Fiberoptic Bronchoscopic Submucosal Injection of Mitomycin C for Recurrent Bening Tracheal Stenosis: A Case Series.

BACKGROUND: Benign tracheal stenosis has emerged as a therapeutic challenge for physicians involved in the care of survivors of critical care units. Although the traditional mainstay of open surgical reconstructive treatment is still considered the gold standard, endoscopic therapies such as laser re-canalization, balloon dilation, or stenting are commonly practiced in invasive bronchology. Recurrent obstructing granulomas pose a challenge for bronchoscopists. Mitomycin C (MyC) is a cytotoxic agent that is isolated from Streptomyces caespitosus and acts by inhibiting DNA and RNA synthesis through alkylation and cross-linkages. Topical MyC is commonly used in indirect laryngoscopies for the treatment of granulation tissue in the trachea by using saturated pledgets. OBJECTIVES: To describe fiberoptic bronchoscopic submucosal injection of MyC as a treatment for recurrent bening tracheal stenosis. METHODS: The authors report their successful experience with submucosal intralesional injection of MyC in the management of recurrent obstructing granulomas/stenosis using the flexible fiberoptic bronchoscope in a series of 10 patients between 2005 and 2019. RESULTS: The results suggest that intralesional injection of MyC using the flexible bronchoscope after the endoscopic treatment of the stenotic lesion may reduce the rate of subsequent formation of granulation tissue and scarring without side effects. CONCLUSIONS: The efficacy of MyC injection should be studied prospectively.

Phase I trial of intracerebral convection-enhanced delivery of carboplatin for treatment of recurrent high-grade gliomas.

BACKGROUND: Carboplatin is a potent cytoreductive agent for a variety of solid tumors. However, when delivered systemically, clinical efficacy for the treatment of high grade gliomas is poor due to limited penetration across the blood-brain barrier (BBB). Direct intracerebral (IC) convection-enhanced delivery (CED) of carboplatin has been used to bypass the BBB and successfully treat the F98 rat glioma. Based on these studies, we initiated a Phase I clinical trial. OBJECTIVE: This Phase I clinical trial was conducted to establish the maximum tolerated dose and define the toxicity profile of carboplatin delivered intracerebrally via convection enhanced delivery (CED) for patients with high grade glial neoplasms. METHODS: Cohorts of 3 patients with recurrent WHO grade III or IV gliomas were treated with escalating doses of CED carboplatin (1-4 µg in 54mL over 72 hours) delivered via catheters placed at the time of recurrent tumor resection. The primary outcome measure was determination of the maximum tolerated dose (MTD). Secondary outcome measures included overall survival (OS), progression-free survival (PFS), and radiographic correlation. RESULTS: A total of 10 patients have completed treatment with infusion doses of carboplatin of 1µg, 2µg, and 4µg. The total planned volume of infusion was 54mL for each patient. All patients had previously received surgery and chemoradiation. Histology at treatment include GBM (n = 9) and anaplastic oligodendroglioma (n = 1). Median KPS was 90 (range, 70 to 100) at time of treatment. Median PFS and OS were 2.1 and 9.6 months after completion of CED, respectively. A single adverse event possibly related to treatment was noted (generalized seizure). CONCLUSIONS: IC CED of carboplatin as a potential therapy for recurrent malignant glioma is feasible and safe at doses up to 4µg in 54mL over 72 hours. Further studies are needed to determine the maximum tolerated dose and potential efficacy.

[Laryngeal dystonia: novel forms of therapeutic administration of botulinum toxin by direct routes]. / Distonia laringea: nuevas formas de administracion terapeutica de toxina botulinica por via directa.

AIM: To describe our experience in the treatment of laryngeal dystonia (in abduction and adduction), with special emphasis given to the technical aspects (approach procedure, dosage and type of botulinum toxin type A used), as well as treatment response and possible side effects. PATIENTS AND METHODS: We conducted a cross-sectional descriptive study of a sample of patients with laryngeal dystonia treated by means of transoral administration of onabotulinumtoxinA or incobotulinumtoxinA over a period of 10 years (2007-2017). Data collected include demographic and clinical variables, treatment response (based on a self-rating scale), the duration of treatment and the appearance of side effects. SAMPLE SIZE: 15 patients (11 women; mean age: 44.06 years) with laryngeal dystonia (mean time since onset of 40 months; 12 patients with dystonia in adduction) and 174 administrations (92% incobotulinumtoxinA; average dosage of 5 U in each vocal cord). The procedure took an average of 11.7 minutes to perform. Response was good in 31% of the procedures and very good in 57.5%. Side effects were recorded in 14.4% of the procedures, although always mild and transitory, with a predominance of dysphagia and dysphonia. CONCLUSION: In our experience, transoral administration of botulinum toxin type A to treat laryngeal dystonia has proved to be a simple, quick, effective and safe technique.

TITLE: Distonia laringea: nuevas formas de administracion terapeutica de toxina botulinica por via directa.Objetivo. Describir nuestra experiencia en el tratamiento de la distonia laringea (en abduccion y aduccion), destacando los aspectos tecnicos (procedimiento de abordaje, dosis y tipo de toxina botulinica de tipo A utilizada), asi como la respuesta al tratamiento y los posibles efectos adversos. Pacientes y metodos. Estudio descriptivo transversal de una muestra de pacientes con distonia laringea tratados mediante administracion transoral de onabotulinumtoxina o incobotulinumtoxina A durante un periodo de 10 años (2007-2017). Se recogen las variables demograficas y clinicas, la respuesta al tratamiento (a partir de una escala de autoevaluacion), la duracion de este y la aparicion de efectos adversos. Resultados. Tamaño muestral: 15 pacientes (11 mujeres; edad media: 44,06 años) con distonia laringea (tiempo medio de evolucion de 40 meses; 12 pacientes con distonia en aduccion) y 174 administraciones (92% incobotulinumtoxina A; dosis media de 5 U en cada cuerda vocal). La duracion media del procedimiento fue de 11,7 minutos. La respuesta fue notable en el 31% de los procedimientos y alta en el 57,5%. Se registraron efectos adversos en el 14,4% de los procedimientos, siempre de caracter leve y transitorio, con predominio de la disfagia y la disfonia. Conclusion. En nuestra experiencia, la administracion transoral de toxina botulinica de tipo A como tratamiento de la distonia laringea ha demostrado ser una tecnica sencilla, rapida, eficaz y segura.

US-guided percutaneous release of the first extensor tendon compartment using a 21-gauge needle in de Quervain's disease: a prospective study of 35 cases.

PURPOSE: To evaluate the efficacy of ultrasonography-guided percutaneous treatment of de Quervain tenosynovitis with the combination of a corticosteroid injection and release of the retinaculum of the first extensor compartment tendons with a 21-gauge needle. MATERIALS AND METHODS: The first part of our study consisted of ten procedures on cadaver wrists followed by dissection to analyse the effectiveness of the retinaculum release and detect any collateral damage. The second part was a prospective clinical study of 35 procedures. Outcomes were evaluated through a 6-month clinical follow-up and telephone interview at the end of the study. The following parameters were monitored over time: pain level on a visual analogue scale, the QuickDASH and the PRWE. Patient satisfaction questionnaires were also administered. RESULTS: No complications were found during the cadaver study. However, the release was confirmed as 'partial' in all wrists. In the clinical portion of this study, significant improvement was observed in 91.4 % of cases (32/35) within 1 month and the results were stable until the end of the study; all of these patients avoided surgery. The release procedure failed in three patients who eventually required surgical treatment. CONCLUSION: US-guided partial release and simultaneous corticosteroid injection for treatment of de Quervain's disease using a 21-gauge needle is feasible in current practice, with minimal complications. KEY POINTS: • Ultrasound-guided treatment of de Quervain's disease is feasible with a 21G needle. • There was notable regression of clinical signs in 91.4 % of cases. • The procedure is very safe, no iatrogenic neurovascular or tendinous injuries occurred. • Our procedure requires only one session and 3 days away from work.

Pharmacokinetics and safety of paclitaxel delivery into porcine airway walls by a new endobronchial drug delivery catheter.

BACKGROUND AND OBJECTIVE: Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side-effect profiles are poorly understood. METHODS: Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28 days post-injection. RESULTS: Injection of generic PTX directly into the bronchial wall at doses up to 1.5 mg/mL only caused minimal tissue injury. Dose-limiting tissue reaction was observed at 2.5 mg/mL. Plasma PTX was detectable for up to 5 days but not at 28 days, with area under the curve (AUC)(0-5d) 20- to 50-fold lower than the AUC(0-∞) of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days post-injection, bronchial PTX tissue concentrations were above a 10-nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX. CONCLUSION: Results of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7 days but tissue concentrations remained therapeutic throughout the follow-up period.

A Hand-Held Assistant for Semiautomated Percutaneous Needle Steering.

OBJECTIVE: Permanent prostate brachytherapy is an effective and popular treatment modality for prostate cancer in which long needles are inserted into the prostate. Challenges associated with manual needle insertion such as needle deflection limit this procedure to primarily treat the entire prostate gland even for patients with localized cancer. In this paper, we present a new semiautomated hand-held needle steering assistant designed to help surgeons improve needle placement accuracy. METHODS: Regular clinical brachytherapy needles are connected to a compact device that the surgeon holds. As the surgeon inserts the needle, the device rotates the needle base on a measured and calculated basis in order to produce a desired trajectory of the needle tip. A novel needle-tissue interaction model and a steering algorithm calculate such control actions based on ultrasound images of the needle in tissue. The assistant can also apply controlled longitudinal microvibrations to the needle that reduce needle-tissue friction. RESULTS: Experimental validation of the proposed system in phantom and ex-vivo biological tissue report an average needle targeting accuracy of 0.33 mm over 72 needle insertions in 12 different experimental scenarios. CONCLUSION: We introduce a new framework for needle steering in prostate brachytherapy in which the surgeon remains in charge of the needle insertion. The device weighs 160 g, making it easy to incorporate with current insertion techniques. SIGNIFICANCE: Expected benefits of the proposed system include more precise needle targeting accuracy, which can result in improved focal treatment of prostate cancer.

Calcifilaxis tratada con tiosulfato sódico intralesional / Intralesional Sodium Thiosulfate to Treat Calciphylaxis

No disponible

Development of the Biopen: a handheld device for surgical printing of adipose stem cells at a chondral wound site.

We present a new approach which aims to translate freeform biofabrication into the surgical field, while staying true to the practical constraints of the operating theatre. Herein we describe the development of a handheld biofabrication tool, dubbed the 'biopen', which enables the deposition of living cells and biomaterials in a manual, direct-write fashion. A gelatin-methacrylamide/hyaluronic acid-methacrylate (GelMa/HAMa) hydrogel was printed and UV crosslinked during the deposition process to generate surgically sculpted 3D structures. Custom titanium nozzles were fabricated to allow printing of multiple ink formulations in a collinear (side-by-side) geometry. Independently applied extrusion pressure for both chambers allows for geometric control of the printed structure and for the creation of compositional gradients. In vitro experiments demonstrated that human adipose stem cells maintain high viability (>97%) one week after biopen printing in GelMa/HAMa hydrogels. The biopen described in this study paves the way for the use of 3D bioprinting during the surgical process. The ability to directly control the deposition of regenerative scaffolds with or without the presence of live cells during the surgical process presents an exciting advance not only in the fields of cartilage and bone regeneration but also in other fields where tissue regeneration and replacement are critical.

Drug coated microneedles for minimally-invasive treatment of oral carcinomas: development and in vitro evaluation.

Treatment of recurring oral cancers is challenging as common surgical approaches are not feasible for these patients. In addition, these patients do not respond well to systemic chemotherapy. Localized intratumoral injection of anti-cancer drugs is considered to be an attractive alternative treatment approach for these patients. However, conventional hypodermic injections result in poor distribution of the drug in the tumor and leakage of the drug from the injection site to systemic circulation, in addition to causing pain to the patient. The objective of this study was to develop coated microneedles as a novel device for direct and minimally invasive intratumoral delivery of anti-cancer drugs. Poly(lactic-co-glycolic) acid (PLGA) nanoparticles encapsulating doxorubicin (DOX) were prepared and coated on inplane (1D) microneedles. Microscopic evaluation of 3D tissue phantoms and porcine cadaver buccal tissues that were treated with 1D microneedle arrays coated with DOX-PLGA nanoparticles demonstrated that DOX could diffuse both laterally and vertically in to the tissues and produced cellular cytotoxicity. Out of plane (2D) microneedle arrays measuring 1 cm x 1 cm with 57 microneedles coated with free DOX could produce uniform distribution of DOX in a porcine cadaver buccal tissue up to a depth greater than 3 mm. Hypodermic injection of different volumes in to a porcine buccal tissue confirmed significant leakage of the injected volume (about 25% of the injected 80 µl). In summary, this study demonstrates that drug coated microneedles is an attractive microscale device that can uniformly and effectively deliver drugs to localized oral cancers. This microscale device has potential to impact the treatment of oral cancer patients.

Combined radiofrequency ablation and ethanol injection with a multipronged needle for the treatment of medium and large hepatocellular carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of combined radiofrequency ablation (RFA) and ethanol injection with a multipronged needle in the treatment of medium (3.1-5.0 cm) and large (5.1-7.0 cm) hepatocellular carcinoma (HCC). METHODS: A total of 65 patients with 67 HCC nodules were enrolled in this prospective study. All of them received the treatment of combined RFA and multipronged ethanol injection percutaneously. RESULTS: The average volume of injected ethanol was 14.4 ± 4.1 ml (range, 9-30 ml). The average number of RFA electrode insertions was 1.7 ± 0.8 (range, 1-4). The rate of initial local complete response (CR) was 94.0 % (63/67). After additional treatment, technical success was achieved in all HCC nodules. There were no treatment-related deaths, and major complications were observed in 3 (4.6%) patients. After a mean follow-up of 20.0 ± 7.6 months, local tumour progression was observed in 10 (10/67, 14.9%) tumours, whereas distant recurrence developed in 32 (32/65, 49.2%) patients. The 1-year and 2-year survival rates were 93.1% and 88.1%, respectively. CONCLUSION: The combination of RFA and multipronged ethanol injection in the treatment of medium and large HCC is safe and effective with a high rate of local tumour control. KEY POINTS: • Combined radiofrequency ablation and multipronged ethanol injection is a new therapeutic strategy • Treatment is safe and effective for medium and large hepatocellular carcinoma (HCC) • A multipronged needle allows for a homogeneous ethanol distribution.

[Skin needle roller importing triamcinolone acetonide into scar to treat hypertrophic scars].

OBJECTIVE: To evaluate the effect of importing triamcinolone acetonide into hypertrophic scars with skin roller needles. METHODS: Thirty-two cases with burn hypertrophic scar were treated. The skin roller needles were moved back and forth on the hypertrophic scars with triamcinolone acetonide dropping on the scar surface at the same time. So the triamcinolone acetonide could be imported into the scar through needles and needle holes. The effect was evaluated as cured, effective, and no effect. The Vancouver scaring criteria and visual analogue scale was used to assess the scar color, thickness, texture and feeling before and after treatment, as well as at the untreated scar area (control). RESULTS: Thirty-two cases were treated 1-3 times, including 28 cases with cured result and 4 cases with effective result. The total effective rate was 100%. The scar color, thickness, texture and feeling was significantly different between the scar before and after treatment, or between the treated and untreated scar (P < 0.05). CONCLUSIONS: Importing triamcinolone acetonide into hypertrophic scars with skin roller needles is effective. It is a new method for the treatment of large hypertrophic scar with medicine.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon.

OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

Novel method of intralesional cidofovir injection into laryngotracheal papillomata.

Laryngeal papillomatosis is characterised by multiple papillomata affecting the upper respiratory tract. This condition is difficult to treat due to its recurrent nature. Treatment often involves surgical debulking. A number of non-surgical treatments have been reported. Intralesional cidofovir, a cytosine nucleoside analogue with antiviral activity, has been used in an attempt to manage the condition. We present a novel technique of administering cidofovir in a case of recurrent laryngotracheal papillomata.