How Do head and neck cancer patients prioritize treatment outcomes before initiating treatment?

PURPOSE: To determine, pretreatment, how head and neck cancer (HNC) patients prioritize potential treatment effects in relationship to each other and to survival and to ascertain whether patients' preferences are related to demographic or disease characteristics, performance status, or quality of life (QOL). PATIENTS AND METHODS: One hundred thirty-one patients were assessed pretreatment using standardized measures of QOL (Functional Assessment of Cancer Therapy-Head and Neck) and performance (Performance Status Scale for Head and Neck Cancer). Patients were also asked to rank a series of 12 potential HNC treatment effects. RESULTS: Being cured was ranked top priority by 75% of patients; another 18% ranked it second or third. Living as long as possible and having no pain were placed in the top three by 56% and 35% of patients, respectively. Items that were ranked in the top three by 10% to 24% of patients included those related to energy, swallowing, voice, and appearance. Items related to chewing, being understood, tasting, and dry mouth were placed in the top three by less than 10% of patients. Excluding the top three rankings, there was considerable variability in ratings. Rankings were generally unrelated to patient or disease characteristics, with the exception that cure and living were of slightly lower priority and pain of higher priority to older patients compared with younger patients. CONCLUSION: The data suggest that, at least pretreatment, survival is of primary importance to patients, supporting the development of aggressive treatment strategies. In addition, results highlight individual variability and warn against making assumptions about patients' attitudes vis-à-vis potential outcomes. Whether patients' priorities will change as they experience late effects is currently under investigation.

Nanoparticle distribution during systemic inflammation is size-dependent and organ-specific.

This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.

Pre-incubation of synaptosomes with arachidonic acid potentiates inhibition of [3H]D-aspartate transport.

The ability of low micromolar concentrations of the polyunsaturated fatty acid, arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid) to inhibit the high-affinity, sodium-dependent transport of [3H]D-aspartate into purified synaptosomes of rat brain has been examined. Pre-incubation of the synaptosomes with arachidonic acid for 10-60 min produced a marked potentiation of the response to 10 microM arachidonic acid compared to co-incubation, and the threshold for inhibition of [3H]D-aspartate transport occurred at a concentration of 1 microM. Minimal inhibition of transport was seen with the unsaturated fatty acids, cis-oleic (cis-9-octadecenoic acid) and cis-linolenic (cis-9,12,15-octadecatrienoic acid), nor with the 20-carbon saturated fatty acid, arachidic acid (n-eicosanoic acid). Inclusion of the cyclo-oxygenase inhibitor, nor-dihydroguaretic acid (NDGA), in the presence of 5 microM arachidonic acid did not alter the inhibition of [3H]D-aspartate transport between 0-10 min, but did enhance the response at longer pre-incubation times. Inhibition of [3H]D-aspartate transport by arachidonic acid persisted during addition of the calcium ionophore, A23187, whereas removal of calcium ions from the incubation medium potentiated the response to arachidonic acid. The results are discussed in terms of the physiological relevance of the inhibition of glutamate transport by arachidonic acid, and suggest that regulation of inhibition of the glutamate transporter by arachidonic acid may be achieved by changes in the extracellular, as well as the intracellular, concentration of calcium ions.

Pars plana Baerveldt tube insertion with vitrectomy in glaucomas associated with pseudophakia and aphakia.

PURPOSE: We reviewed the course of intraocular pressure, visual acuity, and complications in patients with shallow anterior chambers or vitreous prolapse who underwent insertion of glaucoma drainage tubes through the pars plana (after a complete posterior vitrectomy). METHODS: Thirteen patients (13 eyes) with uncontrolled glaucoma associated with shallow anterior chamber or vitreous prolapse and aphakia or pseudophakia underwent pars plana Baerveldt tube insertion after vitrectomy. RESULTS: In 11 eyes the intraocular pressure was less than or equal to 15 mm Hg at a minimum follow-up of one year; the other two eyes underwent additional glaucoma surgery. Two of the 11 eyes with controlled intraocular pressure had limitation of ocular motility postoperatively. No retinal complications had occurred in any of the 13 eyes. CONCLUSION: This technique of combined pars plana vitrectomy and pars plana insertion of a Baerveldt tube provides intraocular pressure control in eyes with shallow anterior chamber or vitreous prolapse and glaucoma associated with pseudophakia or aphakia.

Inhibition of the high-affinity uptake of D-[3H]aspartate in rate by L-alpha-aminoadipate and arachidonic acid.

The mechanism of inhibition of the high-affinity sodium-dependent transport of D-[3H]aspartate by the gliotoxin, L-alpha-aminoadipate, and also by the endogenous fatty acid, arachidonic acid (cis-5,8,11,14 eicosatetraenoic acid), into rat brain synaptosomes has been investigated. L-alpha-Aminoadipate competitively inhibited the transport of D-[3H]aspartate with a K1 value of 192 microM. Superfusion of coronal slices of rat brain for 40 min with 1 mM L-alpha-aminoadipate reduced the glutathione concentration of the tissue by 20%. Neither glutamate nor kainate depleted the glutathione level of the slices. Pre-incubation of synaptosomes with arachidonic acid (10 microM) for 10-60 min produced a marked potentiation of the inhibition of D-[3H]aspartate transport, compared to experiments in which the acid was added concurrently with the D-[3H]aspartate ('co-incubation' experiments). Inhibition of D-[3H]aspartate transport by arachidonic acid was not blocked by addition of nordihydroguaretic acid to the pre-incubation medium. Staurosporine (50 nM) reduced the inhibition of transport occurring during pre-incubation with 10 microM arachidonic acid, and there was no longer any significant difference from the level of inhibition obtained in co-incubation experiments. Phorbol, 12-myristate, 13-acetate (1 microM) reduced the transport of D-[3H]aspartate to 73% of control after 20 min pre-incubation of the synaptosomes. This study highlights the fact that inhibition of glutamate transport may affect brain function in a number of different ways. Competitive inhibition by a structural analogue of glutamate, such as L-alpha-aminoadipate, leads to a reduction in the glutathione level, which may be an important factor in L-alpha-aminoadipate-mediated toxicity. On the other hand, the more long-term effects of non-competitive inhibition of glutamate transport by arachidonic acid, in a mechanism involving protein kinase C, may represent a physiological means for regulation of transporter activity in the brain.

Reproductive function in relation to duty assignments among military personnel.

As a follow-up to the pilot study of semen quality of soldiers with various military assignments a larger, more complete study was conducted. Soldiers were recruited at Fort Hood, Texas. Thirty-three men were exposed to radar as part of their duty assignment in the Signal Corps, 57 men were involved with firing the 155 mm howitzer (potential lead exposure), and 103 soldiers had neither lead nor radar exposure and served as the comparison control group. Both serum and urinary follicle-stimulating hormone and luteinizing hormone and serum, salivary, and urine testosterone levels were determined in all men. A complete semen analysis was conducted on each soldier. For statistical analysis, the primary study variables were: sperm concentration, sperm/ejaculate, semen volume, percent normal morphology, percent motile, percent viable (both vital stain and hypoosmotic swelling), curvilinear velocity, straight-line velocity, linearity, sperm head length, width, area, and perimeter. Variables were adjusted for significant confounders (e.g., abstinence, sample age, race). No statistical differences (P < 0.05) were observed in any measurement. While these results are in agreement with two previous studies assessing soldiers firing the 155-mm howitzer, they contradict our previous report indicating that radar exposure caused a significant decrease in sperm numbers. A possible explanation is that the radar exposure in this study was that used in Signal Corps operations while the men in the previous study were using different radar as part of military intelligence operations. The data presented here in men firing the 155-mm howitzer combined with the results from the previous studies confirms that there are no deficits in semen quality in these men. The contradiction between the results of the radar exposure studies indicates that more data are needed to evaluate the relationship of military radar and male reproductive health.

Reconstruction of the stenotic hypopharynx and cervical esophagus without total laryngectomy.

Reconstruction for severe stenosis of the hypopharynx, laryngeal inlet, and/or cervical esophagus is a challenging problem for the surgeon and his patient who want to avoid total laryngectomy. We reviewed the case records of eight patients and the relevant published literature in an effort to define the requirements for success and the causes of failure. A variety of surgical techniques were used. Seven of 8 patients eat a normal or near normal diet. Two of 4 patients, who sustained laryngeal damage at the time of initial injury, required total laryngectomy because of persistent aspiration. The 2 remaining patients and the 4 patients, who did not sustain laryngeal damage at the time of injury, speak with a good voice. Total laryngectomy should be reserved for those patient who cannot be rehabilitated following optimal reconstruction.

Speech restoration and complications of primary versus secondary tracheoesophageal puncture following total laryngectomy.

The tracheoesophageal (TE) fistula with a speech prosthesis has become the method of choice for vocal rehabilitation in many postlaryngectomy patients. Several modifications of the procedure have been described including primary TE puncture at the time of laryngectomy. Fear of increased risk of complications has kept the primary procedure from widespread usage. Our series of 95 TE fistula procedures from 1980 to 1988 revealed 33 to be primary and 62 secondary. Eighty-five percent (85%) (28 of 33) patients in the primary group achieved long-term satisfactory speech (1 year or more of follow-up). Complications occurred in 36% of this group of patients. The success rate for the secondary group was 69% (43 of 62), while the complication rate was 21%. There were no instances of death, sepsis, or mediastinitis associated with either primary or secondary TE fistula patients. It appears that the primary TE fistula can be performed as safely and effectively as the secondary procedure.

Longitudinal evaluation of vocal function after thyroplasty type I in the treatment of unilateral vocal paralysis.

This study investigated longitudinal changes of vocal efficiency and stability after primary thyroplasty type 1. Fifty-three patients with unilateral vocal-fold paralysis underwent vocal-function evaluation preoperatively and at periodic intervals of 1, 3, and 6 months postoperatively. Vocal-function assessment included videostrobolaryngoscopic examination, acoustical and aerodynamic analysis, and perceptual judgment of voice characteristics. Parameters that included glottic-gap size, maximum phonation time, glottic-flow rate, jitter, harmonic/noise ratio, breathiness, hoarseness, loudness, and phrasing showed significant improvement after thyroplasty and remained stable as early as 1 month postoperatively, with only slight fluctuations over a 6-month period. Postoperative voice outcome was not affected by age, sex, duration of vocal symptoms, cause of paralysis, or preoperative pulmonary function.

Tissue plasminogen activator and glaucoma drainage implants.

PURPOSE: The tube lumen of a glaucoma drainage implant is prone to occlusion by a blood or fibrin clot due to its small caliber, relatively low flow rate, and the plasmoid nature of the aqueous humor passing through it in the early postoperative period. The use of tissue plasminogen activator in the management of drainage tube obstruction is described herein. METHODS: Two cases of drainage tube obstruction in patients with neovascular glaucoma treated with an intracameral injection of tissue plasminogen activator are reported. RESULTS: Resolution of tube obstruction following tissue plasminogen activator administration with spontaneous lowering of the intraocular pressure and bleb formation was achieved in both cases. Differentiation of tube obstruction from other causes of elevated intraocular pressure following installation of glaucoma drainage devices is discussed. CONCLUSION: The intracameral injection of tissue plasminogen activator may relieve drainage tube obstruction secondary to a blood or fibrin clot, even in the absence of any visible clot covering the proximal tube ostium or within the anterior chamber portion of the tube. This approach should be considered, in selected cases, prior to more invasive surgical revision.

Sacral fixation technique in lumbosacral fusion.

STUDY DESIGN: Servohydraulic load displacement testing was used to study the biomechanical properties of sacral fixation in human cadaveric specimens. OBJECTIVES: To evaluate a modification of standard sacral fixation that uses the first dorsal sacral foramina as an adjunct location for the placement of a sacral hook in addition to S1 pedicle screws. BACKGROUND DATA: The stiffness or rigidity of an instrumentation construct governs the amount of relative movement allowed between motion segments undergoing fusion. This property provides the greatest influence over the mechanical conditions necessary for fusion to occur. METHODS: Sixteen human cadaveric specimens were divided into two groups with similar bone density assessed by quantitative computed tomography scan. All were instrumented with pedicle screws at L4 and S1. One group also had downgoing offset hooks in the first sacral foramina distracted against the S1 pedicle screw. Instron servohydraulic testing was performed in anterior compressive flexion, and load displacement curves were recorded. RESULTS: The bending stiffness of the specimens instrumented with screw and hook was significantly higher than in those instrumented with pedicle screws alone. The ultimate strength and energy absorbed did not differ between the two groups. CONCLUSIONS: The addition of sacral foraminal hooks to standard pedicle screw instrumentation constructs across the lumbosacral junction provides more rigid stabilization of the lumbosacral motion segment in this model.

Neurological deterioration after posterior wiring of the cervical spine.

Posterior cervical wiring is commonly performed for patients with spinal instability, but has inherent risks. We report eight patients who had neurological deterioration after sublaminar or spinous process wiring of the cervical spine; four had complete injuries of the spinal cord, one had residual leg spasticity and three recovered after transient injuries. We found no relation between the degree of spinal canal encroachment and the severity of the spinal-cord injury, but in all cases neurological worsening appeared to have been caused by either sublaminar wiring or spinous process wiring which had been placed too far anteriorly. Sublaminar wiring has substantial risks and should be used only at atlantoaxial level, and then only after adequate reduction. Fluoroscopic guidance should be used when placing spinous process wires especially when the posterior spinal anatomy is abnormal.

Efficacy of videostroboscopy in the diagnosis of voice disorders.

While videostrobolaryngoscopy is not a new technique, its acceptance as a routine part of the voice evaluation has not been as forthcoming. Many are in agreement that the rigid fiberoptic telescopes in combination with standard VHS equipment provide a clear, magnified image that can be recorded and used for pretreatment and post-treatment comparisons, documentation, teaching, and research. Yet, some skepticism persists with regard to the ability of videolaryngoscopy and/or videostrobolaryngoscopy in changing the diagnosis and treatment outcome of patients with voice disorders as compared to indirect laryngoscopy. Two hundred ninety-two dysphonic patients were identified who underwent indirect as well as videolaryngoscopy with and without stroboscopic examination. Videostrobolaryngoscopy was found to alter the diagnosis and treatment outcome in 14% of the patients. It is most useful in patients with a diagnosis of functional dysphonia and vocal fold paralysis by indirect laryngoscopy. The increased illumination and magnification afforded by rigid fiberoptic telescopes during videolaryngoscopy, combined with the detailed assessment of glottic closure, mucosal wave, and amplitude characteristics provided by stroboscopic examination, allowed detection of subtle vocal fold pathology, otherwise missed by indirect laryngoscopy.

A fine-cut technique for permanent laryngeal sectioning.

BACKGROUND: A new technique for permanent sectioning of the human spinal cord has provided superior images over those produced with traditional methods. Application of this technique for sections of the human larynx may yield cost-effective, efficient, and accurate laryngeal anatomic dissections. STUDY DESIGN AND METHODS: This study was designed to evaluate this technique for dissections of the human larynx. Laryngeal sections from cadavers were submerged in a celloidin solution, a derivative of wallpaper plaster, and frozen to -15 degrees C. After preparation, axial and coronal cuts of 100 microm were made with a Macrocut Tome sectioning system. RESULTS: Sections were completed in approximately 30 hours. Digitized photographs of the laryngeal sections provide detailed images of precise anatomic relationships. CONCLUSION: Celloidin-based sectioning of the human larynx yields precise anatomic information beyond standard radiographic imagining and previous permanent laryngeal sectioning techniques in a cost-efficient and timely manner. Black and white fine-section photographs are provided.

Thyroplasty type I: short- versus long-term results.

OBJECTIVE: After thyroplasty type I, significant improvement has been reported in objective measures of vocal function. The purpose of this investigation was to compare the short- and long-term results in patients undergoing thyroplasty type I. METHODS: Data on 26 patients who had undergone thyroplasty type I for management of unilateral vocal fold paralysis were compared from before surgery to the short-term (1-month) and long-term (>1-year) postoperative assessment points. Statistical analysis included paired tests to assess the significance of between-group differences. RESULTS: Significant differences were found between the preoperative and both postoperative evaluations for the measures of mean glottal flow rate, maximum phonation time, jitter, shimmer, and harmonic-to-noise ratio. However, no significant differences were found between the 1-month and >1-year assessment points. CONCLUSIONS: The results for the parameters studied appeared to reach maximum improvement within 1 month after surgery. It is possible that the effects of time, including the normal aging process, hormonal changes, or other alterations in general health, may require longer follow-up to better address these issues.

Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings.

Fifty-three patients underwent laser cordectomy for T1 glottic squamous cell carcinoma between January 1980 and December 1989--sixteen after having undergone unsuccessful radiation and thirty-seven who had no previous treatment. There was a 51% five-year cure rate in the irradiated group vs. 62% in the nonirradiated group. Extension of tumor to the anterior commissure resulted in a higher failure rate. Patients experienced an overall 5-year cure rate of 98% after surgical or radiation salvage of unsuccessful laser cordectomies. Six patients had preoperative and postoperative videostrobolaryngoscopy. The most common postoperative problem with voice was a breathiness that did not resolve in any of the patients. All patients had absent or moderately reduced amplitude and mucosal wave patterns and imcomplete glottic closure proportional to the amount of cordal tissue removed. Despite it seemingly poor results in carefully selected patients, laser cordectomy is still indicated without compromising the ultimate oncologic results. Advantages over radiation therapy or conservation laryngeal surgery include a short treatment time, requiring only an outpatient surgical procedure at the time of the initial diagnostic and/or staging laryngoscopy, and the avoidance of potential radiation side effects or surgical complications. However, patients should be advised the possibility of persistent postoperative breathy dysphonia, in addition to the possibility of further treatment to effect a long-term cure.

Cause of hoarseness in elderly patients.

Hoarseness is a common symptom in older individuals and may reflect a wide variety of pathologic, medical, physiologic, and/or functional causes. Although vocal fold atrophy is one of the more common reported findings in the elderly, inconclusive information is known about the differential diagnosis and cause of dysphonia in older individuals. The purpose of this investigation was to review the cause of hoarseness in all patients older than 65 years and to determine any correlation with advancing age and other demographic factors. Additionally, we wanted to determine the effect vocal pathology has on objective voice measures with advancing age. The two most common causes of hoarseness found in 393 patients older than 65 years were vocal fold bowing and unilateral vocal fold paralysis, followed by benign vocal fold lesions, voice tremor, and spasmodic dysphonia. Although objective measures of vocal function were abnormal compared with reported normative data, they did not increase in severity with advancing age. Apparently, the compounding effect of age on underlying vocal pathology does not increase the severity of the vocal disturbance, at least as represented by objective voice measures. The high incidence of medical illnesses seen in this population also needs to be kept in mind because it may further affect the underlying voice disturbance. It might be interesting to compare data on the patients' perceptions of their vocal disturbance for each disorder as a function of age. It would also be helpful to know whether patients responded to treatment differentially based on age.

Incidence of abnormal laryngeal findings in asymptomatic singing students.

OBJECTIVE: Abnormalities in the mucosal lining of the vocal folds may interfere with the normal vibratory patterns and result in vocal limitations, especially for singers whose demands are great. A prospective, longitudinal study was undertaken to investigate the incidence of laryngeal abnormalities in asymptomatic singing students. METHODS: Sixty-five singing students at the school of music underwent videostroboscopic evaluation and completed a comprehensive questionnaire. Videos were rated by 3 experienced clinicians, and interrater reliability was calculated. Results were correlated with demographic factors, background medical history, and singing history. RESULTS: Five students (8.3%) exhibited early signs of benign vocal fold lesions (2 with nodules and 3 with cysts). A high incidence of posterior erythema (n = 44; 73.4%), suggesting possible reflux, was found. CONCLUSIONS: A surprisingly high number of otherwise asymptomatic singing students demonstrated abnormal laryngeal findings. Their relationship with vocal performance will be addressed as well as implications for preventative measures.

Aspiration: cause and implications.

The purpose of this investigation was to determine the overall prevalence of aspiration in dysphagic individuals referred for a modified barium swallow and the underlying anatomic and/or physiologic causes. A total of 166 patients were seen during a 1-month period at 5 participating institutions. Aspiration was detected in 51.2% of the patients. The most common causes were decreased laryngeal elevation and delayed triggering of the pharyngeal motor response. A history of aspiration pneumonia was significantly associated with the presence of aspiration on modified barium swallow study. The presence of a protective cough was present in only 53% of patients who aspirated, reinforcing the need for appropriate radiologic assessment in patients with suspected dysphagia.

"Floating knee" injuries: ipsilateral fractures of the femur and tibia.

Ipsilateral fractures of the femur and tibia have been called "floating knee" injuries and may include combinations of diaphyseal, metaphyseal, and intra-articular fractures. These are often high-energy injuries and most frequently occur in the polytrauma patient. Many of these fractures are open, with associated vascular injuries. Surgical stabilization of both fractures and early mobilization of the patient and the extremity produce the best clinical outcomes. The use of a radiolucent operating room table and the introduction of retrograde intramedullary fixation of femoral fractures have facilitated surgical stabilization of some floating-knee fracture patterns. Although treatment planning for each fracture in the extremity should be considered individually to achieve the optimal result, the effect of that decision must be considered in light of the overall injury status of the entire extremity. Collateral ligament and meniscal injuries may also be associated with this fracture complex. Complications (such as compartment syndrome, loss of knee motion, failure to diagnose knee ligament injury, and the need for amputation) are not infrequent. Better results and fewer complications are observed when both fractures are diaphyseal than when one or both are intra-articular.