an almost complete remission. In a treatment period of eight months, side effects remained tolerable. Histologically, both fibrosis and inflammation were found in the regressing lesions. After the end of therapy, no disease progression occurred during 11 months follow-up.

Adjuvants, Immunologic↗

Maintenance of the placental circulation to evaluate and treat an infant with massive head and neck hemangioma.

A maternal ultrasound was obtained because of polyhydramnios at approximately 30 weeks gestation. The study identified a fetus with a large, solid mass involving the neck and left face. Because of the concern for airway obstruction, we sought an alternative to normal delivery or routine cesarean section. At 35.5 weeks gestation the mother underwent deep halothane anesthesia followed by cesarean section. Initially, only the head and neck of the fetus were delivered and a large hemangioma was noted to involve the anterior and left neck and all of the left face to the left eye. While maintaining placental and umbilical cord circulation, the infant was successfully nasotracheally intubated. The umbilical cord was divided and the delivery completed. At 1 week of age the infant underwent partial excision of that portion of the hemangioma overlying the trachea and the left external carotid artery was ligated. The infant was successfully extubated 12 days later. In the first 4 months of life she had three episodes of platelet trapping requiring high-dose systemic steroid therapy. Beginning at 8 months of age she was begun on intralesional injections of a 50/50 solution of triamcinolone and betamethasone with a marked reduction in the size of the lesion. Preservation of the placental circulation during delivery resulted in the avoidance of a potential hypoxic or fatal event. Intermittent intralesional steroid injections appear to have played a role in the marked reduction in the size of this large subcutaneous head and neck hemangioma.

Adult↗

A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts.

To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted.

Administration, Topical↗

Wrist and hand ganglion treatment with hyaluronidase injection and fine needle aspiration: a tropical African perspective.

In an attempt to provide an alternative non-invasive treatment to surgical excision of ganglion cysts of the hand, and as part of the departmental audit resulting from the prevailing economic depression, 340 consecutive patients with 349 ganglia were treated in a prospective investigation by intralesional injection of hyaluronidase (up to 150 units in 1 ml) followed by fine needle aspiration (FNA) of the cyst to dryness. Pressure was applied over a piece of gauze and maintained with a crepe bandage for 24 h. Of the 340 patients treated in this way, the vast majority (323 or 95.0%) were considered to be cured on clinical examination at 6-month follow-up; only 17 patients (5.0%) exhibited recurrence during this period and these were successfully treated by re-aspiration. To the knowledge of this author, this is the first report of the use of the enzyme hyaluronidase as an adjunct to FNA in the treatment of ganglion cysts of the hand. The results clearly show that this method of treatment is a safe, fast, well accepted and cost-effective alternative to surgical excision, which is relatively expensive and is known to be associated with certain complications, including hypertrophic scars and cheloids.

Adolescent↗

Phase 2 trial of Allovectin-7 in advanced metastatic melanoma.

Treatment of metastatic melanoma with chemotherapeutic regimens has led to disappointing response rates, duration of response and no appreciable impact on survival. Intralesional injection of a low dose of an HLA-B7/beta2 microglobulin plasmid formulated with cationic lipids (Allovectin-7 is a registered trademark of Vical, Incorporated, San Diego, California, USA) has been shown previously to be safe and well tolerated. A phase 2, open-label study was performed at 16 centers in the United States. Seventy-seven patients were treated with 10 mug intralesional Allovectin-7 weekly for 6 weeks and clinical response to treatment were evaluated by World Health Organization criteria. Minimal adverse events were associated with the Allovectin-7 injections. Seven patients (9.1%) had complete or partial response with 4.8 months median duration of response. Allovectin-7 was shown to be safe and exhibit biological activity at this dose. Its safety profile may enable Allovectin-7 to be used at higher doses, which may provide greater clinical activity.

Adult↗

Oral and intralesional steroid therapy in giant cell granuloma.

Giant cell granulomas account for 7% of all benign tumors of the jaw. They are commonly seen as asymptomatic masses. A 4-year-old boy with an exophitic, crusty, hemorrhagic mass on the anterolateral region of the right maxilla was referred to our department. Pathological examination was reported as giant cell granuloma. A mixture of prednisolone, lidocaine and adrenaline was injected intralesionally once a week and oral fluocortone was added to this therapy. A limited surgery could be performed. Intralesional prednisolone and systemic fluocortone therapy seems to be effective, as the lesion stopped growing and increase in bony structures was observed radiologically.

Administration, Oral↗

Treatment of scalp angiosarcoma by controlled perfusion of A. carotis externa with pegylated liposomal doxorubicin and intralesional application of pegylated interferon alfa.

BACKGROUND: Angiosarcoma of the scalp is a rare but highly aggressive malignant tumor that differentiates toward vascular endothelial cells and shows a tendency for diffuse, often clinically occult spread. OBSERVATIONS: A 65-year-old Caucasian man presented with multiple erythematous skin lesions at the right scalp hemisphere and a prominent forehead edema that had developed during a period of 2 months. The clinical diagnosis of angiosarcoma was confirmed by histopathology. Because of the advanced local progression of the tumor and the unilateral localization on the right side of the scalp, we initiated an intra-arterial chemotherapy using pegylated liposomal doxorubicin (Caelyx) (8 mg/cycle every 4 weeks by an A. carotis externa port system). In addition, the patient received pegylated interferon alfa (50 microg/wk) by a percutaneous intralesional injection route. After 2 months, the tumor showed a marked regression; after 4 months, only one nodule located at the margins of the area perfused by the A. carotis externa persisted but regressed after focal irradiation. At 30 months after diagnosis, the patient shows no recurrence of tumor growth. CONCLUSIONS: In combination with intralesional interferon alfa, intra-arterial doxorubicin may be a promising innovative therapeutic option for localized scalp angiosarcoma, a hitherto poorly manageable and aggressive malignant tumor.

Aged↗

Inhibition of tumor growth by the intralesional administration of interleukin-3 into mice implanted with solid tumors.

The antitumor activity of three interleukin-3 (IL-3) preparations administered intralesionally into mice bearing syngeneic solid tumors was investigated. IL-3 preparations used in this study included S-IL-3, which was isolated from the culture fluid of murine inguinal lymph node cells stimulated with an arabinomannan extracted from Mycobacterium tuberculosis (SSM), the culture fluid of WEHI-3 cells (W-IL-3) and recombinant IL-3 (rIL-3). When a 1,500 U/kg dose of S-IL-3 or W-IL-3 was injected intralesionally into BALB/c mice bearing Meth-A solid tumors three time per week beginning 3 days after tumor inoculation, tumor growth was inhibited by 60% or 74% at 24 days after tumor inoculation, respectively. In these experiments, 1 unit of IL-3 activity was determined to be the concentration that induced 50% of maximal proliferation of an IL-3 dependent cell line (FCD-P2 cells). The administration of this dose of rIL-3 inhibited tumor growth by 34%. When these three preparations of IL-3 were pretreated with anti-IL-3 monoclonal antibody in vitro, the antitumor activity, as well as their growth promoting activity on FDC-P2 cells, was eliminated. Since direct cytotoxic activities of these IL-3 preparations against cultured Meth-A tumor cells in vitro have not been demonstrated, these results suggest that their antitumor activities might be expressed through interactions between tumor cells and antitumor effector cells which were stimulated by the intralesional administration of the IL-3 preparations.

Animals↗

Treatment of aggressive basal cell carcinoma with intralesional interferon: evaluation of efficacy by Mohs surgery.

BACKGROUND: Intralesional interferon has shown activity in the treatment of noduloulcerative and superficial basal cell carcinomas (BCC). OBJECTIVE: Our purpose was to study the efficacy of intralesional interferon in the treatment of aggressive BCCs. METHODS: Fifteen patients with histologically proven primary morpheaform or recurrent BCCs were referred for Mohs surgery. They received nine intralesional injections of 1.5 million IU of interferon alfa-2b three times a week for 3 weeks (total dose 13.5 million IU). All tumors were located on the face and measured 7 to 25 mm in diameter. RESULTS: In four patients (27%) no residual tumor was found at surgery. In five (33%) tumor size was reduced by 75%. The remaining six patients (40%) showed no response to intralesional interferon. CONCLUSION: At the dosage used, interferon was able to cure only a minority of aggressive BCCs.

Aged↗

Intralesional recombinant interferon alpha-2b in Peyronie's disease.

OBJECTIVE: To evaluate interferon alpha-2b (IFN) in the treatment of Peyronie's disease (PD) since IFN exerts antifibrotic action through collagen synthesis inhibition and fibrolysis stimulation. METHODS: The study comprised 34 patients, aged 31 to 63, with clinical and ultrasonographic (US) diagnosis of PD, who gave their consent to enter the study. They had the disease for 10.1 +/- 5.6 (2-22) months. Ten million IU of IFN were injected intralesionally, twice weekly for 14 weeks or less if there was complete remission. Clinical evaluation included penis angle at erection, sexual dysfunction (pain, possibility of intercourse) and palpable plaque. Plaque size was evaluated by US. Systemic and local adverse reactions, and anti-IFN antibodies were monitored as well. RESULTS: Sexual dysfunction disappeared in 19/24 (79.2%) patients with this disorder, palpable lesions in 21/34 (62%), angle at erection in 15/32 (47%), and pain in 16/17 (94%). Complete clinical response was achieved in 16/34 patients (47%). Ultrasonographic response rate was 88%, (53% complete). Plaque size decreased from 56.7 +/- 42.9 (median: 35.4) before treatment to 12.7 +/- 22.6 mm2 (median: 0) (p < 0.00001; Wilcoxon's paired test). Clinical and US responses correlated. No patient showed progression. Eight of 9 patients in whom other treatments had failed responded to IFN therapy (5 complete). The main systemic adverse reaction in most patients (mild or moderate) was the flu-like syndrome expected for IFN. Local reactions, more related to the administration procedure than to IFN itself, were small hematoma (10 patients), edema (3), cysts that were excised surgically (2), and venous leak (1). No patient developed anti-IFN antibodies. CONCLUSIONS: IFN treatment can be a suitable option for the management of PD. The results appear to be better than those achieved with other procedures. Further work should include comparative studies, long-term follow-up of treated patients, and alternative ways of administration.

Adult↗

Tumor-infiltrating macrophages are involved in suppressing growth and metastasis of human prostate cancer cells by INF-beta gene therapy in nude mice.

PURPOSE: This study was to determine the role of tumor-infiltrating macrophages in IFN-beta-induced host defense against prostate cancer. EXPERIMENTAL DESIGN: Efficacy of adenovirus-mediated IFN-beta gene therapy against orthotopic xenografts of human prostate cancer was tested in macrophage-compromised nude mice. Immunohistochemistry and Northern blotting were used to elucidate mechanisms responsible for the IFN-beta gene therapy. RESULTS: PC-3MM2 human prostate cancer cells were inoculated into the prostates of nude mice. Intralesional injection of an adenoviral vector-encoding murine IFN-beta (AdmIFN-beta) but not control vector AdE/1 suppressed growth of PC-3MM2 tumors in a dose-dependent manner, with a maximal reduction of tumor weight by approximately 85% at 2 x 10(9) plaque-forming units. The therapy prevented metastasis, eradicated established metastases in some mice, and prolonged the survival of tumor-bearing mice. The efficacy of AdmIFN-beta therapy was reduced significantly in mice treated with macrophage-selective anti-Mac-1 and anti-Mac-2 antibodies. Moreover, the i.p. injection of the antibodies restored the tumorigenicity of PC-3MM2 cells stably engineered with murine IFN-beta gene. Tumor-infiltrating macrophages, significantly increased in AdmIFN-beta-injected lesions, were depleted by the antibodies. The therapy stimulated expression of the inducible nitric oxide synthase, down-regulated transforming growth factor-beta1 and interleukin-8, reduced microvessel density, and resulted in apoptosis of endothelial cells in the lesions. These effects of AdmIFN-beta were partially diminished in mice treated with the antibodies. CONCLUSIONS: These data suggest that macrophages play an important role in IFN-beta gene therapy and that intralesional delivery of the IFN-beta gene could be an effective therapy for clinically localized human prostate cancer.

Adenoviridae↗