[Treatment of cheloids and cheloid scars with intralesional corticoid injections].
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Tumor-infiltrating lymphocytes (TIL) and regional lymph node lymphocytes (LNL) were isolated by mechanical disaggregation and density gradient centrifugation from 30 untreated human lung tumors and 12 BCG-injected human lung tumors. Lymphocyte populations were characterized by their ability to form erythrocyte (E)-rosettes, erythrocyte-antibody-complement, and erythrocyte-antibody gamma-rosettes, by their proportion of esterase-staining cells, and by their responses in mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML). and natural killer (NK) assays. TIL from untreated tumors had low proportions of E-rosetting cells (mean, 27.3%), relatively high proportions of "null" cells, and poor responses in MLC-CML and NK assays. There were no significant differences between primary lung tumors and lung metastases in rosettes, MLC-CML responses, or NK activity. In contrast, TIL from tumors injected with BCG 14 days before resection had higher proportions of E-rosetting cells (47.8%) and vigorous MLC-CML and NK responses. LNL from 11 patients with untreated tumors had higher proportions of E-rosetting cells (40.5%) than LNL from 9 patients with BCG-injected tumors (35.0%) and LNL from patients with untreated tumors had higher responses than LNL from treated patients in MLC-CML assays. These results suggest that the BCG injection induced an infiltration of functionally reactive NK and T-cells at the tumor site without an associated increased activity of T-cells from regional lymph nodes.
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BACKGROUND: Rituximab is a genetically engineered antibody directed against the CD20 antigen. Intravenous administration of rituximab has been used for the treatment of patients with low-, intermediate-, and high-grade B-cell non-Hodgkin's lymphomas and is a registered treatment modality for this indication. Treatment of primary cutaneous B-cell lymphoma (CBCL) with intralesionally or systemically administered rituximab has been described only in a few cases. OBJECTIVE: Our purpose was to assess the efficacy of rituximab in the treatment of CBCL. METHODS: We performed a retrospective study on 9 patients with CBCL who were treated with intralesional or systemic administration of rituximab. RESULTS: Two patients treated with systemic rituximab achieved complete remission. Complete remission could be observed in 6 of 7 patients after 1 to 8 cycles of intralesional treatment with rituximab. In one patient one of two lesions showed a partial remission after 4 cycles of treatment, whereas the second showed complete remission. A local recurrence was observed in one patient after 27 months of follow-up and in two patients recurrences developed at other body sites after 12 and 14 months of follow-up. No severe side effect occurred except for slight pain during intralesional injection. CONCLUSION: Rituximab therapy is a well-tolerated and effective treatment for primary CBCL. In comparison to intravenous administration, intralesional application of the drug allows the use of lower dosages. Intralesional therapy with rituximab deserves further investigation and comparison to systemic administration of the drug in controlled multicenter studies.
Benign lymphangiomas are encountered frequently in the head and neck region. They may be well circumscribed or diffusely invasive, involving subcutaneous tissue and underlying muscle, and consist of dilated, thin-wall sinuses. Surgical therapy with excision as wide as possible, while taking care to avoid rupturing the lesion, is the treatment of choice. To simplify complete excision, the authors introduce an intraoperative technique--intralesional injection of fibrin glue. Using this technique over period of 10 years in 27 patients (age range, 7-24 years) they removed successfully intra- and extraoral lymphangiomas. There have been no recurrences. This technique helps avoid rupture of the epithelium and bleeding, and makes it easier to remove lymphangiomas surgically and as completely as possible. This technique reduces recurrence remarkably and ensures successful surgical excision.
STUDY DESIGN: The clinical records and radiographs of 18 patients with vertebral hemangiomas treated with ethanol vertebroplasty were reviewed to evaluate the usefulness of this method. OBJECTIVES: To assess, after a mean 2-year follow-up, the complication rate, results, and patient satisfaction with ethanol injection into vertebral hemangioma. SUMMARY OF BACKGROUND DATA: There is controversy about the safety of ethanol injections in the treatment of vertebral hemangiomas. METHODS: Twenty-four patients with vertebral hemangiomas were prepared for ethanol vertebroplasty. Eighteen patients were treated with ethanol vertebroplasty (average age, 49 years; range, 18-77 years) with a mean follow-up of 2 years (range, 1-4 years). The rest of the patients were not treated with ethanol vertebroplasty because in a pretreatment test injection the contrast medium was not retained by the hemangioma. RESULTS: Intralesional injections of alcohol did not cause clinical complications in any of the cases. CONCLUSIONS: This study shows that intralesional alcohol injections can be considered a safe technique for vertebral hemangiomas. However, a careful technique is required.
Intralesional corticosteroids have been used in the treatment of hypertrophic keloid scars for over 40 years. The few complications documented have mostly been local skin changes, viz depigmentation and cutaneous atrophy. Cushing's syndrome following intralesional injection is rare and usually self-limiting following cessation of therapy. This report describes a 9-year-old girl who developed Cushing's syndrome 2-3 weeks after a single treatment with 40 mg triamcinolone acetonide injected into keloids. Features of Cushing's syndrome and a suppressed hypothalamic-pituitary axis were present up to 9 months later. Three years after glucocorticoid injections, features of Cushing's syndrome had largely disappeared. Dosages of intralesional steroids normally recommended for adults are inappropriate for children.
AIM AND BACKGROUND: Recent data in the literature indicate that antigen-presenting cells (APC) are inactive in tumour tissue because of local immunosuppression. Tumour-infiltrating lymphocyte (TIL) signal activation transducing mechanisms are also seriously impaired. Administration of granulocyte macrophage-colony stimulating factor (GM-CSF) may lead to APC recovery and interleukin (IL)-2 may restore local TIL activation. Moreover, IL-2 increases the systemic lymphocyte population, an event that seems to correlate with a better prognosis. STUDY DESIGN: The present phase I-II study was carried out to examine whether intralesional injection of GM-CSF followed by subcutaneous IL-2 would induce a clinical response in advanced, pretreated elderly melanoma patients. METHODS: Sixteen patients over 60 years of age received intralesional GM-CSF (150 ng per lesion on day 1), generally divided between the two largest cutaneous lesions, followed by perilesional subcutaneous IL-2 (3,000,000 IU) for 5 days (days 3-7 inclusive) every 3 weeks. RESULTS: Four clinical responses [two partial (PR) and two minimal (MR)] (25%), which also involved lesions that had not been directly treated, and nine cases of stable disease were observed. The response duration for PR and MR was 9, 4, 4 and 2.5 + months, respectively. Stable disease (56%) recorded in the nine patients was short-term (3-6 months). Three patients rapidly progressed after two, two and one therapy cycles, respectively. The patient who reached the best PR had a fairly high absolute lymphocyte count (1600-2400/mm3). The second one, who reached complete remission after subsequent locoregional chemotherapy and hyperthermia, however, had a low absolute lymphocyte count that had doubled 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.
Hydrogen peroxide (H2O2) and superoxide anion (O2-) were estimated in lesional cells from 10 lepromatous leprosy patients injected intralesionally with recombinant interferon-gamma (rIFN-gamma). Clinically similar contralateral lesions injected with excipient served as controls. Lesional esterase-positive cells (suggestive of monocytes/macrophages) from rIFN-gamma-injected sites of many subjects showed net increments in the H2O2 and O2 levels compared to controls. When these cells were exposed to Mycobacterium leprae in vitro, there was a down-regulation of O2- in 4 of 5 subjects. Such inhibition was not observed in rIFN-gamma-injected sites. From the present studies it was not possible to determine whether the above effects of rIFN-gamma were primarily on lesional mature macrophages or on newly migrated young monocytes. Erythema and induration were observed at the cytokine-injected site but not at the control site between 24 and 72 hr. A monthly slit-skin smear examination of the former site showed a bacterial index (BI) reduction compared to the controls in 4 of 10 patients, this reduction occurring as early as 4 to 8 weeks. Histopathology of the biopsies of 6 of 10 subjects between 9 and 10 months showed a further BI decrease attributable to rIFN-gamma and not to the subsequently instituted chemotherapy.
BACKGROUND: OncoGel (ReGel/paclitaxel) is an intralesional injectable formulation of the chemotherapeutic drug, paclitaxel, for local tumor management. OBJECTIVE: The aim of this study was to determine if a minimally invasive EUS-guided injection of paclitaxel, bound to a thermosensitive gel carrier, would lead to therapeutic tissue concentrations of the chemotherapeutic agent in the porcine pancreas. DESIGN: Eight Yorkshire breed pigs were sedated by general anesthesia and OncoGel was injected, under EUS-guidance, with a 22-gauge needle into the tail of the pancreas. MAIN OUTCOME MEASUREMENTS: During the 7-day (n = 4) or 14-day (n = 4) observational period, the animals were monitored by serum levels of amylase and lipase, and by a CT on day 4. The outcome was determined by gross and microscopic evidence of inflammation of the pancreas, clinical tolerance, and quantitation of tissue paclitaxel concentrations. RESULTS: Eight pigs underwent injection of 1, 2, 3, or 4 mL OncoGel (6 mg paclitaxel per 1 mL OncoGel) (n = 2 per group). An intrapancreatic hyperechoic focus, with an average diameter of 2.1 +/- 0.8 cm, was visible by EUS, and a hypodense area in the tail of the pancreas was visible by contrast CT. Clinically, the animals appeared to tolerate the procedure without sequelae. Blood levels of amylase and lipase were normal. At euthanasia, a depot of OncoGel, with an average diameter of 14.7 +/- 5.0 mm), was located both grossly and histologically in the pancreatic tail. After 14 days, clinically significant tissue concentrations of paclitaxel were detected at a distance of 30 to 50 mm from the depot in the animals that underwent an injection of 3 and 4 mL of the agent (n = 2). CONCLUSIONS: The EUS-guided injection of OncoGel into the pancreas of the pig provided high and sustained localized concentrations of paclitaxel. This technique is a potential minimally invasive local treatment option for unresectable pancreatic tumors.
Ten strains of anaerobic Corynebacteria were compared in their effect on survival of C57BL/6 mice, bearing subcutaneously inoculated B16 melanomas. The corynebacterial suspensions were injected intralesionally twice weekly for five injections. Significant permanent tumor regression was not obtained. Significant prolongation of survival was observed in mice treated with seven of the corynebacterial strains.
DermaLive is a long-term wrinkle reduction product including two types of components: pure hyaluronic acid, produced in cell culture, and an acrylic hydrogel. The product was first marketed in France and the rest of Europe in 1998. We have over three years of experience with this product. Several studies have been conducted simultaneously, mainly in Germany and in France. At present, DermaLive is used in the long-term correction of natural or acquired skin depressions (caused by aging, trauma) or the creation of volume (lips, sunken cheekbones). It provides a worthwhile alternative to good-quality bioresorbable materials (pure hyaluronic acid or collagen)--materials that are so resorbable, in fact, that most patients are ultimately dissatisfied with the results--and to other so-called permanent materials that patients do not tolerate well. Filling involving the use of autologous fat transplantations, which yields satisfactory results, is not appropriate for ambulatory injection and, therefore, will not be examined in detail. The tolerance experienced with DermaLive three years on is, at present, considered highly satisfactory. The wrinkle reduction effect obtained after the first injection is long-lasting with 60% resorption of the initial material. Two or three injections, with an interval of at least three months between each, may be required to bring about the reduction of some wrinkles or the correction of post-scar depressions. Side effects occurring long after the injection are rare (1.2 for 1,000). They appear mainly as palpable nodules occurring about six months after injection. They are treated by intralesional injection of corticoids. DermaLive and DermaDeep are both filler implants with a long-lasting effect designed for corrective and aesthetic surgery. Instruction of use and intervals between injection sessions must be respected. After DermaLive or DermaDeep injection, injections of pure hyaluronic acid (Juvederm or Restylane) for treatment of fine lines and superficial defects yield safe and excellent aesthetic results.
OBJECTIVES: A prospective study was performed to assess the intermediate and long-term efficacy of intralesional cidofovir therapy associated with surgical excision in laryngeal papillomatosis in adults. METHODS: Endoscopy with intralesional injection of cidofovir 5 mg/mL was performed 3 times at 4-week intervals. The concentration was later increased to 7.5 mg/mL and the interval between injections shortened to 2 weeks. Further treatment was performed at 3 or 6 months, depending on the evolution of the papillomas. After complete remission, the treatment was stopped and the patients were reviewed every 6 months. RESULTS: Nineteen patients completed the protocol, with a mean of 4.5 injections each. Complete remission was obtained in 17 cases (89%) after a mean of 3.8 procedures. Remission was stable after a mean follow-up of 24 months (range, 8 to 57 months). With higher cidofovir concentrations at shorter intervals, patients needed fewer injections to achieve remission (mean, 2.1 versus 4.7 injections). CONCLUSIONS: The effectiveness of intralesional cidofovir therapy in adult-onset recurrent respiratory papillomatosis was impressive. Once obtained, complete remission was stable on intermediate or long-term follow-up. The concentration and the interval between injections seemed to influence the number of injections necessary to achieve remission.
We reviewed 32 children after the treatment of simple bone cysts by intralesional injections of methylprednisolone acetate. The age of the child and the activity and size of the cyst did not significantly affect the radiological outcome. The earliest time at which the radiological response could be reliably determined was three months. After a median period of review of five years, four (13%) cysts had healed, 20 (62%) cysts were partially visible but sclerotic, four (12.5%) were still visible but opaque and four (12.5%) were clearly visible. The healed and partially visible but sclerotic cysts were classified as having satisfactory radiological healing. This was observed in 13 of 32 cysts (41%) after the first injection, in eight of 21 (38%) after the second injection, but in relatively few of the remaining cysts after subsequent injections. A satisfactory symptomatic outcome was achieved in all of the 18 children with humeral cysts and in the one child with a fibular cyst irrespective of the radiological outcome, but only in nine (67%) of the 13 children with femoral or tibial lesions, in whom the cysts were healed or sclerotic. The remaining four children had exertional bone pain and repeated fractures of their femoral or tibial cysts which were incompletely healed with sclerosis in one and opacities in three. We conclude that the healing response to intralesional corticosteroids is unpredictable and usually incomplete even after multiple injections. The failure rate in weight-bearing bones is too high.
The therapeutic potential of locally injected interleukin-2 (IL-2) or interleukin-4 (IL-4) was studied in the footpads of Leishmania mexicana or Leishmania major infected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL-2 (0.5 microgram/dose) or IL-4 (0.1 microgram/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on which Leishmania species was used and at what time during the course of disease that therapy commenced. Both L. major and L. mexicana infections, as measured by footpad thickness and parasite number, were exacerbated if IL-4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e. after measurable lesions had developed) of IL-4 markedly inhibited both lesion size and parasite growth in L. major, though not L. mexicana, infected mice. IL-2 had no measurable effect on the course of L. major infections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL-2 did exacerbate L. mexicana lesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increases in parasite number.