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PubMed1999

Pressure measurements during injection of corticosteroids: in vivo studies.

Intralesional injection of corticosteroids is an effective treatment for capillary hemangiomas. Complications include embolisation of corticosteroid particles into the ocular circulation resulting in permanent loss of vision. This research is aimed at developing an injection cannula and monitoring system to prevent such inadvertent embolisation. A cannula has been designed to simultaneously estimate the pressure at its tip and the flow rate during injection. The estimation technique has previously been validated using an in vitro model. In this study, the cannula was tested in vivo with canine liver at injection flow rates of 2.5 to 21 ml min-1. The pressure generated in the tissue during injection was calculated using the technique developed. This was compared with direct in situ pressure measurements made with a coaxial outer cannula. The mean calculated pressure was seen to be linearly related to the mean measured pressure with a slope of 0.97, correlation coefficient of 0.99 and standard error of 2.74 mmHg. Similar trends were observed between the maximum calculated and maximum measured injection pressure: slope = 1.0, r = 0.99 and standard error = 5.54 mmHg. The estimation of the mean and maximum pressure from the cannula and monitoring system was accurate in canine liver. High pressures close to 250 mmHg were generated in tissues during injection.

Animals↗
PubMed1997

Phase I study of direct gene transfer of an allogeneic histocompatibility antigen, HLA-B7, in patients with metastatic melanoma.

PURPOSE: To determine the safety, toxicity, and efficacy of direct intratumoral injection of an allogeneic major histocompatibility complex (MHC) class I gene, HLA-B7, in a cationic lipid vector (Allovectin-7; Vical Inc, San Diego, CA) in patients with metastatic melanoma. PATIENTS AND METHODS: Seventeen HLA-B7-negative patients were treated with intralesional injection of Allovectin-7. Twelve patients received a single intralesional injection containing 10 micrograms (four patients), 50 micrograms (five patients), or 250 micrograms (three patients) of plasmid DNA. Five patients received two or three injections of 10 micrograms DNA to a single tumor site at 2-week intervals. Tumor biopsies pretherapy and 2 and 4 weeks after gene injection were obtained to determine expression of the plasmid by polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, flow cytometry, and immunohistochemistry. RESULTS: Toxicities were related to technical aspects of the injections or biopsies. These included pain, hemorrhage, pneumothorax, and hypotension. Two patients were hospitalized overnight for observation. Seven patients (50%) had tumor responses insofar as the injected nodule decreased > or = 25% by radiologic or physical examination. One patient with a single site of disease achieved a complete remission. Ninety-three percent of the patients' post-gene therapy biopsies contained HLA-B7 plasmid DNA, mRNA, or protein. CONCLUSION: Intratumoral injection of the allogeneic histocompatibility gene, HLA-B7, in a lipid vector can be performed safely at plasmid DNA doses < or = 250 micrograms. The safety profile and biologic activity of this therapy warrants further studies to define the mechanism of action, predictors of response, and antitumor efficacy of this approach.

Adult↗
PubMed1995

Immunotherapy of a plasmacytoma with attenuated salmonella.

An attenuated strain of Salmonella typhimurium, SL3235, developed as a prototypic typhoid vaccine, is shown to retard growth of a murine plasmacytoma, TEPC-183, and to prolong survival of tumor-bearing mice. Live salmonella, but not acetone-killed organisms, had antitumor activity. The immunotherapeutic effect was demonstrable when the tumor was injected intralesionally or intraperitoneally. Increased survival, longer mean time to death, and retardation of tumor growth were found when the salmonella were given intralesionally as late as the sixth day post-tumor injection. Timing of salmonella inoculation, as well as the salmonella dose, had an effect on treatment efficacy. Injection of salmonella intraperitoneally exerted a strong antitumor effect when given as late as the third day post-tumor inoculation. The highest dose (2 x 10(6)) of salmonella was less effective than doses 10- or 100-fold lower. TEPC-183 plasmacytoma is rapidly growing and highly immunosuppressive, so the ability of the salmonella to exert therapeutic activity against it is a measure of the potency of the vaccine. These observations are of interest, as they show that a genetically engineered, avirulent strain of Salmonella has immunotherapeutic properties similar to those of BCG and other biological response modifiers, and might have clinical potential as an antitumor agent.

Animals↗
PubMed2005

Intralesional 5-fluorouracil in the treatment of keloids: an open clinical and histopathologic study.

BACKGROUND: The treatment of keloids remains unsatisfactory. Intralesional 5-fluorouracil (FU) has not been much investigated as a monotherapy in the treatment of keloids. OBJECTIVE: We sought to evaluate the use of intralesional injections of 5-FU in the treatment of keloids. METHODS: A total of 20 patients (11 male and 9 female) were treated once weekly with intralesional injections of 5-FU (50 mg/mL). Patients received an average of 7 treatments. Average injection volumes were 0.2 to 0.4 mL/cm2. All patients had full blood cell count, liver function tests, and renal function tests before and after treatment was commenced. A total of 10 patients had biopsy specimens taken before starting treatment as a baseline and after 6 sessions. Routine hematoxylin-eosin and immunohistochemical analysis detecting Ki-67 and transforming growth factor-beta were performed on paraffin sections. All patients were followed up for 12 months, or until recurrence was noted. RESULTS: Of 20 patients, 17 (85%) showed more than 50% improvement. Only one did not respond favorably. Small and previously untreated lesions improved the most. Pain (20 of 20), hyperpigmentation (20 of 20), and tissue sloughing (6 of 20) were the main adverse effects. Histopathologic and immunohistochemical evaluation were consistent with the clinical observations. Ki-67 proliferative index was significantly reduced (P = .0001) after treatment. Transforming growth factor-beta was reduced less significantly. Recurrence was noted in 47% (9 of 19) of patients who responded to treatment within 1 year. A correlation was found ( P = .028) between the duration of the lesions and recurrence. CONCLUSION: Our study demonstrates that intralesional 5-FU may be effective in the treatment of keloids, but recurrence is common and further investigation is required.

Adolescent↗
PubMed2000

A review of topical and intralesional cidofovir.

Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency Syndrome (AIDS). It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or by intralesional injection in several virally induced cutaneous diseases. Available information demonstrates that cidofovir is a potent antiviral agent with activity against several DNA viruses that cause cutaneous disease when applied topically or administered by intralesional injection. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in animals and a limited number of patients including those infected with human immunodeficiency virus (HIV). This article reviews the pharmacology of cidofovir and the utility of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir resistant strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and monkeypox.

Administration, Topical↗
PubMed1996

Successful treatment with fluconazole of protothecosis developing at the site of an intralesional corticosteroid injection.

We report a case of cutaneous protothecosis treated successfully with oral fluconazole. Fluconazole appears to be an effective alternative to conventional drugs for the treatment of cutaneous protothecosis. Cutaneous protothecosis is an uncommon infection due to achlorophyllic, saprophytic, algae-like unicellular organisms of the genus Prototheca that occurs mainly in immunocompromised patients. To date there is no standard treatment regimen. Surgical excision, oral ketoconazole, intravenous amphotericin B alone or in combination with oral tetracycline have been reported to be effective in the management of protothecosis. We report a 55-year-old immunocompetent woman with cutaneous protothecosis which developed at the site of intralesional triamcinolone acetonide injection, who was successfully treated with oral fluconazole.

Antifungal Agents↗
PubMed1977

Granulomatous hepatitis in a healthy adult following BCG injection into a plantar wart.

This is the first reported case of granulomatous hepatitis in a healthy adult following intralesional injection of BCG into a plantar wart. Previous reports of disseminated disease following intralesional injections have all been in patients with malignancies. The clinical course in this patient was characterized by fever, chills and drainage from the injection site. Diagnosis was made by demonstration of noncaseating granulomas on liver biopsy. No acid-fast organisms were identified by stain or culture. The patient responded to antituberculous therapy.

Adult↗
PubMed1998

The vascular space-like structure in melanocytic nevus is not an injection artifact: report of a case and an experimental study.

Melanocytic nevi may microscopically associate with clefts or slits of the nests resembling lymphatic or vascular spaces. This unique histologic feature has been known as an artifact of injection or tissue-processing. We present a case of melanocytic nevus with a prominent vascular space-like structure. We also studied whether intralesional injection of local anesthetic could reproduce similar histologic findings. A 45-year-old Japanese female visited us with a solitary, brownish papule on the chest. Histology revealed numerous nests composed of round to oval-shaped nevus cells throughout the entire dermis. In the mid-dermis, nevus cells were lined up in a layer anastomosing and forming a vascular space-like structure. These nevus cells were uniformly stained with vimentin and S100 protein but not with factor VIII-related antigen. They were also positively immunoreactive with anti-type IV collagen and anti-fibronectin. There were no significant differences in staining intensity in the nevus cells between the solid portion and the vascular space-like structure. In the experimental study, eight melanocytic nevi were removed under local anesthesia. The local anesthetic solution was then injected into the excised nevus. Intralesional injection of a considerable volume of local anesthetic was capable of causing slits or clefts of the nests and dermal edema; however, it failed to reproduce a vascular space-like structure similar to that in the present case. These findings suggest that a vascular space-like structure in melanocytic nevus is not caused by the injection alone. Some other factor(s) may play a major role in the development of such structures in melanocytic nevus.

Adolescent↗
PubMed2002

Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids.

BACKGROUND: The treatment of keloids remains challenging. Cryosurgery and intralesional corticosteroids have been considered as the mainstream of therapy; however, the long-term use of corticosteroids has been found to be associated with serious side effects. Intralesional 5-fluorouracil (5-FU) has only been used in one study for the treatment of hypertrophic scars and keloids, mostly in combination with other treatments. The efficacy of 5-FU as an individual therapeutic agent is unknown. OBJECTIVE: To evaluate the efficacy and safety of intralesional injections of 5-FU in the treatment of small keloid lesions. METHODS: Twenty-four (12 male, 12 female) consecutive patients with keloids of 6 cm or less in their maximum dimension were treated with intralesional injections of 50-150 mg 5-FU per week for a maximum of 16 injections. RESULTS: One third (8/24, 33.3%) of the patients showed more than 75% flattening of the keloid. Three out of 8 patients (with >75% flattening) required less than 16 (13, 13 and 15) injections for achieving the desired response. Overall, about half of the patients showed more than 50% flattening of the treated keloid. A correlation with the duration of keloid was found. Six (54.5%) out of 11 patients with keloids of < or =5 years duration, in contrast to only 2 (15.4%) out of 13 patients with keloids of >5 years duration showed more than 75% flattening (p < 0.05). Side effects included pain (all patients), hyperpigmentation (all patients) and ulceration (1 patient). No difference in peripheral blood count was noted before, during and after the therapy. CONCLUSION: Intralesional 5-FU can be safely used for the management of small keloids of shorter duration.

Female↗
PubMed1988

Intralesional therapy of cutaneous leishmaniasis with sodium stibogluconate antimony.

One hundred and thirty lesions of cutaneous leishmaniasis in 60 patients were treated with intralesional injections of Pentostam and 30 lesions were left untreated as controls. The injections were given at 8-day intervals and the patients followed-up for 42 days. One hundred and four lesions (80%) needed one injection only, 20 (15.4%) needed two and six (4.6%) needed three injections. One hundred and twenty three of the treated lesions (94.6%) showed a good clinical response with complete healing or marked improvement within the follow-up period. None of the control lesions showed marked improvement or complete healing. Scarring was minimal or absent following healing of treated lesions. The only side-effect was some localized pain following the injection. We recommend intralesional Pentostam as a safe and effective method of treating acute cutaneous leishmaniasis.

Acute Disease↗
PubMed2004

Intratumoral injection of cyanoacrylate glue in head and neck paragangliomas.

BACKGROUND AND PURPOSE: Substantial intraoperative bleeding during surgical removal of head and neck paragangliomas may be a major problem in the management of these highly vascularized tumors. Traditional preoperative embolization via a transarterial approach has proved beneficial but is often limited by complex vascular anatomy and unfavorable locations. We report our experience with the preoperative devascularization of head and neck paragangliomas by using direct puncture and an intralesional injection of cyanoacrylate. METHODS: We retrospectively analyzed nine consecutive patients with head and neck paragangliomas who were referred for preoperative devascularization. Three patients were treated for carotid-body tumors; two for vagal lesions; and four, for jugular paragangliomas. Direct puncture of the lesion was performed by using roadmap fluoroscopic guidance. Acrylic glue was injected by using continuous biplane fluoroscopy. All patients underwent postembolization control angiography and immediate postoperative CT scanning. RESULTS: Angiograms showed that complete devascularization was achieved in all cervical glomus tumors, whereas subtotal devascularization was achieved in jugular paragangliomas. In this latter location, the injection of acrylic glue was limited by the potential risk of reflux into normal brain territory via feeders from the internal carotid or vertebral artery. The tumors were surgically removed and histologically examined. No technical or clinical complications related to the embolization procedure occurred. CONCLUSION: Percutaneous puncture of paragangliomas in the head and neck region and their preoperative devascularization by intralesional injection of acrylic glue is a feasible, safe, and effective technique.

Adolescent↗
PubMed1990

[A case of Stewart-Treves syndrome--treatment with recombinant interleukin 2 and a review of Japanese literature].

A 76-year-old woman developed angiosarcoma 11 years after a radical mastectomy in the chronic lymphedema of the ipsilateral arm, referred to as Stewart-Treves syndrome. The patient was treated by intravenous and intralesional injection of recombinant interleukin 2 (rIL-2; TGP-3, Takeda Chemical Industries, LTD, Osaka). Intralesional injection was more effective than systemic administration. After a month, the lesion where the local injection was done showed little tumor cells with a dense infiltrate composed of lymphoid cells. It was observed that NK activity, LAK activity and IL-2 receptor positive T-cells in the peripheral blood increased during the administration of rIL-2. As the lesion was too large to be treated with rIL-2 alone, radiotherapy was performed. But the patient had no remarkably improvement and died 16 months later from the onset. Immunotherapy with rIL-2 can be useful for angiosarcoma and more effective regimen of rIL-2 is a important problem.

Aged↗
PubMed1984

Antitumor activity of deoxyribonucleic acid fraction from Mycobacterium bovis BCG. I. Isolation, physicochemical characterization, and antitumor activity.

A fraction extracted from Mycobacterium bovis strain BCG, which was composed of 70.0% DNA, 28.0% RNA, 1.3% protein, 0.20% glucose, and 0.1% lipid and of no detectable amounts of cell wall components such as alpha, epsilon-diaminopimelic acid and hexosamine, was found to possess strong antitumor activity. Repeated intralesional injection of this fraction, designated MY-1, without attachment to oil or a single intralesional injection of MY-1 emulsified in mineral oil caused the IMC carcinoma of CDF1 mice and line 10 tumor of strain 2 guinea pigs to regress and/or prevented metastasis very effectively. MY-1 after digestion with RNase, which contained 97.0% single-stranded DNA with a guanine-cytosine content of 69.8%, was more effective than undigested MY-1 against IMC and line 10 tumor, while MY-1 digested with DNase, which contained 97.0% RNA, had reduced activity, suggesting that the DNA from BCG possessed strong antitumor activity under certain conditions. Details of the extraction procedures and physicochemical characterization of MY-1 were also described.

Animals↗
PubMed1994

Intradermal bleomycin injections into normal human skin. A histopathologic and immunopathologic study.

BACKGROUND: Intralesionally injected bleomycin is a useful agent for the treatment of recalcitrant warts. The mechanism of action in wart therapy has been thought to be due to DNA and antiviral effects. To further characterize the inflammatory response to intralesional bleomycin injections, we examined the clinical, histologic, and immunopathologic response to intradermal bleomycin injections in normal human skin. RESULTS: Four volunteers were each given four intradermal bleomycin injections (0.01 to 0.5 U/mL) into normal human skin to establish a dose response. These injections induced a localized time and dose-dependent inflammatory reaction and persistent postinflammatory hyperpigmentation. Nine biopsy specimens from two volunteers were taken at different time points after intradermal bleomycin injections (0.1 to 1.0 U/mL) into normal human skin. Routine histologic study demonstrated dyskeratosis and necrosis of epidermal keratinocytes and eccrine epithelium associated with a prominent neutrophilic infiltrate, closely resembling histopathologic findings seen in neutrophilic eccrine hidradenitis. Expression of HLA-DR and intercellular adhesion molecule 1 was induced on keratinocytes; intercellular adhesion molecule 1 was upregulated, and endothelial leukocyte adhesion molecule 1 was induced on superficial dermal blood vessels. CONCLUSIONS: These findings suggest that intradermal bleomycin injection is either directly or indirectly cytotoxic to keratinocytes and eccrine epithelium. Expression and upregulation of activation antigens and cell adhesion molecules suggest that a cellular immune system response and proinflammatory cytokine secretion occur after intralesional bleomycin injection into normal human skin. Histopathologic findings at some injection sites resemble neutrophilic eccrine hidradenitis.

Biopsy↗
PubMed1995

Interstitial chemotherapy of experimental brain tumors: comparison of intratumoral injection versus polymeric controlled release.

Interstitial chemotherapy with controlled release polymers is a clinical adjunct in the management of malignant gliomas. The need for polymer to release the chemotherapeutic drug rather than simply injecting the drug into the tumor warrants further investigation. Therefore, we compared the effects of direct intralesional injection of carmustine (BCNU) and 4-hydroperoxycyclophosphamide (4HC) into the rat brain tumor bed with those from the same agents delivered via controlled release polymers implanted intracranially. Treatment was initiated on the fifth day after intracranial implantation of 9L gliosarcoma into male rats; two doses of each drug were injected intratumorally, representing either the amount of drug typically released in vivo from polymer during the first 24 h, or the maximal drug loaded on each polymer. Control rats were treated with empty polymers. We found that the median lifespan was extended in the groups of rats treated with intratumoral injection of BCNU (23% and 36% for 1 mg and 2 mg doses), and 271% with BCNU-impregnated polymer. Similar results were found with intratumoral 4HC (21% and 36% for 0.1 mg and 2 mg injection doses), and 121% with 4HC-impregnated polymer. Overall survival after intraneoplastic injections, however, was not statistically significantly different from that of control rats (p > 0.05). Furthermore, improvement in survival was not consistent, and some animals subjected to 4HC injection died early in the course of treatment. Polymeric treatment resulted in statistically significant prolongation of survival, compared to control rats (p < 0.001 for both BCNU and 4HC). We concluded that direct intralesional injection of BCNU and 4HC is less effective than controlled release via polymers for the treatment of 9L gliosarcoma in the rat model.

Animals↗
PubMed2002

Intralesional verapamil for the treatment of Peyronie's disease: a review.

Multiple treatment options have been used for Peyronie's disease (PD) including intralesional injection of the calcium antagonist verapamil. The use of verapamil is based on its capacity to alter fibroblast function at several levels, including cell proliferation, extracellular matrix protein synthesis and secretion, as well as collagen degradation. Consequently, calcium antagonists may have the capacity to slow, prevent, or even reverse plaque formation and the progression of PD. The multicenter international experience with intralesional verapamil injection suggests that the majority of men with PD that receive treatment demonstrate durable reduction in pain, decrease in curvature, and improved sexual function. We review the scientific rationale, published literature, clinical experience, and technique of intralesional injection of verapamil.

Calcium Channel Blockers↗
PubMed1980

Successful treatment of keratoacanthoma with intralesional fluorouracil.

Forty-one keratoacanthomas (KA) occurring in thirty patients were treated with weekly intralesional injections of 5-fluorouracil (5-FU). Forty lesions cleared after an average of three injections in an average of 3.4 weeks (range, 2 to 6 weeks). This response suggests that intralesional injections of 5-FU are the treatment of choice for KAs.

Adult↗