Intraluminal infusion of Penta-Galloyl Glucose reduces abdominal aortic aneurysm development in the elastase rat model.

BACKGROUND: An abdominal aortic aneurysm (AAA) is a progressive chronic dilatation of the abdominal aorta with terminally rupture when the aortic wall is so weakened that aortic wall stress exceeds wall strength. No effective medical treatment exists so far. We aimed to test whether intraluminal admission of Penta-Galloyl Glucose (PGG) treatment in a rodent AAA model could hold the potential to inhibit aneurysmal progression. METHOD: Male Sprague Dawley rats had either intraluminal elastase infused for AAA induction or saline to serve as controls. In two independent experimental series, elastase was used to induce AAA followed by an intraluminal PGG (directly or by a drug eluting balloon) treatment. All rats were followed for 28 days and euthanized. In both series, maximal infrarenal aortic diameter was measured at baseline and at termination as a measure of AAA size. In series 2, maximal internally AAA diameter was followed by ultrasound weekly. AAA tissues were analyzed for elastin integrity by millers stain, collagen deposition by masson trichrome staining. In other AAA tissue samples the mRNA level of CD45, lysyloxidase (LOX), lysyloxidase like protein 1 (LOXL1) were determined by qPCR. RESULTS: Direct administration of PGG significantly reduced AAA expansion when compared to controls. PGG treatment resulted in a higher number and more preserved elastic fibers in the aneurysmal wall, while no significant difference was seen in the levels of CD45 and LOX mRNA levels. The drug eluting balloon (DEB) experiment showed no significant difference in AAA size observed neither macroscopically nor ultrasonically. Also the aneurysmal mRNA levels of CD45, LOX and LOXL1 were unchanged between groups. CONCLUSION: A significant reduced expansion of AAAs was observed in the PGG group, suggesting PGG as a drug to inhibit aneurysmal progression, while administration through a DEB did not show a promising new way of administration.

Pressure-enabled delivery of gemcitabine in an orthotopic pancreatic cancer mouse model.

BACKGROUND: We describe the use of pancreatic retrograde venous infusion in an orthotopic murine model of pancreatic ductal adenocarcinoma and hypothesize that pancreatic retrograde venous infusion delivery of gemcitabine will increase concentrations of gemcitabine in the tumor and the subsequent tumor response to treatment. METHODS: Murine pancreatic ductal adenocarcinoma (KPC4580P) was transplanted onto the pancreatic tail of C57BL/6J mice. Groups (n = 15) of mice were assigned to sham laparotomy and 100 mg/kg intraperitoneal infusion of gemcitabine (systemic gemcitabine), pancreatic venous isolation with pancreatic retrograde venous infusion of 100 mg/kg gemcitabine, or pancreatic retrograde venous infusion with saline infusion. Tumor pressures were recorded during pancreatic retrograde venous infusion. Mice were killed at 1 hour or 7 days after infusion. RESULTS: Baseline tumor pressures were 45 ± 8 mm Hg, and pancreatic retrograde venous infusion increased tumor pressures by 29 ± 6 mm Hg (P < .01). Pancreatic retrograde venous infusion gemcitabine mice had greater tumor gemcitabine concentrations compared with systemic gemcitabine (127 vs 19 ng/mg; P < .01) and lesser tumor volumes compared with both systemic gem and pancreatic retrograde venous infusion with saline (274 vs 857 vs 629 mm3; P < .01). CONCLUSION: Pancreatic retrograde venous infusion increased tumor pressures greater than baseline, improved gemcitabine delivery, and increased the treatment response. These findings suggest that pressurized, regional delivery overcomes the increased pressure barrier in pancreatic ductal adenocarcinoma. Additional preclinical studies with cytotoxic and immunotherapeutic agents and clinical trials using pressure-enabled drug delivery with pancreatic retrograde venous infusion devices are underway.

Phase I trial of convection-enhanced delivery of IL13-Pseudomonas toxin in children with diffuse intrinsic pontine glioma.

OBJECTIVE In this clinical trial report, the authors analyze safety and infusion distribution of IL13-Pseudomonas exotoxin, an antitumor chimeric molecule, administered via intratumoral convection enhanced delivery (CED) in pediatric patients with diffuse intrinsic pontine glioma (DIPG). METHODS This was a Phase I single-institution, open-label, dose-escalation, safety and tolerability study of IL13-PE38QQR infused via single-catheter CED into 5 pediatric DIPG patients. IL13-PE38QQR was administered to regions of tumor selected by radiographic findings. Two escalating dose levels were evaluated: 0.125 µg/mL in cohort 1 and 0.25 µg/mL in cohort 2. Real-time MRI was performed during intratumoral infusions, and MRI and MR spectroscopy were performed before and after the infusions. Clinical evaluations, including parent-reported quality of life (QOL), were assessed at baseline and 4 weeks post-infusion. RESULTS Direct infusion of brainstem tumor with IL13-PE using the CED technique in patients with DIPG produced temporary arrest of disease progression in 2 of 5 patients, both of whom subsequently received a second infusion. All 5 patients showed signs of disease progression by 12 weeks after initial infusion. Two patients experienced transient cranial nerve deficits and lethargy after infusion, and these deficits resolved with corticosteroid treatment in both cases. No patient had radiographic evidence of acute or long-term treatment toxicity. Parent-reported QOL was consistent with medical outcomes. CONCLUSIONS Even though IL13-PE delivered by CED did not reach the entire MRI-defined tumor volume in any patient, short-term radiographic antitumor effects were observed in 2 of the 5 patients treated. The patients' performance status did not improve. Drug delivery using multiple catheters may produce improved outcomes. Clinical trial registration no.: NCT00088061 (clinicaltrials.gov) ABBREVIATIONS CED = convection-enhanced delivery; DIPG = diffuse intrinsic pontine glioma; IL-13 = interleukin 13; IL13R = IL-13 receptor; IPI = Impact of Pediatric Illness; KPS = Karnofsky Performance Status; LPS = Lansky Performance Status; MRS = MR spectroscopy; NAA = n-acetyl aspartate; QOL = quality of life; Vd = volume of distribution; Vi = volume of infusion.

Treatment of gastric GIST using endoscopic techniques combined with the application of endoloop and intralesional cyanoacrylate in a non-surgical patient

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Efficacy of continuous in-wound infusion of levobupivacaine and ketorolac for post-caesarean section analgesia: a prospective, randomised, double-blind, placebo-controlled trial.

BACKGROUND: In-wound catheters for infusion of local anaesthetic for post-caesarean section analgesia are well tolerated in parturients. Few studies have examined continuous in-wound infusion of a combination of local anaesthetic and non-steroidal anti-inflammatory drug for post-caesarean section analgesia. This single centre study evaluated post-operative analgesic efficacy and piritramide-sparing effects of continuous in-wound infusion of either local anaesthetic or non-steroidal anti-inflammatory agent, or the combination of both, versus saline placebo, when added to systemic analgesia with paracetamol. METHODS: After National Ethical Board approval, 59 pregnant women scheduled for non-emergency caesarean section were included in this prospective, randomised, double-blind, placebo-controlled study. The parturients received spinal anaesthesia with levobupivacaine and fentanyl. Post-operative analgesia to 48 h included paracetamol 1000 mg intravenously every 6 h, with the studied agents as in-wound infusions. Rescue analgesia with piritramide was available as needed, titrated to 2 mg intravenously. Four groups were compared, using a subcutaneous multi-holed catheter connected to an elastomeric pump running at 5 mL/h over 48 h. The different in-wound infusions were: levobupivacaine 0.25% alone; ketorolac tromethamine 0.08% alone; levobupivacaine 0.25% plus ketorolac tromethamine 0.08%; or saline placebo. The primary outcome was total rescue piritramide used at 24 h and 48 h post-operatively, under maintained optimal post-caesarean section analgesia. RESULTS: Compared to placebo in-wound infusions, ketorolac alone and levobupivacaine plus ketorolac in-wound infusions both significantly reduced post-operative piritramide consumption at 24 h (p = 0.003; p < 0.001, respectively) and 48 h (p = 0.001; p < 0.001). Compared to levobupivacaine, levobupivacaine plus ketorolac significantly reduced post-operative piritramide consumption at 24 h (p = 0.015) and 48 h (p = 0.021). For levobupivacaine versus ketorolac, no significant differences were seen for post-operative piritramide consumption at 24 h and 48 h (p = 0.141; p = 0.054). CONCLUSION: Continuous in-wound infusion with levobupivacaine plus ketorolac provides greater opioid-sparing effects than continuous in-wound infusion with levobupivacaine alone. TRIAL REGISTRATION: German Clinical Trials Register: retrospectively registered on 30 July, 2014, DRKS 00006559 .

Cidofovir intralesional en infección por el virus del papiloma humano en espacios interdigitales / Intralesional cidofovir in human papilomavirus infection in interdigital spaces

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Application of Convection-Enhanced Drug Delivery in the Treatment of Malignant Gliomas.

Convection-enhanced delivery (CED) is a promising new method of local drug delivery therapy for a diverse type of antitumor agents. CED offers significant advantages over systemic chemotherapy by bypassing the blood-brain barrier and obtaining adequate drug concentration with limited systemic toxicity. Actually, there is no effective treatment of malignant gliomas (MGs); survival rates remain poor despite decades of clinical trials. Conventional chemotherapy has been found to be minimally effective in the control of MG progression. CED involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered directly to the tumor using continuous, low-positive-pressure bulk flow. On the basis of the preclinical and clinical studies, we demonstrated that CED could produce effective drug delivery to large brain and tumor areas. However, clinical studies to date have not found any substantial improvement in overall survival in the treatment of MG. This overview presents up-to-date clinical results in the treatment of MG by the application of CED.

The efficacy and safety of hepatic arterial infusion of oxaliplatin plus intravenous irinotecan, leucovorin and fluorouracil in colorectal cancer with inoperable hepatic metastasis.

Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85 mg/m(2) HAI plus systemic intravenous chemotherapy [leucovorin 200 mg/m(2), 5-FU 2400 mg/m(2) and irinotecan (IRI) 160 mg/m(2) in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.

Tratamento intralesional de malformações linfáticas com ênfase na escleroterapia com picibanil (OK-432): revisão sistemática / Intralesional treatment of lymphatic malformations with emphasis on Picibanil (OK-432) sclerotherapy: a systematic review

INTRODUÇÃO: Conduziu-se revisão sistemática retrospectiva da literatura incluindo estudos relatando o uso de picibanil para tratar malformações linfáticas (ML). MÉTODOS: A pesquisa foi realizada com estudos publicados no PubMed de janeiro de 1990 a 14 de abril de 2013. Na estratégia de busca, usou-se os descritores "OK-432" ou "Picibanil" e "lymphatic malformation". Os seguintes elementos foram comparados aos de outras modalidades relatadas e, então, compilados: mecanismo de ação, indicações, contraindicações, eficácia, administração, efeitos colaterais, complicações, vantagens e desvantagens. RESULTADOS: Foram encontrados 44 estudos, 27 dos quais atenderam aos critérios de inclusão. O picibanil é uma preparação liofilizada de uma cepa de baixa virulência de Streptococcus pyogenes inativada pela penicilina G. Seu mecanismo de ação ainda não definido claramente, mas especula-se que provoque uma resposta inflamatória controlada com adesão das paredes dos cistos. O picibanil é indicado quase que unanimemente para o tratamento da ML macrocística, cuja resposta é mais efetiva do que em lesões microcísticas ou mistas. Em geral, o picibanil é administrado por meio de punção com visualização direta ou guiada por ultrassonografia, com o paciente sob anestesia geral. A preparação comumente utilizada consiste em 0,1 mg de picibanil em 10 ml de soro fisiológico. Os efeitos colaterais são, em geral, leves; sendo dor, inchaço e febre os mais frequentemente relatados. CONCLUSÃO: Os estudos apresentam pouca evidência científica. A revisão sistemática identificou que o picibanil é útil no tratamento da ML de qualquer tipo, mas tem resultados melhores em lesões macrocísticas. A eficácia foi comparável à de outras terapias. Não foi apresentada nenhuma contraindicação específica. Embora o mecanismo de ação ainda não tenha sido determinado, o picibanil trata-se de opção de tratamento.

INTRODUCTION: We performed a retrospective systematic review of studies reporting the use of Picibanil for treatment of lymphatic malformations (LMs). METHODS: We searched the PubMed database for available studies, including those published between January 1990 and April 14, 2013. The search strategy involved the use of the keywords "OK-432" or "Picibanil" and "lymphatic malformation." Information was compiled regarding the reported mechanism of action, indications, contraindications, efficacy, administration, side effects, complications, and advantages and disadvantages compared to those of other modalities. RESULTS: Forty-four studies were found, of which 27 fulfilled the inclusion criteria. Picibanil is a lyophilized preparation of a low-virulence strain of Streptococcus pyogenes inactivated with penicillin G. Its mechanism of action is unclear, but it has been speculated that it causes a controlled inflammatory response with adhesion of cyst walls. Picibanil is almost unanimously indicated for the treatment of macrocystic LMs, which show a greater effectiveness response compared to that shown by microcystic or mixed LMs. Picibanil is usually administered by puncturing, either with direct visualization or guided by ultrasound, with the patient under general anesthesia. The most widely used preparation comprises 0.1 mg of Picibanil in 10 mL of saline. Side effects are mostly mild, with pain, swelling, and fever being the most frequently reported. CONCLUSION: The studies had low scientific evidence. A systematic review found that Picibanil is useful against any LM, with better results in macrocystic lesions. Efficacy was comparable to that of other therapies. No specific contraindication was presented. Although the mechanism of action has not been established, the inclusion of Picibanil as a treatment option is warranted.

Computed tomography-guided percutaneous focal catheter infusion in the treatment of spinal tuberculosis.

The study aimed to investigate the efficacy of computed tomography (CT)-guided percutaneous focal catheter infusion for the treatment of spinal tuberculosis. Clinical and follow-up data from 27 spinal tuberculosis patients who underwent CT-guided intervertebral catheterized infusion chemotherapy from May 2008 to October 2011 were retrospectively analyzed; treatment included pure intervertebral infusion chemotherapy and catheter drainage for continuous abscess washing during infusion chemotherapy. All surgeries were successfully completed under CT guidance without complications. The C-reactive protein levels of most patients rebounded within the first postoperative week but significantly decreased after the second and fourth postoperative weeks. CT-guided percutaneous focal catheter infusion was effective for the treatment of spinal tuberculosis and induced little trauma; this treatment could also relieve the symptoms and improve the quality of life of elderly patients with poor general conditions.

Retrograde chemoinfusion of the upper tract: standardizing the delivery of topical adjuvant therapy.

Upper tract urothelial carcinoma has a high recurrence rate after endoscopic treatment. Immediate postoperative topical chemotherapy may reduce recurrences, as in bladder cancer. A reliable delivery method to the upper tract does not exist. We propose a new infusion pump technology for the delivery of topical chemotherapeutic agents to the upper tract. With the patient under general anesthesia, contrast is infused into the upper collecting system using a standard infusion pump. An optimal infusion rate is determined based on fluoroscopic filling of the upper collecting system and transduced intrapelvic pressures. Using this rate, the infusion is repeated postoperatively with the chemotherapeutic agent. We report one case of successful execution to demonstrate proof of concept. We are the first to describe retrograde upper tract chemotherapeutic irrigation with an intravenous pump. This technique may facilitate and standardize the delivery of intracavitary chemotherapy. Further investigation to determine whether it translates into improved safety and/or efficacy is warranted.

Convection-enhanced delivery: from mechanisms to clinical drug delivery for diseases of the central nervous system.

The evolution of cancer chemotherapy has been a major advance in medical science in the late 20th century. However, patients with malignant gliomas have not benefitted much. The blood-brain barrier (BBB), which always hinders the entry of therapeutic agents into the central nervous system (CNS), may at least partly be responsible. Convection-enhanced delivery (CED), a method for distributing large and small molecular weight compounds bypassing the BBB, enables robust distribution of the infused molecules at the site of infusion. CED is promising as an effective treatment not only for malignant gliomas but also for multiple CNS disorders because this method can effectively distribute multiple molecules that are potentially effective against different diseases. Although the method is quite simple, several problems require solution in developing novel CED-based strategies, including what, where, when, and how to infuse. This review discusses basic considerations when developing CED-based strategies for CNS diseases, focusing mainly on brain tumors.

Ensayo clínico: la infiltración intralesional con metotrexato de forma neoadyuvante en la cirugía del queratoacantoma permite obtener mejores resultados estéticos y funcionales / Intralesional Infusion of Methotrexate as Neoadjuvant Therapy Improves the Cosmetic and Functional Results of Surgery to Treat Keratoacanthoma: Results of a Randomized Trial

Introducción: El queratoacantoma es considerado hoy día un carcinoma epidermoide in situ que aparece principalmente en pacientes mayores de 70 años. Se trata de un tumor de buen pronóstico que, en algunos casos, muestra resolución espontánea.El tratamiento de este tipo de tumoración es la exéresis simple. Sin embargo, la localización preferente en las regiones facial y acral, el tamaño y su rápido crecimiento son factores que hacen que la cirugía sea en algunos casos agresiva y antiestética. Objetivo: El objetivo principal del estudio es evaluar la eficacia de la infiltración intralesional de metotrexato en la reducción del tamaño prequirúrgico de la lesión y del correspondiente defecto quirúrgico resultante de la intervención. Material y métodos: Se realizó un estudio prospectivo aleatorizado en el que se incluyeron todos aquellos pacientes atendidos en nuestro Servicio diagnosticados de queratoacantoma de al menos 1,5cm de tamaño entre enero de 2009 y enero de 2010. Se establecieron dos grupos, uno en el que los pacientes recibieron una infiltración de metotrexato previamente al acto quirúrgico y otro en el que se realizó directamente la cirugía. Resultados: De los 25 pacientes incluidos en el estudio, 10 casos recibieron neoadyuvancia con metotrexato intralesional (grupo A) y 15 casos fueron intervenidos mediante cirugía aislada (grupo B).Los pacientes del grupo A mostraron una reducción en el tamaño tumoral en el momento de la cirugía que osciló entre un 50 y un 80%. Ninguno de los pacientes presentó complicaciones relacionadas con la inoculación del metotrexato ni con la intervención quirúrgica. En el grupo B sólo uno de los casos mostró una discreta disminución de sus dimensiones en el momento del acto quirúrgico. El resto de las lesiones mostraron una estabilidad (4 casos; 26%) e incluso un aumento de las dimensiones del tumor (10 casos; 66%) en el momento de la intervención. Cinco de los casos incluidos en este último grupo requirieron ingreso hospitalario en relación con la intervención quirúrgica. Conclusiones: El metotrexato intralesional como terapia neoadyuvante es una medida bien tolerada, que permite evitar cirugías agresivas en pacientes de edades avanzadas que presentan un queratoacantoma de diámetro superior a 1,5cm localizado en la región facial y acral (AU)

Background: Keratoacanthoma is currently considered to be an in situ squamous cell carcinoma that mainly affects patients over 70 years of age. The tumor has a good prognosis and, in some cases, can resolve spontaneously. Treatment involves simple excision. However, since the tumors generally occur on the face or extremities and display rapid growth, aggressive surgery may be required and the cosmetic results may be poor. Objective: The primary study objective was assessment of the efficacy of presurgical intralesional methotrexate infiltration to reduce the size of the tumor and the corresponding surgical defect. Material and methods: A prospective, randomized study was undertaken in patients with a diagnosis of keratoacanthoma of at least 1.5cm who were seen in our service between January 2009 and January 2010. Two groups were established: one receiving a single infiltration of methotrexate prior to surgery and another that did not receive methotrexate. Results: Of the 25 patients included in the study, 10 received neoadjuvant intralesional methotrexate (group A) and 15 underwent surgery without prior infiltration of methotrexate (group B). The patients in group A displayed a reduction of between 50% and 80% in the size of the lesion prior to surgery. No complications were observed either in relation to methotrexate infusion or surgery. In group B, only 1 patient had a slight reduction in the dimensions of the lesion prior to surgery. In the remaining cases, the lesions remained similar (4 cases, 26%) or had increased in size (10 cases, 66%) at the time of surgery. Five patients in this group required hospital admission following surgery. Conclusions: Neoadjuvant intralesional methotrexate is well tolerated and reduces the need for aggressive surgery in elderly patients with keratoacanthoma measuring more than 1.5cm on the face or extremities (AU)

[Massive pulmonary embolism treated with selective infusion of tenecteplase]. / Embolia polmonare massiva trattata con infusione selettiva di tenecteplase.

Massive pulmonary embolism (PE) is a cardiovascular emergency due to a substantial obstruction of the pulmonary vascular bed, resulting in rapid right heart failure with a potentially fatal outcome.We present the case of a 50-year-old woman with massive PE and recent trans-sphenoid surgery because of pituitary adenoma. An occluding embolus, arising from deep venous thrombosis of the lower limbs, was demonstrated in the right pulmonary artery with selective angiography and treated with selective loco-regional infusion of low-dose tenecteplase. To the best of our knowledge, this is the first case of selective administration of low-dose tenecteplase in the pulmonary artery with successful resolution of PE without the need for adjunctive interventional procedures.

Hearing evaluation of intratympanic methylprednisolone perfusion for refractory sudden sensorineural hearing loss.

OBJECTIVE: To investigate the effectiveness and safety of intratympanic methylprednisolone perfusion (IMP) through a microcatheter in patients with sudden sensorineural hearing loss (SSNHL) who failed a conventional treatment. STUDY DESIGN: Prospective clinical study. SETTING: This study was conducted in Nanjing Drum Tower Hospital, Nanjing University Medical School. SUBJECTS AND METHODS: Patients who had failed a minimum 10-day conventional treatment were included. Twenty-six patients in the study group (SG) received methylprednisolone perfusion through a microcatheter placed into the tympanum once a day for 10 days and the conventional treatment. Twenty-three patients who received a second conventional treatment (no steroid) served as the comparison group (CG). All patients were followed up for three months after the end of treatment. RESULTS: The effective rates for SG and CG were 50 percent (61.9% when only patients with an interval from onset to IMP < or = 60 days were included) and 21.7 percent, respectively (chi(2) = 4.194, P = 0.041). The pure-tone average improvement was 20.2 +/- 15.6 dB in SG, and 9.2 +/- 13.7 dB in CG (z = 2.51, P = 0.011). In SG, hearing improvement at low frequencies was better than that at high frequencies. The interval from onset to IMP affected the efficacy of IMP. CONCLUSION: IMP through a microcatheter is a promising treatment for refractory SSNHL. The data suggest that the treatment may be more effective when administered at the earlier stages of SSNHL when the conventional treatment has failed.

Experiencia en el tratamiento de satelitosis y metástasis cutáneas en tránsito de melanoma con interleucina 2 intralesional / Experience in the Treatment of Cutaneous In-Transit Melanoma Metastases and Satellitosis with Intralesional Interleukin-2

Introducción. A pesar del mal pronóstico del melanoma metastásico, las metástasis cutáneas constituyen un grupo especial por su fácil accesibilidad que lo hace susceptible al abordaje local por parte del dermatólogo. Describimos nuestra experiencia de tratamiento intralesional con interleucina 2 (IL-2) en 7 pacientes con metástasis cutáneas de melanoma maligno. Material y métodos. Un total de 244 lesiones en 7 pacientes con satelitosis y/o metástasis cutáneas de melanoma maligno han sido tratadas con IL-2 intralesional administrada dos veces a la semana. Las dosis máximas por pacientes variaron entre los 3 y 18 millones de unidades/sesión, en función del número y tamaño de las lesiones. Resultados. Se han obtenido remisiones completas (95,9 %) o parciales (3,7 %) en la gran mayoría de lesiones tratadas, una sola lesión (0,4 %), de localización subcutánea y de mayor tamaño, no respondió al tratamiento intralesional y precisó de alcoholización y posterior extirpación quirúrgica para su resolución. Todas las respuestas parciales se observaron en lesiones de localización subcutánea y mayores de 2 cm. El tratamiento fue bien tolerado, con escasos efectos secundarios de intensidad leve (grado 1-2). Conclusiones. La IL-2 puede ser una buena opción para el tratamiento de pacientes con satelitosis y metástasis cutáneas de melanoma con elevada eficacia y escasos efectos secundarios. Las lesiones menores de 2 cm y localizadas en epidermis o dermis superficial responden mejor que las mayores de 2 cm o localizadas en el tejido celular subcutáneo. Son necesarios más estudios para establecer las dosis y pautas de tratamiento adecuadas (AU)

Introduction. Although metastatic melanoma has a poor prognosis, cutaneous metastases represent a special case given their ready accessibility, making it possible for dermatologists to apply local treatment. We report our experience with intralesional treatment with interleukin (IL) 2 in 7 patients with cutaneous metastases from malignant melanoma. Material and methods. A total of 244 lesions in 7 patients with satellitosis and/or cutaneous metastases from malignant melanoma were treated with intralesional IL-2 twice a week. The maximum dose in each patient ranged from 3 to 18 million units per session, according to the number and size of lesions. Results. Complete or partial remission was achieved in almost all lesions (95.9 % and 3.7 %, respectively). Only 1 lesion (0.4 %)—the largest and located subcutaneously—did not respond to intralesional treatment and required alcoholization and subsequent surgical removal to achieve cure. All partial responses occurred in subcutaneous lesions larger than 2 cm. Treatment was well tolerated with only a few mild side effects (grade 1-2).Conclusions. IL-2 may be an effective and well-tolerated treatment option in patients with satellitosis and cutaneous metastases from melanoma. Lesions smaller than 2 cm and located in the epidermis or superficial dermis respond better than those larger than 2 cm or located in the subcutaneous cellular tissue. More studies are necessary to establish appropriate doses and regimens (AU)

Intraparenchymal and intratumoral interstitial infusion of anti-glioma monoclonal antibody 8H9.

OBJECTIVE: Interstitial infusion, a form of local delivery that bypasses the blood-brain barrier, has been shown to afford high regional concentrations of a therapeutic molecule while avoiding systemic exposure. The distribution of monoclonal antibodies administered via interstitial infusion has not been characterized, and this is salient in light of the potential sequestration by epitopes expressed by targeted tissue. Interstitial delivery of murine immunoglobulin G1 monoclonal antibody (MAb) 8H9 was investigated in a rodent model for the potential treatment of infiltrative gliomas. METHODS: MAb 8H9 was infused in varying concentrations and volumes into previously untreated animals and into an immunoreactive U87 xenograft to evaluate distributive potential. Previously untreated animals and athymic rats bearing U87 xenografts underwent variable infusions into the striatum or grafted tumor, respectively. Animals were sacrificed at multiple time points, and the volume of 8H9 distribution was determined using a new semiautomated technique. RESULTS: Increasing both the volume and dose of 8H9 infusion increased the volume of distribution. Distribution was significantly greater at 24 hours after infusion than at 1 hour. Interstitial infusion of MAb 8H9 resulted in a positive relationship between the volume of distribution and either the infusion volume or infusion dose. No significant difference in the volume of distribution was seen between antibodies in naïve striatum and U87 xenografts. Antibody distribution was effectively augmented by convection and diffusion after delivery. CONCLUSION: Finally, intratumoral interstitial infusion of a reactive MAb has been performed similarly to delivery to a normal brain. This finding is encouraging from a therapeutic standpoint, given the clinical need to affect large domains of these infiltrative tumors.