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Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunity.

BACKGROUND: Sustained intratumoral cytokine release using poly-lactic acid microspheres (PLAMs) can induce a systemic immune response, shifting immunotherapy to the neoadjuvant setting. METHODS: C57BL6 mice with established B16 melanomas underwent a single intralesional injection of IL-12, TNF-alpha or GM-CSF PLAM, alone or in combination. Tumor draining lymph nodes (TDLN) and spleens were assessed for a specific anti-tumor response by IFNgamma release assay and ELISPOT. RESULTS: Intralesional injection of TNF-alpha, alone or in combination, resulted in significant tumor ablation. The induction of tumor specific reactive T-cells in the TDLN was greatest with IL-12 and TNF-alpha. Only mice treated with IL-12 and TNF-alpha demonstrated a substantial T-cell response in cultured splenocytes. This combination resulted in a significant reduction in new tumors after re-challenge. Adjuvant therapy, using irradiated B16 cells in combination with equivalent doses of IL-12 and TNF-alpha, failed to generate a similar T-cell response or prevent re-challenge. CONCLUSIONS: Intratumoral IL-12 and TNF-alpha loaded PLAM leads to both local eradication of tumor and the induction of specific anti-tumor T-cells in the lymph nodes and spleens, resulting in memory immune response. Neoadjuvant treatment was significantly superior to postoperative autologous cellular vaccines using IL-12 and TNF-alpha PLAM.

Animals↗

A new therapeutic concept for the treatment of cystic hygroma.

A new therapeutic concept for the treatment of cystic lymphangioma (cystic hygroma) is presented. It consists of intralesional injection of triamcinolone (10 mg/kg) and surgical excision at a second stage if necessary. Four cases are presented to demonstrate the clinical application of this new therapeutic modality. Only in one case it was necessary to perform surgical excision as a second stage procedure, whereas three cases were successfully managed by intralesional injection of triamcinolone alone.

Child, Preschool↗

Intralesional infiltration of corticosteroids in the treatment of localised langerhans' cell histiocytosis of the mandible Report of known cases and three new cases.

Langerhans' cell histiocytosis (LCH) can involve virtually any site and organ of the body, either as an isolated lesion or as a widespread systemic disease. Bone can be involved as a part of generalised disease or as a separate entity, formerly known as eosinophilic granuloma. The clinical cause of localised LCH (LLCH) to bone is generally benign. Solitary bone lesions may resolve spontaneously after diagnostic biopsy in a period of months to years. If treatment is indicated, as in larger lesions with pain, swelling and risk for spontaneous fracture, the disease can be controlled by chemotherapy or local measures such as surgical curettage, low-dose radiotherapy and intralesional injection of corticosteroids. There are no controlled studies in the literature comparing outcomes of these treatment modalities because of low incidence of the disease and general tendency to regress. Three patients (female, 28 months; male, 9 years; male, 15 years) with LLCH of the mandible were treated in an one stage procedure with intralesional injection of 80, 40 and 80 mg methylpredisolone succinate, respectively, as the primary form of treatment. Patients were seen for clinical and radiological evolution 1, 3, 6, 9 and 12 months after treatment, and yearly thereafter. The overall outcome was excellent. The lesions showed clinically and radiologically complete remission approximately 6 months after treatment. There were no complications nor morbidity of the treatment. After a follow-up period of 12 months, the patients are well with no evidence of residual disease on radiographs. Local injection of corticosteroids should be the initial choice of treatment of LLCH of the mandible, because of the favourable treatment outcome in this disease and possible complications and lasting effects of surgery, radiotherapy and chemotherapy.

Adolescent↗

Artecoll granuloma: a rare adverse reaction induced by microimplant in the treatment of neck wrinkles.

BACKGROUND: Artecoll is now being widely used as an injectable aesthetic microimplant for the treatment of wrinkles because of its long-lasting cosmetic effects and the rarity of late complications, including foreign body granulomas. Recently, however, several cases of Artecoll-induced granulomas on the face have been reported, especially in patients receiving overly superficial or overly correcting implants. METHODS AND RESULTS: A 50-year-old Korean woman who had been treated with Artecoll for the correction of the neck wrinkles presented 4 years later with an extensive Artecoll-induced foreign body granuloma along the injection sites in the neck. After three intralesional injections of triamcinolone acetonide, the lesions had almost disappeared. CONCLUSION: To our knowledge, this case is the first report of an extensive Artecoll-induced granuloma on the neck. Our findings suggest that Artecoll not be used as implant material in thin and constantly movable skin, such as that of the neck.

Anti-Inflammatory Agents↗

3.5-Year follow-up of intralesional cidofovir protocol for pediatric recurrent respiratory papillomatosis.

OBJECTIVES: Intralesional injection of cidofovir has been described as an adjunctive treatment for pediatric recurrent respiratory papillomatosis (RRP). However, questions remain regarding the optimal dosing schedule and side-effect profile. The objective of this study was to describe patient outcomes following a standardized cidofovir protocol. METHODS: Eleven pediatric patients originally treated with a standardized stepped-dose protocol of intralesional cidofovir for RRP were followed for an extended observational period. Additional interventions, disease severity, and adverse outcomes were recorded. RESULTS: Five of 11 patients have required no further treatments following the original cidofovir protocol. Two patients initially achieved remission but have subsequently required additional treatment for recurrent disease. Four patients never achieved remission and have undergone multiple additional interventions. Mean follow-up time for all patients from the conclusion of the original study was 30.2 months (10-45). No adverse outcomes were noted. CONCLUSIONS: Intralesional injection of cidofovir may have some potential as an adjunct in the treatment of RRP. Response to cidofovir is unpredictable. Further study of cidofovir is necessary to more clearly define whether the favorable responses observed represent a true treatment effect or simply reflect the natural history of the disease. Perhaps as important is to refine treatment protocols and informed consents that reflect the concern about the carcinogenic potential of cidofovir and to better characterize the drug's side-effect profile.

Adolescent↗

Intralesional verapamil injection for the treatment of Peyronie's disease.

Peyronie's disease remains a therapeutic dilemma for the practicing urologist. Multiple nonoperative therapies have been offered with variable suboptimal response rates. Calcium channel blockers have been shown to alter the metabolism of fibroblasts, resulting in decreased extracellular matrix secretion of collagen as well as increased collagenase activity. In this nonrandomized dose-escalating format study 14 men received biweekly injections of verapamil into the Peyronie's plaques for 6 months. Subjectively, there was significant improvement in plaque-associated penile narrowing (100%) and curvature (42%). Objectively, a decreased plaque volume of greater than 50% was noted in 30% of the subjects. Plaque softening was noted in all patients, while 83% noticed that plaque-related changes in erectile function had arrested or improved. There was no toxicity nor did symptoms recur when improvement was noted. This preliminary study suggests that intralesional calcium antagonist (verapamil) therapy offers an economical and sensible nonoperative approach to the treatment of Peyronie's disease.

Adult↗

[Study on type I and type III procollagen mRNA and in situ collagen proteins expressions in hypertrophic scars after intralesional Kenalog treatment].

OBJECTIVE: This is to investigate the mechanism of effects of Kenalog on type I and III collagen syntheses and degradation in hypertrophic scars. METHODS: Intralesional injection of Kenalog was performed on 6 patients with hypertrophic scars. On the 3rd day and 7th day after the treatment, 6 samples from the 6 patients each were collected and type I and III collagen proteins and in situ procollagen mRNA expressions were studied by means of immunohistochemistry and molecular biology. RESULTS: On the 7th day after intralesional injection of Kenalog, type I collagen proteins reduced (P < 0.05) and type III collagen proteins did not reduced significantly (P > 0.05). On the 3rd day after intralesional injection of Kenalog, both type I and type III procollagen mRNA expressions were significantly inhibited and on the 7th day both procollagen mRNA expressions decreased further. CONCLUSIONS: Intralesional Kenalog may inhibit type I procollagen mRNA expression more than type III. Gene expressive intensions of type I and III procollagen were higher in hypertrophic scars than in normal skin.

Adolescent↗

OK-432 therapy for lymphatic malformation in 32 patients (28 children).

BACKGROUND/PURPOSE: Operating lymphatic malformation (LM) may lead to nerve damage with permanent cosmetic disturbance. Even sclerosants as ethanol and Sotradecol may sometimes harm more than cure. The purpose with this study was to evaluate the effect of a relatively new drug for intralesional injections, OK-432. METHODS: The diagnosis of LM was made clinically by means of ultrasound and MRT and/or CT. Thirty-two patients (28 children) with LM were consecutively enrolled in the study. Twenty-nine (27 children) had not been treated previously: 17 (15 children) had macrocysts (MAC), four microcysts (MIC) and eight had combined cysts (CC). Three patients (one child) had got previous treatment without any curative effect. All patients got intralesional injections with OK-432 at intervals according to a previously published protocol (Läkartidningen, 95 (1998) 2074). RESULTS: No serious adverse effects were seen. The results obtained were excellent in all with macrocysts but in one, who was pretreated with ethanol, where no LM-regression was seen. None of four with MIC-LM required further therapy; for two of them the results were excellent. Of 10 with CC, seven showed excellent results. Only one required surgery. CONCLUSION: OK-432 is effective and is proposed to be the first choice of treatment for LM.

Adolescent↗

Intralesional cis-diamminedichloroplatinum and purified collagen treatment of human metastatic malignancies: a feasibility study.

A feasibility study of the treatment of advanced superficial human malignant tumors utilizing direct intralesional injections of cisplatin mixed with purified bovine collagen was performed. The purpose of using intralesional injection of cisplatin mixed with collagen was to limit the drug exposure to normal tissues while increasing the dose and duration of exposure to the tumor. Fourteen evaluable superficial tumors in four patients (melanoma, breast CA, squamous CA from larynx) received a total of 65 treatments in the outpatient clinic setting. All patients had failed prior treatment with systemic intravenous cisplatin. Lesions were treated at least three times at two-week intervals. After intramuscular meperidine premedication, multiple injections of cisplatin mixed with collagen were made into the tumors. There was minimal normal tissue toxicity and minimal systemic toxicity. Tumor regression or stabilization occurred in 86% (12/14) of tumors; 50% (7/14) of lesions regressed more than 50% in size. This study suggests that intralesional colloidal cisplatin can overcome resistance to systemic intravenous cisplatin.

Adenocarcinoma↗

[Aneurysmal bone cyst of the cranial base treated by partial resection and calcitonin injection. A case report].

STUDY DESIGN: First published report of a cranial aneurysmal bone cyst (ABC) treated successfully with intralesional injection of calcitonin. OBJECTIVES: To describe a safe and effective treatment method for ABCs of the cranial base. SUMMARY OF BACKGROUND DATA: ABC is a rare form of dystrophic pseudotumor. Less than 100 cases involving the skull have been reported in the literature, most of them localised in the cranial vault. Cranial base locations are rare and difficult to treat. We selected this treatment after a very rapid recurrence of the lesion following a partial resection. Method. - After a partial resection of a 10 cm petro-occipital ABC that encased the vertebral artery and the lower cranial nerves, an Ommaya reservoir was implanted with a catheter tip inside the ABC. Repeated intralesional injections of calcitonin were performed through the reservoir. RESULTS: Shrinkage of the cyst occurred with disappearance of its heterogeneous cystic content and ossification of its walls. There was no complication and the lesion remains quiescent at a 3 year follow-up. CONCLUSION: We reviewed the pertinent literature concerning percutaneous treatment of ABC. The percutaneous intralesionnal injection of calcitonin was reported in the literature only in 3 publications reporting 9 cases that did not involve the skull. This treatment seems safe and effective, worthy in cranial base ABCs that are difficult to resect completely.

Adolescent↗

Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin.

Intralesional injection of BCG into an established line-10 hepatocellular carcinoma in the strain-2 guinea pig causes regression of the tumor and induction of line-10 immunity. We found that the animals were already protected for a second challenge with line-10 tumor cells 7 days after BCG treatment. We studied whether this early induction of immunity was correlated with the expression of MHC class II antigens on line-10 tumor cells and was correlated with an increased expression of MHC class II antigens on leukocytes in the primary tumor and in the regional lymph node (Ln. axillaris accessorius). The MHC class II antigens and the leukocyte subpopulations were measured with monoclonal antibodies and flow cytofluorometry. In the draining lymph node the number of nucleated cells increased about 10-fold during the first 5 days after intralesional injection of BCG. At this time the MHC class II antigen expression of these cells was increased from 21%-32% in the naive controls to 39%-53% in animals with BCG-treated tumors. This implies that the number of MHC-class-II-positive cells increased about 20-fold in the draining lymph node. Surprisingly, the increase in percentage of MHC-class-II-antigen-positive cells was mainly due to an increase of IgM-positive B cells from 8%-11% to 22%-41% and an increase of IgG-positive B cells from 7%-27% to 25%-44%. In the tumor, BCG treatment induced a small increase of MHC-class-II-antigen-positive cells from 11%-12% to 15%-20%. Probably this increase came not from tumor cells but mainly from a BCG-induced infiltration of mononuclear cells, as an increase of T cells from 14% to 20%, an increase of macrophages from 8% to 18%, and an increase of B cells from 0 to 6% was observed. We conclude that the potentiation of anti-(line-10 tumor cell) immunity correlated with a 20-fold increase of MHC-class-II-antigen-positive cells in the lymph nodes and a small increase in the number of MHC-class-II-antigen-positive tumor-infiltrating cells.

Animals↗

Liposome-mediated gene transfer into human basal cell carcinoma.

Direct intralesional injection of DNA encoding interferon-alpha2 (IFN-alpha2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%). Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha2 using this method resulted in sustained production of IFN-alpha2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC.

Adult↗

OK-432 therapy in 64 patients with lymphangioma.

Intralesional injection of OK-432 was employed to treat 64 lymphangiomas between 1986 and 1992. This was used as primary therapy for 46 lesions (group A), as treatment following incomplete surgical removal in 14 (group B), and as therapy after failure of bleomycin in 4 (group C). In group A (n = 46), total shrinkage of the lesion, without serious complications, was noted in 23; there was marked shrinkage in 8, slight shrinkage in 12, and no response in 3. Of the cystic lesions (n = 24), significant shrinkage occurred in 22; of the cavernous lesions (n = 22), only 9 improved after treatment. In groups B (n = 14) and C (n = 4) there was significant clinical improvement occurred in 5 and 2, respectively. No recurrence was noted during follow-up (6 to 87 months). The only side effects were fever lasting 2 to 4 days and a local inflammatory reaction of 3 to 7 days' duration. The local inflammation did not cause any damage to the overlying skin and did not lead to scar formation. These data suggest that intralesional injection of OK-432 is effective treatment for lymphangiomas and should be considered as the primary method of treatment.

Humans↗

Musculoskeletal clinic in general practice: study of one year's referrals.

BACKGROUND: A musculoskeletal clinic, staffed by a general practitioner trained in osteopathy, medical acupuncture and intralesional injections, was set up in an inner London general practice in 1987. AIM: A retrospective study was undertaken of one year's referrals to the clinic in 1989-90 to determine how general practitioners were using the clinic in terms of problems referred; consultation patterns of patients attending the clinic and 12 months after initially being seen; and how access to the clinic influenced referrals to relevant hospital departments. METHOD: Day sheets were studied which recorded information on demographic characteristics of patients referred to the clinic and their problems, diagnoses made, duration of symptoms, number and range of treatments given, and recurrence of problems. Use of secondary referral sources was also examined. RESULTS: During the study year 154 of 3264 practice patients were referred to the musculoskeletal clinic, and attended a mean of 3.5 times each. Of all the attenders 64% were women and 52% were 30-54 years old. Eighty one patients (53%) presented with neck, back or sciatic pain. A specific traumatic, inflammatory or other pathological process could be ascribed to only 19% of patients. Regarding treatment, 88% of patients received osteopathic manual treatment or acupuncture, or a combination of these treatments and 4% received intralesional injections. Nine patients from the clinic (6%) were referred to an orthopaedic specialist during the year, two with acute back pain. Referrals to orthopaedic specialists by the practice as a whole were not significantly lower than the national average, although the practice made fewer referrals to physiotherapy and rheumatology departments than national figures would have predicted. Seventeen patients (11%) returned to the clinic with a recurrence of their main complaint within a year of their initial appointment; second courses of treatment were usually brief. CONCLUSION: The clinic encouraged a relatively low referral rate to musculoskeletal specialists outside the practice. However, a need was identified for better communication about the potential of the approaches used in order that referrals to secondary specialists, particularly orthopaedic specialists, could be further reduced.

Acupuncture Therapy↗

Treatment of cutaneous T cell lymphoma with low doses of interferon alpha-2b.

OBJECTIVE: To evaluate the optimal dose and route of interferon-alpha-2b (INF-alpha-2b) given to the Chinese patients with cutaneous T-cell lymphomas (CTCL). PATIENTS AND METHODS: Sixteen Chinese patients with CTCL treated with INF-alpha-2b were evaluated. They were divided into groups according to the TNM Classification: I B (8 patients), II A (2), II B (5) and IV B (1). During induction INF-alpha-2b was given intramuscularly every other day or two times a week, beginning with a dose of 1-3 x 10(6) IU. Depending on tolerance, the dosage could be increased weekly to a maximum tolerated dose of 18 x 10(6) IU (mean, 6 x 10(6) IU/week) with administration two or three times a week. Patients with clinical response were given maintenance dosage from the start. Thereafter the dosage was gradually decreased after disappearance of skin lesions. Three patients were treated by combining intramuscular and intralesional injection of INF. RESULTS: Six patients (I B, 2 patients: II A, 2, II B, 2) achieved complete response (CR). Seven patients (I B, 5 patients) showed partial response. The overall response rate in this group was 81.25%. The prominent initial clinical response in three patients was manifested early at one week after intramuscular treatment with INF and then the skin lesions were resistant to the therapy but disappeared rapidly by combining intralesional injection of INF. The conditions of those patients obtaining CR within 3 to 6 weeks were stable for 1-36 weeks. CONCLUSIONS: This study had demonstrated that the overall response rate in treatment of patients with CTCL was 81.25% and higher (85.7%-87.5%) in the subgroups at early stages I and II of the disease. The dosage (mean dose of 6 x 10(6) IU/week) adopted by us is optimal for the Chinese patients with CTCL. Intralesional injection of INF could be recommended.

Adult↗

Augmentation of cytotoxicity of tumor-infiltrating lymphocytes by biological response modifiers.

Lymphocyte infiltration into a tumor has been regarded as an expression of host immunity against cancer, but tumor-infiltrating lymphocytes (TIL) have little or no cytotoxicity. This study examined two different approaches to augment this low cytotoxicity. Firstly, biological response modifiers (OK-432, PSK) were injected into gastric cancer intralesionally. Intralesional injection of OK-432 or PSK significantly augmented the cytotoxicity of TIL. By the injection of OK-432, the ratio of OKT8-, Leu7-positive cells were increased in the TIL subset. In the second approach, TIL of gastric or pulmonary cancer patients were cultured with interleukin-2 (IL-2) in vitro. Co-culturing with IL-2 augmented the low cytotoxicity of TIL, and broad-reactive lymphokine-activated killer (LAK) cells were generated from TIL.

Cytotoxicity, Immunologic↗

Intralesional BCG injection of pulmonary neoplasms: radiographic findings.

A clinical trial has been established to evaluate the use of intralesional bacillus Calmette Guérin (BCG) immunotherapy as an adjunct to surgery in resectable pulmonary neoplasms. BCG was injected percutaneously under fluoroscopic guidance into a single nodule in each of 21 patients with resectable primary and metastatic pulmonary neoplasms. Eighteen of 21 infected nodules increased in size and nine became poorly defined in the 2-4 week interval between BCG administration and resection. There was no change in those nodules that were not injected. The changes in the injected nodules were due to BCG-induced granulomatous inflammation and necrosis. BCG can be administered intralesionally into pulmonary neoplasms without significant complications (pneumothorax in nine, intrapleural injection in one). Preliminary observations suggest an improvement in disease-free interval. A prospective, randomized trial is planned to determine whether BCG immunotherapy will result in significantly improved survival in patients with primary and metastatic pulmonary neoplasms.

Adolescent↗

Correction of the soft tissue pollybeak using triamcinolone injection.

OBJECTIVE: To describe the technique for correction of the soft tissue pollybeak deformity using intralesional injection of triamcinolone acetonide. METHODS: We discuss our philosophy, regimen, and technique for treatment of the soft tissue pollybeak using triamcinolone injection. We include results from a series of 173 patients who underwent rhinoplasty performed by one of us (N.J.P.). RESULTS: Triamcinolone was injected at 1 week after surgery in 127 patients (73%). A second injection was performed in 92 (72%) of the 127 patients at 4 weeks after surgery. One hundred eight (85%) of the 127 patients had an acceptable result, as judged by the surgeon, with good supratip definition. Nineteen (15%) of the 127 patients had a less than optimal result, with residual supratip fullness, as judged by the surgeon. There were no complications caused by triamcinolone injection. CONCLUSIONS: Because revision surgery is difficult and may be associated with complications, intralesional triamcinolone injection is the first-line treatment for the soft tissue pollybeak deformities caused by subdermal scarring. Should intralesional steroid injection fail to satisfactorily treat the deformity, revision rhinoplasty can subsequently be performed.

Adolescent↗