Mark G. Torchia

Results of the NeuroBlate System first-in-humans Phase I clinical trial for recurrent glioblastoma: clinical article.

OBJECT Laser interstitial thermal therapy has been used as an ablative treatment for glioma; however, its development was limited due to technical issues. The NeuroBlate System incorporates several technological advances to overcome these drawbacks. The authors report a Phase I, thermal dose-escalation trial assessing the safety and efficacy of NeuroBlate in recurrent glioblastoma multiforme (rGBM). METHODS Adults with suspected supratentorial rGBM of 15- to 40-mm dimension and a Karnofsky Performance Status score of ≥ 60 were eligible. After confirmatory biopsy, treatment was delivered using a rigid, gas-cooled, side-firing laser probe. Treatment was monitored using real-time MRI thermometry, and proprietary software providing predictive thermal damage feedback was used by the surgeon, along with control of probe rotation and depth, to tailor tissue coagulation. An external data safety monitoring board determined if toxicity at lower levels justified dose escalation. RESULTS Ten patients were treated at the Case Comprehensive Cancer Center (Cleveland Clinic and University Hospitals-Case Medical Center). Their average age was 55 years (range 34-69 years) and the median preoperative Karnofsky Performance Status score was 80 (range 70-90). The mean tumor volume was 6.8 ± 5 cm(3) (range 2.6-19 cm(3)), the percentage of tumor treated was 78% ± 12% (range 57%-90%), and the conformality index was 1.21 ± 0.33 (range 1.00-2.04). Treatment-related necrosis was evident on MRI studies at 24 and 48 hours. The median survival was 316 days (range 62-767 days). Three patients improved neurologically, 6 remained stable, and 1 worsened. Steroid-responsive treatment-related edema occurred in all patients but one. Three had Grade 3 adverse events at the highest dose. CONCLUSIONS NeuroBlate represents new technology for delivering laser interstitial thermal therapy, allowing controlled thermal ablation of deep hemispheric rGBM. CLINICAL TRIAL REGISTRATION NO.: NCT00747253 ( ClinicalTrials.gov ).

Dynamic MR lymphangiography and carbon dye for sentinel lymph node detection: A solution for sentinel lymph node biopsy in mucosal head and neck cancer†

The practical application of sentinel lymph node biopsy in squamous cell carcinoma of the head and neck is restricted by the time sensitivity of blue dye and lack of spatial resolution and nonspecific node enhancement with radiocolloid. This study evaluates the use of magnetic resonance (MR) lymphangiography and carbon dye labeling to circumvent these limitations.

The effect of vaginal prostaglandin E2 pessaries on induction of labor

In a prospective randomized study, patients with a valid obstetric indication for induction of labor received either 3 mg prostaglandin E2 vaginal pessaries immediately prior to oxytocin (prostaglandin group, n = 99), or oxytocin alone (oxytocin group, n = 103). At the conclusion of the second day of induction, a significant reduction was noted in the incidence of failed induction in the prostaglandin group (4%) as compared to the oxytocin group (13%) (p less than 0.05). Twenty percent of patients in the prostaglandin group experienced successful induction with prostaglandin pessaries only. When oxytocin was required in the prostaglandin group, the maximal concentration of oxytocin infused and the duration at this concentration were significantly less than in the oxytocin group. No perinatal complications were attributed to the use of prostaglandin. Three minor maternal complications that were attributed to vaginal prostaglandin E2 did not require treatment. Our conclusion is that patients who require an induction of labor, when artificial rupture of the membranes is not feasible, benefit from the use of prostaglandin pessaries before the administration of oxytocin.

Nitroglycerin Adsorption to Polyvinylchloride Seriously Interferes with Its Clinical Use

Extemporaneous preparations of intravenous nitroglycerin solutions are currently being used in a number of centers to control intraoperative hypertension (1), severe aortic regurgitation (2), and hypertension in pregnancy during cesarean section (3), and for reduction of myocardial ischemia (4). A satisfactory injectable product may be prepared by using sublingual nitroglycerin tablets (5), nitroglycerin adsorbed onto lactose (6), or directly synthesized nitroglycerin (7). The material is dissolved in normal saline and the solution is sterilized by filtration. With increasing use of intravenous nitroglycerin, a number of reports have been published describing apparent drug instability and binding to various intravenous containers and delivery sets. Several of these reports, however, provide conflicting data. Our center has used nitroglycerin intravenously for approximately 8 years and over this period it has been noted that often the response to the drug seemed to be inappropriate in relation to the dose administered. To determine the cause of this inconsistent dose response, a series of in vitro experiments has been performed in an effort to reproduce the findings of published reports and to relate these to our experiences with this drug. During the course of these investigations we were able to document a clinical case in which nitroglycerin was administered using two different delivery systems and thus compare our in vitro findings to an in vivo situation.

The C-terminal cytoplasmic domain of human proEGF is a negative modulator of body and organ weights in transgenic mice

We generated transgenic mice to study the in vivo role of the cytoplasmic domain of human proEGF (proEGFcyt). Post‐pubertal proEGFcyt transgenic (tg) mice displayed an up to 15% reduction in body weight, including smaller kidney and brain weights as compared to control littermates. Renal histology, gene expression profiles, and functional parameters were normal. In both sexes, serum levels of IGFBP‐3 were reduced. Circulating IGF‐I/IGF‐II levels were unchanged. Histomorphological analysis revealed isolated foci of liver necrosis specific to proEGFcyt tg mice. In conclusion, we identified proEGF cytoplasmic domain as a novel modulator of whole body and organ‐specific growth in mice.