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.

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.

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.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon / Craniofaringioma cístico: quimioterapia intratumoral com interferon alfa

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 percent and the bigger reduction was 98.37 percent. Eleven patients had a reduction greater than 90 percent. Five patients had a tumor reduction between 75 and 90 percent and in three patients the tumors were reduced by less than 75 percent. 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.

OBJETIVO: Avaliar se os craniofaringiomas císticos podem ser controlados com aplicações intratumorais de interferon alfa. MÉTODO: De janeiro de 2002 a abril de 2006, 19 pacientes foram submetidos à colocação de um cateter intracístico conectado a reservatório de Ommaya para aplicações intratumorais de ciclos de 36.000.000 de unidades de interferon alfa. A resposta ao tratamento foi avaliada pelo cálculo do volume tumoral na ressonância magnética de controle ao término de cada ciclo. RESULTADOS: Os pacientes receberam de um a quatro ciclos de quimioterapia. Onze pacientes apresentaram uma redução do volume tumoral maior que 90 por cento; cinco pacientes apresentaram uma redução entre 75 por cento e 90 por cento e três pacientes uma redução menor de 75 por cento. Não houve óbitos durante o tratamento e os efeitos colaterais do inferferon alfa foram bem tolerados. Nenhum tratamento foi interrompido. CONCLUSÃO: A quimioterapia intratumoral com interferon alfa diminui o volume dos craniofaringeomas císticos e pode ser considerada uma nova alternativa terapêutica.

Single-session percutaneous ethanol ablation of early-stage hepatocellular carcinoma with a multipronged injection needle: results of a pilot clinical study.

PURPOSE: To investigate the feasibility, safety, and efficacy of single-session ethanol ablation with multipronged needles in the treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A pilot clinical study enrolled 20 patients with Child-Pugh A-B cirrhosis (15 men and 5 women 53-84 years old [mean 70.3 years old ± 8.3, median 72 years old]) and with 25 HCC tumors 1.2-3.8 cm in longest diameter (mean 2.3 cm ± 0.6) located in unfavorable locations for radiofrequency (RF) ablation. Ethanol ablation was performed under moderate sedation using a multipronged injection needle (Quadra-Fuse; REX Medical, Conshohocken, Pennsylvania) and ultrasound guidance. Follow-up period ranged from 12-24 months (mean 15.9 months ± 4.6, median 16 months) and included contrast-enhanced computed tomography (CT) or magnetic resonance (MR) imaging performed 1 month after treatment and at 3-month intervals thereafter. RESULTS: The treatment protocol was successfully completed in all patients (technical success rate 100%). No major complications were observed. A single treatment session with injection of 5-26 mL of ethanol (mean 9.5 mL ± 5.5) resulted in complete tumor ablation at 1 month CT or MR imaging in 21 (84%) of 25 tumors. A second treatment session increased the number of tumors with complete response (CR) to 23 of 25 (primary effectiveness rate 92%). Tumor progression was observed in three cases during the follow-up period, for a rate of confirmed CR of 80% (20 of 25). CONCLUSIONS: Ethanol ablation performed with a multipronged injection needle was not associated with any major complications and resulted in a high rate of confirmed CR. This technique offers an alternative to RF ablation for single-session treatment of early-stage HCC.

Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers.

Stem cell-based therapy for patients with post-infarct heart failure is a relatively new and revolutionary concept in cardiology. Despite the encouraging results from pre-clinical studies, outcomes from most clinical trials remain moderately positive while the clinical benefits are largely attributed to transplanted cell-associated paracrine effects in stimulating angiogenesis and protecting endogenous cardiomyocytes. This scenario indicates that there may be a considerably protracted iterative process of conceptual and procedural refinement before true clinical benefits can be fully materialized. At present, many pressing questions regarding cell therapy remain unanswered. In addition to the primary interest in determining the ideal type of stem cells with best cardiogenic potential in vitro and in vivo, there are growing concerns on the impact of the host cardiac milieu on the transplanted cells, including their survival, migration, engraftment, and trans-differentiation as well as contribution to left ventricular function. Effective cell delivery and tracking methods are central to the unraveling of these questions. To date, cell-delivery modalities are yet to be optimized and strategies for safe and effective assessment of cells transplanted in the recipients are to be established. In this review, we discuss cell delivery and tracking modalities that are adopted in the current pre-clinical and clinical studies. We further discussed emerging technologies that are poised to impact the success of cell therapy.

Testing of neurosurgical needle steering via duty-cycled spinning in brain tissue in vitro.

A technique for steering of flexible bevel-tipped needles through tissue, providing proportional control of trajectory curvature by means of duty-cycled rotation or spinning during insertion, has been presented previously, and tested in vitro in gelatin samples. The present paper presents the results of testing under more authentic conditions. Thirty-two needle insertions were performed in cadaver brain tissue. Needle insertion was controlled interactively by the surgeon, adjusting parameters intraoperatively as needed based on fluoroscope images acquired at intervals of 1-2 cm of insertion depth. The average target acquisition error was 1.80 +/- 1.33 mm.

Ethanol ablation of hepatocellular carcinoma Up to 5.0 cm by using a multipronged injection needle with high-dose strategy.

PURPOSE: To investigate whether ethanol ablation by using a multipronged needle delivery system (multipronged ethanol ablation) could eradicate hepatocellular carcinoma (HCC) up to 5.0 cm in diameter with a single-session high-dose strategy. MATERIALS AND METHODS: The hospital ethics committee approved the prospective study, and each patient provided written informed consent. One hundred forty-one patients (125 men, 16 women; mean age, 53 years; range, 27-76 years) with 164 primary or recurrent HCC ranging from 1.3 to 5.0 cm in diameter (mean, 2.9 cm +/- 0.9) were treated with high-dose multipronged ethanol ablation. Patients were unsuitable for surgery, declined surgery and radiofrequency ablation, or had tumors located at unfavorable sites. Primary technique effectiveness (PTE) (complete ablation within two sessions), local tumor progression (LTP), and complications after the treatment were observed. Twenty risk factors of local effectiveness and complications were analyzed by means of univariate and multivariate analysis. RESULTS: Mean number of treatment sessions was 1.1. The mean volume of ethanol per tumor was 31 mL (range, 8-68 mL). PTE was achieved in 134 (95%) of 141 patients and was significantly associated with tumor pattern (capsulated vs noncapsulated, P = .018). After a mean follow-up period of 25 months, LTP was observed in 16 (12%) of 134 patients, and in nine (56%) patients, LTP occurred in tumors 3.1-5.0 cm in diameter. Alanine aminotransferase level (P = .023) was the independent risk factor for LTP. Three (2%) of 141 patients had major complications. CONCLUSION: Multipronged ethanol ablation with a high-dose strategy can be used to treat HCC up to 5.0 cm in diameter effectively and safely, often in a single session.