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Samuel J Hassenbusch

Publications and source records attributed to Samuel J Hassenbusch.

16 recordsLinked to original sources
PubMed2004

Stereotactic radiosurgical treatment in 103 patients for 153 cerebral melanoma metastases.

PURPOSE: To report on the outcome of patients with melanoma brain metastases treated with stereotactic radiosurgery (SRS). PATIENTS AND METHODS: One hundred three patients with 153 intracranial melanoma metastases consecutively underwent Linac-based SRS between November 1991 and October 2001. The Kaplan-Meier method, univariate comparisons with log-rank test, and multivariate analyses with classification and regression tree models were performed. Calculations were based on last imaging date rather than the date of the last visit. RESULTS: Median age was 51 years (range, 18-93 years). Median Karnofsky performance status was 90. Sixty-one patients (59%) had single brain metastasis at presentation. Treatment sequence was SRS alone (61 patients), SRS + whole-brain radiotherapy (WBRT) (12 patients), and salvage SRS after WBRT (30 patients). The median tumor volume was 1.9 cm(3) (range, 0.06-22.3 cm(3)). The median SRS minimum peripheral dose and isodose was 18 Gy (range, 10-24 Gy) and 85% (range, 60%-100%), respectively. The median follow-up was 6 months for all patients and 13 months (range, 2-46 months) for patients alive at the time of analysis. The 1-year local control (LC) for all patients treated with SRS was 49%. Among the patients treated with initial SRS alone, the 1-year LC was better for patients with tumors < or =2 cm(3) than with tumors >2 cm(3): 75.2% vs. 42.3% (p < 0.05). The 1-year distant brain metastasis-free survival incidence was 14.7% for the 73 patients receiving either initial SRS alone or SRS +WBRT. The initial number of brain lesions (single vs. multiple) was the only factor with a significant effect on distant brain metastasis-free survival at 1 year: 23.5% for single metastases and 0% for multiple lesions (p < 0.05). The 1-year overall survival was 25.2%. Stratification by Score Index for Radiosurgery (SIR) revealed a significant effect on survival, which was 29% at 1 year for SIR >6 and 10% for SIR <==6 (relative hazard ratio, 2.1; p < 0.05) in classification and regression-tree multivariate analysis involving age, Karnofsky performance status, primary tumor control, tumor volume, SRS dose, SIR (>6 vs. < or =6), and systemic disease status. CONCLUSIONS: Initial SRS alone was an effective treatment modality for smaller cerebral melanoma metastases, achieving a 75% incidence of 1-year LC for < or =2 cm(3) single brain metastases and should be considered in patients with SIR >6. The role of WBRT in melanoma brain metastases cannot be addressed, owing to retrospective bias toward administering this treatment to patients with more aggressive disease. A prospective study is needed to assess the role of WBRT in patients with melanoma brain metastasis.

Adolescent↗
PubMed2004

Spinal cord stimulation relieves chemotherapy-induced pain: a clinical case report.

We present two patients with chemotherapy-induced painful neuropathy that had been poorly controlled with medications but successfully treated with spinal cord stimulation (SCS). A trial period of SCS provided effective pain relief in both patients who subsequently underwent permanent stimulator implantation. Psychophysical tests were performed before and after the implantation of trial and permanent stimulators. SCS improved pain scores and facilitated a reduction of medications. Both patients reported improved gait and one of them also reported an increase in leg flexibility. Psychophysical tests demonstrated an improvement in touch and sharpness detection thresholds. In summary, SCS offers a therapeutic option for patients with chemotherapy-induced peripheral neuropathy who have poor pain relief with standard medical treatment.

Aged↗
PubMed2004

Polyanalgesic Consensus Conference 2003: an update on the management of pain by intraspinal drug delivery-- report of an expert panel.

Intraspinal drug infusion using fully implantable pump and catheter systems is a safe and effective therapy for selected patients with chronic pain. The options for this approach are increasing, as drugs that are commercially available for systemic administration are adapted to this use and other drugs that are in development specifically for intraspinal administration become available. In 2000 a Polyanalgesic Consensus Conference was organized to evaluate the existing literature and develop guidelines for drug selection. The major outcome of this effort, an algorithm for drug selection, was based on the best available evidence at the time. Rapid changes have occurred in the science and practice of intraspinal infusion and a Polyanalgesic Consensus Conference 2003 was organized to pursue the following goals: 1) to review the literature on intraspinal drug infusion since 1999, 2) to revise the 2000 drug-selection algorithm, 3) to develop guidelines for optimizing drug dosage and concentration, 4) to create a process for documenting minimum evidence supporting the use of a drug for intraspinal infusion, and 5) to clarify issues pertaining to compounding of drugs. Based on the best available evidence and expert opinion, consensus recommendations were developed in all these areas. The panel's conclusions may provide a foundation for clinical practice and a rational basis for new research.

Algorithms↗
PubMed2004

Continuous intrathecal infusion of hydromorphone: safety in the sheep model and clinical implications.

OBJECTIVE: To determine the safety of hydromorphone delivered by continuous intrathecal infusion via implanted delivery systems in sheep. DESIGN: Sheep implanted with intrathecal infusion systems were randomly assigned to receive either 1.5, 3, or 6 mg/day hydromorphone HCl or saline control (3 sheep/dose level) at a fixed infusion rate of 1.92 mL/day for 28-31 days. Infusions were initiated approximately 5 days after surgical implantation of the delivery systems (pumps and intrathecal catheters), and investigators were blinded to doses administered. An additional group of sheep (N=3) received hydromorphone (open label) at a dose of 12 mg/day. All animals were examined daily during drug infusion for changes in behavior and neurologic function. Cerebrospinal fluid was analyzed for protein, cytology, and hydromorphone concentration in samples collected prior to and at the end of drug infusion. The spinal cord with the catheter in situ was removed en bloc and fixed in formalin for microscopic analysis. RESULTS: All sheep receiving intrathecal hydromorphone exhibited gaiting deficits and biting behavior over the caudal lumbar area above the infusion site. Animals treated with 12 mg/day were sedate and lethargic, and exhibited repeated biting behavior over the caudal lumbar area during the study. No lesions were noted in any animal upon gross evaluation of the spinal cord. Microscopic changes were comparable between hydromorphone- and saline-treated animals with one exception. Mild inflammation 5 cm cranial to the catheter tip was present in two of three sheep receiving 12 mg/day and in one of three sheep receiving 1.5 mg/day. Mild chronic inflammation hydromorphone in the vicinity of the catheter was also presented in saline-treated animals. CONCLUSIONS: Hydromorphone was not associated with inflammatory mass formation in the sheep model. Further studies are necessary to determine whether hydromorphone is a safer alternative to morphine for continuous intrathecal infusion for the treatment of chronic pain.

Animals↗
PubMed2004

Epidural and intrathecal analgesia is effective in treating refractory cancer pain.

The use of neuraxial (intrathecal and epidural) analgesia has been suggested in treatment guidelines put forth for the treatment of refractory cancer pain. We review the literature and present our algorithm for using neuraxial analgesia. We also present our outcomes using this algorithm over a 28-month period. We used neuraxial analgesia in 87 of 4,107 patients, approximately 2% of those seen for pain consultation. Evaluation of those patients at an 8-week follow-up revealed improved pain control. After institution of neuraxial analgesia, there was a significant reduction in the proportion of patients with severe pain (defined as a "pain worst" score in the severe range of 7-10), from 86% to 17%, noted to be highly statistically significant. At follow-up, numerical pain scores decreased significantly from 7.9 +/- 1.6 to 4.1 +/- 2.3. No difference was noted between the intrathecal and epidural groups. Oral opioid intake after instituting neuraxial analgesia revealed a significant decrease from 588 mg/day oral morphine equivalents to 294 mg/day. At follow-up, self-reported drowsiness and mental clouding (0-10) also significantly decreased from 6.2 +/- 3.0 and 5.4 +/- 3.4 to 3.2 +/- 3.0 and 3.1 +/- 3.0, respectively. This retrospective review shows promising efficacy of neuraxial analgesia in the context of failing medical management.

Algorithms↗
PubMed2004

Safety of continuous intrathecal midazolam infusion in the sheep model.

UNLABELLED: We investigated the safety of midazolam administered by continuous intrathecal infusion in relevant animal models. Preservative-free midazolam was delivered to sheep and pigs by using implanted infusion systems (SynchroMed pumps plus silicone catheters). Sheep received midazolam 5 mg/d (n = 4) or 15 mg/d (n = 7) or saline (n = 2) for 43 days at 125 micro L/h. One sheep received 10 mg/d. Infusion concentrations ranged from 1.7 to 2.5 mg/mL (5 mg/d) and from 2.5 to 5.0 mg/mL (15 mg/d). Pigs were evaluated for toxicity only and received 15 mg/d (n = 2) or saline (n = 1) for 43 days at 125 micro L/h. Behavior, neurologic function, and vital signs were documented. Serum and cerebrospinal fluid chemistry and cytology were evaluated, and histology was performed on spinal cord tissue. Behavior and neurologic function remained normal in all subjects. Gross and microscopic evaluation of spinal tissue revealed mild inflammation surrounding the catheter tract in both the midazolam-treated and the saline-treated groups. This inflammation was likely attributable to the mechanical presence of the catheter. These data demonstrate that continuous intrathecal infusion of preservative-free midazolam at doses up to 15 mg/d were well tolerated. IMPLICATIONS: We investigated the toxicity of preservative-free intrathecal midazolam delivered continuously via implanted infusion systems in sheep and pigs. Doses of 5-15 mg/d were well tolerated. The lack of neurotoxicity observed suggests that intrathecal midazolam may be an alternative for the treatment of intractable pain that is unresponsive to opioids.

Animals↗
PubMed2003

Stability and compatibility of morphine-clonidine admixtures in an implantable infusion system.

Nonopioid analgesics are often coadministered with intrathecal morphine to increase efficacy. The purpose of this study was to evaluate stability and compatibility of morphine-clonidine admixtures with an implantable infusion system that is commonly used to treat pain patients. Infusion systems were filled with admixture and maintained at 37 degrees C for 90 days. Samples were collected monthly. Drug concentrations were determined using stability-indicating, high-performance liquid chromatography. For compatibility testing, individual materials comprising the fluid pathway of the device were immersed in clonidine solution and stored at 37 degrees C for various periods through 64 weeks and mechanical performance evaluated. After 3 months of containment in the infusion system, morphine and clonidine concentrations remained at > or = 94% of the theoretical starting concentrations. All device materials retained acceptable mechanical performance following clonidine exposure. These results demonstrate that morphine and clonidine are stable when combined in aqueous solution maintained at body temperature in an implantable infusion system for at least 3 months.

Analgesics↗
PubMed2003

Spinal analgesics.

The important issues to be emphasized when considering the intrathecal administration of novel analgesics are their proven antinociceptive effect, safety (short- and long-term effects on the spinal cord and potential toxicities), stability in shelf solution and at body temperature by itself, or in combination with other drugs in spinal fluid, compatibility with a long-term spinal infusion pump, whether they are of sufficiently high potency and solubility to be used in the finite volume of an implanted infusion pump, and if a pharmaceutical company is willing to invest the immense resources needed for US Food and Drug Administration approval and subsequent commercial development.

Analgesics↗
PubMed2003

Safety of chronic intrathecal morphine infusion in a sheep model.

BACKGROUND: The safety of chronically administered intrathecal morphine has been questioned. Therefore, the authors examined the behavioral and neurologic effects and neurotoxicity of continuous intrathecal morphine administration in sheep. METHODS: Groups of three sheep were implanted with intrathecal infusion systems for the continuous administration of morphine (3, 6, 9, 12, or 18 mg/day) or saline at a fixed infusion rate of 1.92 ml/day beginning approximately 7 days after implantation. Sheep were examined daily for any changes in behavior or neurologic function. After 28-30 days, the animals were humanely killed. Cerebrospinal fluid samples were collected and analyzed for protein, erythrocytes and leukocytes, and morphine content. The spinal cord and meninges with the catheter in situ was removed en bloc and fixed in formalin for histologic analysis. RESULTS: Unilateral hind-leg gait deficits were observed in two of three animals in each of the 12- and 18-mg/day dose groups. Gross and microscopic evaluation of spinal cord tissue from these animals revealed intradural-extramedullary inflammatory masses that compressed the spinal cord at the catheter-tip and mid-catheter areas. This inflammation was ipsilateral to extremities that exhibited gait deficits and had acute and chronic cellular components. CONCLUSIONS: The toxicity of intrathecal morphine seems to be dependent on the amount of morphine infused, although the effects of dose versus concentration cannot be clearly distinguished in this study. Intrathecal morphine doses of 12- 18 mg/day produced inflammatory masses extending from the catheter tip down the length of the catheter within the subarachnoid space. Doses of 6-9 mg/day produced mild-to-moderate inflammation 5 cm cranial to the catheter tip. A dose of 3 mg/day produced no neurotoxicity and spinal histopathologic changes that were equivalent to those observed in the saline-treated animals.

Analgesics, Opioid↗
PubMed2003

The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases.

OBJECTIVE: To identify a size cutoff below which it is safe to observe obscure brain lesions suspected of being metastases so that treatment of nonmetastases can be avoided. METHODS: Medical records from patients who underwent linear accelerator-based radiosurgery from August 1991 to October 2001 were reviewed. Inclusion criteria were defined as brain metastasis tumor volume less than 5 cm(3) (diameter, thick similar 2.1 cm) treated with a dose of 20 Gy or more. One hundred thirty-five patients had 153 evaluable brain metastases with follow-up imaging that met inclusion criteria. Median age was 54 years (range, 18-79 yr). Lesion primaries were non-small-cell lung (n = 39), melanoma (n = 44), renal (n = 37), breast (n = 18), colon (n = 3), sarcoma (n = 5), other (n = 5), and unknown primary (n = 2). Median tumor volume was 0.67 cm(3) (range, 0.06-4.58 cm(3)). The minimum peripheral dose was 20 Gy (n = 132) or 21 to 24 Gy (n = 21). At the time of analysis, the median follow-up for all patients was 10 months (range, 0.2-99 mo). RESULTS: The 1- and 2-year actuarial local control rates for all of the lesions were 69 and 46%, respectively. For lesions of 1 cm (0.5 cm(3)) or less, the corresponding local control rates were 86 and 78%, respectively, which was significantly higher than the corresponding rates of 56 and 24%, respectively, for lesions larger than 1 cm (0.5 cm(3)) (P = 0.0016). CONCLUSION: A convincing brain metastasis measuring less than 1 cm should be pursued aggressively. If the suspected brain metastasis is ambiguous, observation is proposed up to a diameter of 1 cm. This is the first study in the literature to identify a 1-cm cutoff for radiosurgical control of small brain metastases, and validation by additional studies is required.

Actuarial Analysis↗
PubMed2003

Fusobacterial brain abscess: a review of five cases and an analysis of possible pathogenesis.

OBJECT: The cases of five patients with fusobacterial brain abscess are presented. The authors discuss their attempt to determine the pathogenesis. METHODS: The clinical and microbiological features of five cases of fusobacterial brain abscess are reviewed. Isolates of 2031 Fusobacterium spp. and other anaerobes collected (1989-2002) at our institution were analyzed and compared for incidences and isolation sources. The findings were correlated with extensive literature on the subject. The five patients were men between 45 and 74 years of age. All experienced an insidious onset of the disease and probable hematogenous seeding of the organism(s). One patient had a monomicrobic Fusobacterium necrophorum abscess, whereas the others had polymicrobic F. nucleatum abscesses. Despite surgery and a regimen of antibiotic medications and dexamethasone, three patients experienced a paradoxical deterioration 3 days postoperatively that necessitated reevacuation of the lesion. The evacuants observed at that time contained numerous leukocytes but no microorganisms, suggesting intensified inflammation as the likely cause of deterioration. This explanation is supported by literature that fusobacteria strongly activate neutrophils. An analysis of the 2031 anaerobes from blood, wounds, and abscesses showed the considerable virulence of Fusobacterium spp., which were able to enter and/or sustain themselves in the blood circulation. This pattern was similar to that of Clostridium spp., but different from those of Peptostreptococcus spp., Bacteroides spp., and Prevotella spp., which were less invasive but more abundant. CONCLUSIONS: Some fusobacterial brain abscesses may be associated with a paradoxical postoperative deterioration, which is probably due to intensified inflammation following treatment. The blood-borne dissemination and invasive behavior of fusobacteria likely initiate such a brain abscess, and further seeding of other synergic bacteria leads to a polymicrobic abscess.

Aged↗
PubMed2002

Intrathecal clonidine in the treatment of intractable pain: a phase I/II study.

OBJECTIVE: Epidural clonidine has been proven effective in relieving intractable cancer pain, especially neuropathic. This phase I/II study was performed to investigate if intrathecal clonidine is well tolerated and effective for long-term treatment of intractable chronic pain. DESIGN: Thirty-one patients, previously implanted with programmable pumps and unable to obtain adequate pain relief with opioids and adjuvant oral medications, were enrolled. Clonidine monotherapy was initiated at 1 mcg/hr and escalated to a maximum of 40 mcg/hr (960 mcg/day). Efficacy measurements included Verbal Digital Pain Ratings, and side effects were determined by physical exam and patient reports. RESULTS: Patients achieving 50% or greater reduction in pain intensity scores in the dose-titration phase continued for long-term follow-up. Twenty-two patients (71%) entered long-term follow-up with intrathecal clonidine; nine patients (29%) did not obtain adequate pain control in the dose-titration phase. Thirteen patients were considered long-term successes with a mean follow-up of 16.7 months (range = 6.3 to 44 months). Nine patients failed to achieve adequate pain relief due to side effects or lack of efficacy. Fifty-nine percent of the patients successful in the dose-titration stage (42% of all patients considered) were considered long-term successes. Patients in the long-term phase maintained adequate pain control with minimal dose escalation. CONCLUSIONS: This study demonstrates the tolerability and effectiveness of intrathecal clonidine in the treatment of chronic pain. The physician using clonidine for long-term intrathecal infusion should be cognizant of the risk that severe rebound systemic hypertension can occur with abrupt cessation of the intrathecal infusion of clonidine.

Journal Article↗
PubMed2002

Intractable vomiting from glioblastoma metastatic to the fourth ventricle: three case studies.

Dissemination of malignant glioma to the fourth ventricle with metastatic deposits and intractable vomiting is rare. Leptomeningeal extension of malignant glioma is an uncommon condition that has been reported in patients with end-stage disease and is usually unresponsive to any treatment modality. We describe 3 patients with progressing recurrent glioblastoma multiforme in whom leptomeningeal invasion manifested itself as intractable vomiting due to tumor metastases in the floor of the fourth ventricle. All patients received additional radiation therapy focused to the posterior fossa, with complete resolution of vomiting occurring within 10 days after irradiation. The remission of symptoms in these patients persisted until their death 3-4 months after the repeat radiation therapy. These reports indicate that additional focused radiation should be considered because of its significant therapeutic effect in alleviating intractable nausea and vomiting in patients with glioma metastasized to the posterior fossa.

Adult↗
PubMedDate not supplied

Stereotactic injection of DTI-015 into recurrent malignant gliomas: phase I/II trial.

DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the intratumoral treatment of gliomas. The ethanol solvent vehicle facilitates a rapid and thorough saturation of the tumor with the dissolved anticancer agent BCNU. We conducted a phase I/II dose escalation study of DTI-015 in 40 heavily pretreated patients with inoperable recurrent malignant glioma. The study goals were to establish a maximally tolerated dose (MTD) for DTI-015 and assess its safety and activity. Patients received stereotactic intratumoral injection of DTI-015 under magnetic resonance imaging guidance. Dose escalation was performed in two phases. First, DTI-015 volume was escalated at a set BCNU concentration of 12.5 mg/ml; second, BCNU mg dose was escalated by increasing BCNU concentration to 30, 45, 60, and 75 mg/ml. A MTD of 5 ml and 240 mg was established. Twenty-five of 28 DTI-015 treatments (89%) using </=MTD were administered safely without producing high-grade drug-related adverse events. Median survival for GBM patients administered DTI-015 at </=MTD was 55 weeks. Magnetic resonance imaging demonstrated stable disease in 72% of evaluable patients with a median of 10.5 weeks. The results suggest that DTI-015 administered at </=MTD is well tolerated and active in patients with inoperable recurrent GBM.

Adult↗