A pilot study in intraparenchymal therapy delivery in the prostate: a comparison of delivery with a porous needle vs standard needle.

BACKGROUND: New biologic therapies directly injected into the prostate are in clinical trials for prostatic diseases. There is a need to understand distribution of injected therapies as a function of prostatic anatomy, physiology, and device design. METHODS: A needle with a porous length of customizable-length was tested and its performance compared with a standard needle. Injections of magnetic resonance contrast reagent were placed into ex-vivo human prostates after surgical excision in standard of care therapy for invasive bladder cancer patients. Magnetic resonance images were acquired using sequences to quantify volume delivered, distributed, and backflow. RESULTS: Magnetic resonance images analysis revealed heterogeneity distribution with injection into the specimens. There was low resistance to flow along ductal pathways and high resistance to flow into glandular nodules and smooth muscle/fibrous parenchyma. Data confirm previous studies showing injection loss via urethra backflow, urethra, and prostatic ducts. Tissue fraction of dose was significantly higher with porous needle compared with standard needle (p = .03). We found that a greater volume of distribution divided by the amount infused (Vd/Vi) increased by 80% with the porous needle, though no statistically significant association due to small sample size. CONCLUSIONS: This study demonstrated that prostatic tissue is anatomically heterogenic and limits distribution of needle injection. There is greater distribution in the ex-vivo prostate using a porous needle. The complexity of intra prostatic flow pathways suggests preoperative imaging and pre-treatment planning will enhance therapy.

Large-Volume Infusions into the Brain: A Comparative Study of Catheter Designs.

BACKGROUND/AIMS: "Whole-brain" infusions have emerged as a potential need with the promise of disease-modifying therapies for neurodegenerative diseases. In addition, several current clinical trials in brain cancer utilize direct delivery of drugs that are required to fill large volumes. Such requirements may not be well served by conventional single port catheters with their "point source" of delivery. Our aim is to examine infusions into large volumes of heterogeneous tissue, aiming for uniformity of distribution. METHODS: A porous catheter (porous brain infusion catheter, PBIC), designed by Twin Star TDS LLC, for brain infusions was developed for this study and compared with another convection-enhanced delivery catheter (SmartFlowTM NGS-NC-03 from MRI Interventions, a step end-port catheter, SEPC) in current use in clinical trials. The studies were in vivo in porcine brain. A total of 8 pigs were used: the size of the pig brain limited the porous length to 15 mm. The placements of the tips of the two catheters were chosen to be the same (at the respective brain hemispheres). RESULTS: The PBIC and SEPC both performed comparably and well, with the PBIC having some advantage in effecting larger distributions: p ∼ 0.045, with 5 infusions from each. CONCLUSIONS: Given the performance of the PBIC, it would be highly appropriate to use the device for therapeutic infusions in human clinical trials to assess its capability for large-volume infusions.

Comparison of intraprostatic ethanol diffusion using a microporous hollow fiber catheter versus a standard needle.

PURPOSE: Transurethral intraprostatic ethanol chemoablation of the prostate has shown promising preliminary clinical results for benign prostatic hyperplasia with some variability in clinical outcome. This is likely due to the uneven prostate diffusion caused by varying resistance of the tissue type in which the tip of the needle is embedded. We examined whether the distribution of the injectable in the canine prostate could be improved using a microporous hollow fiber catheter (Twin Star Medical, Minneapolis, Minnesota). MATERIALS AND METHODS: The prostate was exposed in 9 mongrel dogs. A single injection of 98% ethanol was delivered in each lobe using a microporous hollow fiber catheter and a standard needle. Prostates were harvested and fixed in 10% formalin. After injection 2.5 mm step sections were obtained and scanned. The ethanol induced tissue lesions were traced on hematoxylin and eosin sections. Three-dimensional reconstructions were created and the volume of each prostate lesion was calculated using stereology. RESULTS: Ethanol induced tissue changes were seen bilaterally in 8 of 9 ethanol injected prostates. In all cases the lesion created by microporous hollow fiber catheter injection was larger than that in the contralateral lobe injected with the control needle. When data were pooled, the hollow fiber catheter injection produced significantly greater tissue changes than the control needle injection (p = 0.03). CONCLUSIONS: Improved distribution and absent backflow were seen when using the microporous hollow fiber catheter, supporting its potential as a new method to treat prostate disease.

Hypertonic saline reduces intracranial hypertension in the presence of high serum and cerebrospinal fluid osmolalities.

BACKGROUND: Osmotherapy has been the cornerstone in the management of patients with elevated intracranial pressure (ICP) following traumatic brain injury (TBI). Several studies have demonstrated that hypertonic saline (HTS) is a safe and effective osmotherapy agent. This study evaluated the effectiveness of HTS in reducing intracranial hypertension in the presence of a wide range of serum and cerebrospinal fluid (CSF) osmolalities. METHODS: Forty-two doses of 23.4% saline boluses for treatment of refractory intracranial hypertension were reviewed retrospectively. Thirty milliliters of 23.4% NaCl was infused over 15 min for intracranial hypertension, defined as ICP >20 mmHg. The CSF and serum osmolalities from frozen stored samples were measured with an osmometer. The values of serum sodium, hourly ICP, blood urea nitrogen (BUN), and creatinine were obtained directly from the medical records. RESULTS: The serum and CSF osmolalities correlated very closely to serum sodium (r > 0.9, P < 0.0001). The reduction in ICP from the baseline (measured from either the mean ICP or the lowest ICP measurement in the first 6 h after bolus HTS treatment) was statistically significant regardless of serum osmolality. The mean reduction from baseline to follow-up values was 8.8 mm Hg (P < 0.0001). The decrease in ICP was as evident with serum osmolalities >320 as it was at ≤320. CONCLUSION: This study demonstrates that 23.4% HTS bolus is effective for the reduction of elevated ICP in patients with severe TBI even in the presence of high serum and CSF osmolalities.

Threshold model for extremity compartment syndrome in swine.

BACKGROUND: Extremity compartment syndrome occurs when swelling develops within a muscle compartment to such an extent that the microvasculature is compressed and tissue perfusion is compromised. Untreated, this condition can result in widespread tissue destruction and loss of the affected limb. METHODS: Swine were subjected to diffuse muscle compression injury using a balloon catheter inserted between the anterior muscle compartment of the hind limb and the anterior face of the tibia. Balloons were inflated with saline to produce a sustained intramuscular pressure (IMP) of approximately 30 mmHg greater than mean arterial pressure. Following injury the IMP was monitored for up to 8 h. At the end of the monitoring period, the tibialis anterior muscle was collected and examined for injury. RESULTS: One animal receiving 6 h injury dislodged the implanted pressure transducers and was dropped from the data analysis. In all other limbs (n = 8) receiving 6 h injury, significant spontaneous increases in IMP were observed following injury. The tibialis anterior in all of the 6 h injury limbs also showed extensive tissue damage. In the limbs injured for 5 h (n = 10), only three showed a significant increase in IMP. The magnitude and duration of this increase closely resembled that seen following 6 h injury. Tissue damage was reduced in comparison with 6 h injury. CONCLUSIONS: The injury technique described here provides a potential useful threshold model for studying extremity compartment syndrome and the influence of related factors on the progression of this condition.

Severe nasal frostbite injury from nasal cannula supplemental oxygen malfunction.

We describe the presentation and management of a patient who presented to our institution with severe nasal frostbite from nasal cannula supplemental oxygen malfunction. This rare complication has not previously been reported in the English Literature. We describe the physical properties of compressed oxygen release that may contribute to these malfunctions and the role of the otolaryngologist in the management of the resulting injuries.

Extremity compartment syndrome in pigs during hypobaric simulation of aeromedical evacuation.

INTRODUCTION: Extremity compartment syndrome (ECS) is diagnosed when the pressure within a muscle compartment increases to within 45 mmHg of mean arterial pressure. Increased pressure limits perfusion and eventually produces tissue necrosis. This can result in disability or loss of the affected limb. Hypobaric pressure during aeromedical evacuation (AE) has been hypothesized to increase the incidence of ECS. This was tested in a threshold model of ECS in swine. METHODS: Injury was induced by placing an angioplasty balloon between the tibia and the anterior muscle compartment and inflating the balloon to produce an intracompartmental pressure (ICP) 30 mmHg greater than mean arterial pressure for either 5 h or 6 h. Afterwards, animals were maintained either at ground level pressure or at a pressure equivalent to a simulated altitude of 2135 m above sea level for 8 h. ICP was monitored for signs of ECS development. At the end of the period the muscle was collected and evaluated for pathological changes and expression of various molecules associated with inflammation and tissue injury. RESULTS: Simulated altitude did not increase incidence of ECS, peak intracompartmental pressures, or time to onset of ECS. However, muscle degeneration and formation of microvascular thrombi were reduced by exposure to altitude. TNF, IL-1 b, IL-6, IGFBP5, and TGFB2 were increased (P < 0.05) by exposure to altitude, whereas FGF, IGF1, IGFBP4, BMP4, nitrotyrosine, and nitrate were unchanged (P > 0.05). DISCUSSION: Simulated altitude did not increase incidence of ECS. Inflammatory protein expression was increased in muscle, but some aspects of pathology were less severe following altitude exposure.

Novel In Situ Collection of Tumor Interstitial Fluid from a Head and Neck Squamous Carcinoma Reveals a Unique Proteome with Diagnostic Potential.

INTRODUCTION: Tumors lack normal drainage of secreted fluids and consequently build up tumor interstitial fluid (TIF). Unlike other bodily fluids, TIF likely contains a high proportion of tumor-specific proteins with potential as biomarkers. METHODS: Here, we evaluated a novel technique using a unique ultrafiltration catheter for in situ collection of TIF and used it to generate the first catalog of TIF proteins from a head and neck squamous cell carcinoma (HNSCC). To maximize proteomic coverage, TIF was immunodepleted for high abundance proteins and digested with trypsin, and peptides were fractionated in three dimensions prior to mass spectrometry. RESULTS: We identified 525 proteins with high confidence. The HNSCC TIF proteome was distinct compared to proteomes of other bodily fluids. It contained a relatively high proportion of proteins annotated by Gene Ontology as "extracellular" compared to other secreted fluid and cellular proteomes, indicating minimal cell lysis from our in situ collection technique. Several proteins identified are putative biomarkers of HNSCC, supporting our catalog's value as a source of potential biomarkers. CONCLUSIONS: In all, we demonstrate a reliable new technique for in situ TIF collection and provide the first HNSCC TIF protein catalog with value as a guide for others seeking to develop tumor biomarkers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12014-010-9050-3) contains supplementary material, which is available to authorized users.

Surgical debridement and adjunctive hyperbaric oxygen in cervical necrotizing fasciitis.

OBJECTIVE: To review our management of cervical necrotizing fasciitis (CNF) with the use of adjunctive hyperbaric oxygen therapy (HBO). STUDY DESIGN: Case series with chart review. SUBJECTS AND METHODS: Evaluation of ten patients with CNF between 2001 to 2006. RESULTS: There were five male and six female patients. Mean age was 43 +/- 11 years. Eight cases resulted from an odontogenic source. Comorbidities included diabetes mellitus, hypertension, and substance abuse. All patients had computed tomography scans performed, received intravenous antibiotics, and underwent surgical debridement. Eight patients underwent surgery within 24 hours. The average number of debridements was 2.2 +/- 0.8. Hospitalization was twice as long for diabetic patients (15.5 +/- 8.16 days) compared with nondiabetic patients (7.5 +/- 1.6 days, P = 0.029). Nine patients had HBO therapy. Combined data revealed a possible decrease in length of hospitalization with HBO therapy (P < 0.001). No mortality was documented. CONCLUSION: In addition to early and aggressive medical management and surgical debridement, this study suggests that HBO therapy is a beneficial adjunct by potentially decreasing length of hospitalization. Randomized trials are still needed to demonstrate its efficacy.

Diagnosis and treatment of deep neck space abscesses.

OBJECTIVE: To review our experience with deep neck abscesses and identify unique trends in our patient population. STUDY DESIGN: Case series with chart review. SUBJECTS AND METHODS: Evaluation of patients with deep neck space abscesses between 2001 and 2006. Peritonsillar abscess, superficial craniocervical infection, and salivary gland infections were excluded from selection of study population. A total of 106 cases were reviewed. RESULTS: Dental infections were the most common cause of deep neck abscesses (49.1%). Comorbidities included substance abuse (53.7%), psychiatric illness (10.4%), hypertension (9.4%), head and neck cancer (6.6%), and diabetes mellitus (5.7%). All patients received systemic antibiotics, eight patients required tracheotomy, 85 patients underwent surgical drainage in the operating room, and 11 had bedside drainage. Median and lower quartile of time in hospital was 2 and 3 days, respectively, whereas upper quartile was 4 days (range, 1 to 27 days). Patients with comorbidities or concurrent illness tended to stay longer (P<0.05, Mann-Whitney test). There were six complications and no mortality. CONCLUSION: Substance abuse and poor orodental hygiene are important predisposing factors to deep neck abscesses. Appropriate management continues to favor a combination of early surgical drainage and systemic antibiotics.

Analysis of results in early versus late midface fracture repair.

OBJECTIVE: To evaluate the complication rate in relation to the timing of surgical repair of midface fractures. STUDY DESIGN AND SUBJECTS: Retrospective chart review at a level 1 trauma center. RESULTS: Thirty-four patients were evaluated. Overall complication rate was 23.5% with no significant difference between the early repair (21.1%) and late repair (26.7%) groups. The scope of facial fracture repair was similar between the two groups as measured by the number of screws used and through an injury quantifying system. The only variable that tended toward significance was intraoperative blood loss, which was greater in the early repair group (P = 0.06). CONCLUSIONS: There is no clear consensus with respect to timing of midface trauma repair. Early repair may result in greater blood loss. Further study is needed to help establish a more precise recommendation for the timing of midface trauma repair.

Improved distribution of small molecules and viral vectors in the murine brain using a hollow fiber catheter.

OBJECT: A hollow fiber catheter was developed to improve the distribution of drugs administered via direct infusion into the central nervous system (CNS). It is a porous catheter that significantly increases the surface area of brain tissue into which a drug is infused. METHODS: Dye was infused into the mouse brain through convection-enhanced delivery (CED) using a 28-gauge needle compared with a 3-mm-long hollow fiber catheter. To determine whether a hollow fiber catheter could increase the distribution of gene therapy vectors, a recombinant adenovirus expressing the firefly luciferase reporter was injected into the mouse striatum. Gene expression was monitored using in vivo bioluminescent imaging. To assess the distribution of gene transfer, an adenovirus expressing green fluorescent protein was injected into the striatum using a hollow fiber catheter or a needle. RESULTS: Hollow fiber catheter-mediated infusion increased the volume of brain tissue labeled with dye by 2.7 times relative to needle-mediated infusion. In vivo imaging revealed that catheter-mediated infusion of adenovirus resulted in gene expression that was 10-times greater than that mediated by a needle. The catheter appreciably increased the area of brain transduced with adenovirus relative to a needle, affecting a significant portion of the injected hemisphere. CONCLUSIONS: The miniature hollow fiber catheter used in this study significantly increased the distribution of dye and adenoviral-mediated gene transfer in the mouse brain compared with the levels reached using a 28-gauge needle. Compared with standard single-port clinical catheters, the hollow fiber catheter has the advantage of millions of nanoscale pores to increase surface area and bulk flow in the CNS. Extending the scale of the hollow fiber catheter for the large mammalian brain shows promise in increasing the distribution and efficacy of gene therapy and drug therapy using CED.

Paranasal sinus osteomas and Gardner's syndrome.

OBJECTIVES: Osteomas are common benign tumors of the paranasal sinuses. The origin of these lesions is uncertain. Although most are asymptomatic, symptoms can include headaches, facial pain, rhinorrhea, and sinusitis. Osteomas are also seen as part of Gardner's syndrome, an autosomal dominant disease characterized by intestinal polyposis, osteomas, and cutaneous and soft tissue tumors. In affected individuals, the risk of developing colon cancer approaches 100%. On average, osteomas are detected 17 years before colon polyps appear. METHODS: Three patients with maxillary or ethmoid osteomas and chronic sinusitis are presented. RESULTS: One of the patients had evidence of Gardner's syndrome, based on the presence of gastrointestinal symptoms and a positive family history of polyposis. CONCLUSIONS: Otolaryngologists should be aware of the possibility of Gardner's syndrome in patients with paranasal sinus osteomas. Suspected patients should have a complete workup for Gardner's syndrome, including lower gastrointestinal tract endoscopy, barium enema imaging, and DNA testing.

Theory of porous catheters and their applications in intraparenchymal infusions.

Multiport catheters and catheters with a porous surface have been proposed for intraparenchymal infusions of therapeutics in fluid suspensions. Target diseases include brain cancer and serious neurodegenerative diseases, as well as peripheral tumors, for example in the prostate and the liver. We set up the theory for infusions from such devices, in particular the fluid flow equations which demand a coupling between the flow within the catheter and that in tissue. (Such a coupling is not necessary in the theory of infusion from single port catheters.) The new feature of such catheters, treated by our model, is revealed by infusions into inhomogeneous media. Multiport designs have the potential to overcome the limitation of single port catheters, for which the path of the fluid leaving the port is dominated by the inhomogeneities. We solve these equations for some simple cases to illustrate the key design features of porous catheters that show such advantages. The mathematics required for numerical solution with more realistic assumptions is also developed. We confirm the robustness of such catheters, when the ports are sufficiently resistive, against leakage paths that would compromise the infusions from catheters with one or a few large ports. The methods of this paper can be incorporated into a larger planning system for intraparenchymal infusions involving such devices.

Computed tomography scan does not correlate with patient experience of nasal obstruction.

OBJECTIVES/HYPOTHESIS: Third-party payors have begun to demand imaging studies to document septal deviation prior to authorizing septoplasties. This study aims to determine whether septal deviation findings on computed tomography (CT) correlate with symptoms of nasal obstruction as determined by the Nasal Obstruction Symptom Evaluation (NOSE) scale. STUDY DESIGN: Prospective and retrospective chart review. METHODS: Patients 18 years or older undergoing CT scans, which included the nasal septum, were asked to complete a NOSE scale survey and report the laterality of any possible obstruction. Coronal CT images of subjects were graded by two blinded otolaryngologists and two blinded neuroradiologists using a grading system devised by the authors. RESULTS: Seventy-three subjects met inclusion/exclusion criteria. Interobserver reliability about the degree of septal deviation on CT scans was moderately good to substantial (κ values, 0.43 to 0.72). There was poor correlation between NOSE scores and degree of deviation on CT scans (Kendall's τ, 0.031 to 0.045; P values all >.05). There was poor concordance between the side of symptoms that patients reported and the side that observers thought was most deviated on CT. CONCLUSIONS: There is little correlation between septal deviation findings on CT scans and symptoms of nasal obstruction. The results do not support a role for CT scans as either a clinically meaningful or necessary test to investigate uncomplicated nasal obstruction. LEVEL OF EVIDENCE: 4.

Use of tissue ultrafiltration for treatment of compartment syndrome: a pilot study using porcine hindlimbs.

OBJECTIVES: To demonstrate the efficacy of compartment syndrome ultrafiltration for the treatment of acute compartment syndrome in an animal model. Our hypothesis is the removal of interstitial fluid will result in a reduction of intramuscular pressure compared with untreated controls in a model of bilateral induced compartment syndrome. DESIGN: Controlled experimental model. SETTING: Animal research facility. PATIENTS/PARTICIPANTS: Three pairs of porcine hindlimbs. INTERVENTION: Acute compartment syndrome was created in the pig hindlimb by infusion of saline to maintain the intramuscular pressure 30 mm Hg greater than the animal's mean arterial pressure for 8 hours. After a 2-hour reperfusion interval, ultrafiltration (removal of fluid through 1 mm diameter porous catheters, connected to -500 mm Hg suction) was commenced in 1 limb only and continued for 9.5 hours. MAIN OUTCOME MEASURES: Intramuscular pressure, ultrafiltrate volume, ultrafiltrate and serum levels of creatine kinase and lactate dehydrogenase, histologic measurement of extracellular and intracellular edema, as well as the degree of cellular necrosis. RESULTS: Intramuscular pressure tended to be lower on the treated side at the end of the treatment period [treated leg: 9.3 +/- 4.0 mm Hg (+/- SE), control leg: 19.3 +/- 1.4 mm Hg, P = 0.03]. Analysis of ultrafiltrate fluid showed that levels of creatine kinase and lactate dehydrogenase were elevated compared with serum levels. Creatine kinase levels in serum were measured at 4150 +/- 780 U/L, whereas ultrafiltrate levels of creatine kinase were 28,700 +/- 17,700 U/L (+/- SE) (P = 0.1). Lactate dehydrogenase was measured at 1950 +/- 180 U/L in serum, but markedly elevated in ultrafiltrate [160,000 +/- 88,900 U/L (+/- SE), P = 0.05]. Quantification of cellular and interstitial dimensions showed no difference in control and experimental limbs. Quantification of the degree of muscle necrosis revealed 6.1 +/- 2.7% necrosis in the treated limb compared to 11.3 +/- 1.6% necrosis in the control group (P = 0.02, df = 2, 1-tailed paired t test). CONCLUSION: This pilot study demonstrates the feasibility of tissue ultrafiltration for reduction of intramuscular pressure in this porcine model. Further studies are underway. Compartment syndrome ultrafiltration may be useful prophylactically in patients at risk for acute compartment syndrome. Sampling of interstitial fluid and frequent measurement of intramuscular pressure may allow earlier diagnosis and treatment of acute compartment syndrome, whereas the reduction of tissue pressure by compartment syndrome ultrafiltration may prevent acute compartment syndrome from occurring. Additionally, compartment syndrome ultrafiltration will not hinder the ability of clinicians to use the clinical examination and pressure monitoring as the gold standard.

Hyperbaric oxygen therapy: a meeting place for medicine and dentistry.

The hyperbaric medicine facility at Hennepin County Medical Center has been serving patients from throughout the region for more than 40 years. Some of these patients have head and neck cancer and are suffering delayed complications of radiation therapy. Such patients are often referred by dentists, oral surgeons, and otolaryngologists. This article summarizes outcomes for patients who have received hyperbaric oxygen therapy for 3 conditions: soft-tissue radiation injury before undergoing dental extractions, osteoradionecrosis, and soft-tissue radiation injury prior to receiving dental implants in the irradiated area.

Mirror-image reversal of coronal computed tomography scans.

OBJECTIVES/HYPOTHESIS: Mirror-image reversal of coronal computed tomography (CT) scans can be a significant problem in patient care, potentially leading to wrong-sided surgery and malpractice suits. There is no literature describing the problem of mirror-image reversal of coronal CT scans. Generally, medical errors are not widely published: however, with the emphasis on reduction of errors in medicine, this topic should be openly discussed. STUDY DESIGN: Retrospective review of patient care and an assessment of current methods. METHODS: Two cases of mirror-image reversal of coronal CT scans were reviewed, and the authors found that each case represented a different type of error. In the first case, the error was recognized in the operating room. The second case resulted in wrong-sided surgery, and a lawsuit was filed. These two separate occurrences led to a review of the methods for determining right versus left side for orienting and labeling of CT scans. Orientation of coronal scans depends on whether the patient is prone or supine. Thus, technician input is required. If a labeling mistake is made, radiologists may not readily catch the mistake because of the symmetry of the head and neck anatomy. RESULTS: A review of the markings on each scan should provide the otolaryngologist with enough information to determine whether the scan is mislabeled. CONCLUSION: The incidence of mislabeled coronal CT scans is unknown. This error can result in inappropriate patient care and lawsuits for wrong-sided surgery. Awareness of the potential problem and open discussion of interpretation and prevention are necessary.

Effect of tissue ultrafiltration on skin flap survival.

OBJECTIVE: Tissue ultrafiltration (TUF) is a method of reducing tissue edema by removal of interstitial fluid. Considering the deleterious effects of edema on microcirculation and tissue viability, the effect of TUF on skin flap survival was tested. STUDY DESIGN AND SETTING: Survival of modified McFarlane skin flaps was determined in 40 Sprague-Dawley rats. In 20 treated animals, four 5-cm ultrafiltration catheters were placed in the subdermal plane of the distal flap 24 hours after flap elevation and connected to a down-regulated vacuum manifold for 8 hours. No catheters were placed in the control group. RESULTS: Skin flap survival was improved in the experimental group (87.2 +/- 1.6) over the control group (76.7 +/- 2.2). DISCUSSION: TUF effectively improved skin flap survival. These results provide evidence of the causal effect of edema on tissue viability. The relative ease of use of TUF would allow cost-effective clinical application of this technique.