Phase II study with etoposide in previously untreated advanced breast cancer.

A phase II study was carried out to evaluate the efficacy and safety of etoposide used as first-line chemotherapy for patients with advanced breast carcinoma. A total of 20 patients received 230 mg/m2 i.v. etoposide per day for 3 days (total, 690 mg/m2 per course) every 4 weeks. A total of 95 courses were given. Observed responses included 3 partial remissions (PR) and 14 cases of stable disease (NC). The median duration of response was 6 (PR) and 5.6 months (NC). Contrary to the severe hematological toxicity in heavily pretreated patients described in previous studies, no substantial problems were observed in this trial. No dose reduction was necessary, and only once did leukopenia lead to a 1-week delay in therapy. An increase in platelets up to a maximum of 685,000/mm3 was seen in all patients, particularly in those with bone metastases. No relation to the quality of remission or pretreatment was seen. Nausea, vomiting, and fatique were mild and transient, but alopecia occurred in all cases. One patient developed nonfatal anaphylactic shock after etoposide treatment.

MR of the cauda equina.

To define the anatomy of the cauda equina nerve roots by MR imaging, the lower spine of 14 normal volunteers was imaged using a high-field surface-coil technique. A total of 56 sagittal and 56 axial MR sections (eight selected slices from each case) were correlated with undistorted anatomic sections from cadaver spine specimens, and the visualization of the nerve roots was assessed. In addition, MR images of three patients with infiltrating or seeding tumors affecting the cauda equina were analyzed. Seventy-eight percent of the MR sections from normal cases clearly showed the anatomy of the cauda equina nerve roots. The nerve roots were fairly shown in 17% of the sections; and false findings (presumably caused by CSF pulsation) were observed in the remaining 5%. Coronal imaging provided excellent anatomic views of the nerve roots within the intervertebral foramina. Morphologic alterations in the pathologic cases were correctly shown when both T1- and T2-weighted imaging were used. In conclusion, MR proved efficient in viewing the cauda equina region.

Multiplanar spinal anatomy: comparison of CT and cryomicrotomy in postmortem specimens.

Good anatomic knowledge is a prerequisite for correct interpretation of computed tomographic (CT) scans. To elucidate the complex CT anatomy of the spine, autopsy specimens from various spinal regions were frozen in situ to preserve the undistorted topographic anatomy. The frozen specimens were examined by CT in axial, sagittal, and coronal planes and sectioned by cryomicrotomy along the scanning planes. Photography of the section surfaces yielded detailed anatomic images that were accurately correlated with the CT scans.

Carboplatin. The better platinum in head and neck cancer?

Chemotherapeutic regimens containing cisplatin are the most effective ones in the treatment of squamous cell carcinoma of the head and neck. Because of the high rate of dose-limiting side effects of cisplatin, carboplatin, a second-generation cisplatin analogue, was tested in a phase II trial with fluorouracil in 55 previously untreated patients with advanced carcinoma of the head and neck. Among the 52 patients who completed the study, there were 17 complete responses (33%), 28 partial responses (54%), five patients with no change (10%), and two with progressive disease (4%). Toxic side effects of all courses summed together included leukopenia in 65% of courses, thrombocytopenia in 45% of courses, nausea or vomiting in 29% of courses, and change in serum creatinine level in 3% of courses. These data were compared with the results of our study with cisplatin and fluorouracil in comparable patients and indicated that carboplatin and fluorouracil is better for induction chemotherapy in the treatment of head and neck cancer than cisplatin and fluorouracil due to similar effectiveness but less toxic effect.

Normal and pathologic anatomy of the lumbar root canals.

Eighty-three degenerated human lumbar spines (274 segments) were frozen in situ, some after injection of contrast medium into the arteries or after functional positioning. No single orthogonal plane ideally displays the complex three-dimensional relationships in the long osseoligamentous lumbar root canals; detailed anatomic images were therefore obtained in axial, sagittal or coronal planes with a surface cryoplaning technique. Typical degenerative changes included bulging of the intervertebral discs, retropulsion of annulus fibrosus remnants, and the formation of sclerotic, circumferential ridges around the vertebral endplates. Osteoarthritic facet joints exhibited osteophytosis of the superior articular process, cartilage erosion, degeneration and buckling of the capsular ligamentum flavum, effusion, hemarthrosis, and derangement of meniscoid synovial folds. On extension and rotation there was significant encroachment on the nerve root complex and radicular vessels; the importance of the segmental blood circulation is discussed.

Computed tomography and cryomicrotomy of lumbar spine specimens. A new technique for multiplanar anatomic correlation.

To produce undistorted anatomic material accurately correlating with multiplanar computed tomograms of the lumbar spine, frozen cadaver specimens were embedded in well-defined positions and examined in a high resolution CT scanner in axial, coronal, sagittal and oblique projections and subsequently sectioned through in the same plane on a heavy-duty cryomicrotome. Photography of the slightly thawed surface of the specimens at cutting-height intervals corresponding to the feed of the scanner rendered anatomic images in natural colours and with excellent detail resolution. The accurate coincidence of the plane of cryosectioning with the plane of the computed tomography (CT) permits a detailed morphologic evaluation of CT scans in different projections.

Findings and outcome in whiplash-type neck distortions.

STUDY DESIGN: The authors assessed the clinical and imaging findings and late outcome in 50 patients with whiplash-type neck distortions (17 men, 33 women, mean age 33 years). SUMMARY OF BACKGROUND DATA: Early symptoms are neck pain, stiffness, and sometimes radiating pain; later bizarre symptomatology poses intricate clinical and medicolegal problems. Pathoanatomic studies indicate that soft tissue injuries may be overlooked. METHODS: Repeated clinical and radiographic examinations (plain and flexion-extension radiograms and contrast magnetic resonance imaging evaluated with a new grading system); surgical findings; follow-up were performed after 1 and 5 years by an independent observer neurologist. RESULTS: Neck pain persisted in 24 patients; radiating pain developed within 6 weeks in 19 patients. Two patients with segmental instability had posterior fusions and complete pain relief. Eight patients with severe radiating pain and large disc protrusions on magnetic resonance had nine surgically confirmed fresh disc herniations. Discectomy and fusion alleviated pain in these patients, whereas symptoms largely persisted in the conservatively treated patients. CONCLUSIONS: A high incidence of discoligamentous injuries was found in whiplash-type distortions. Most patients with severe persisting radiating pain had large disc protrusions on MRI that were confirmed as herniations at surgery. Neck and radiating pain were alleviated by early disc excision and fusion.

Lateral lumbar spinal canal stenosis: classification, pathologic anatomy and surgical decompression.

The lateral region of the lumbar spinal canal is subject to pathologic alterations which encroach upon the neural structures located within. In order to further understanding and facilitate communication among specialists in diverse disciplines, a subdivision of the lateral region is proposed to comprise three zones: entrance zone, mid-zone and exit zone. The anatomical boundaries of these zones are defined and the pathologic conditions of each are described, and serve as the basis for techniques of surgical decompression when clinically required.

Indirect spinal canal decompression in burst fractures treated with pedicle screw instrumentation.

STUDY DESIGN: Prospective evaluation of spinal canal areas in 67 consecutive burst fractures between T12 and L2 treated by reduction and stabilization with a pedicle fixator. OBJECTIVES: Assessment of the efficacy of "indirect" spinal canal decompression in a large series of burst fractures. SUMMARY OF BACKGROUND DATA: Up to 50% of burst fractures cause neurologic impairment. Reduction and posterior instrumentation is the most common surgical treatment. This also reduces spinal canal encroachment by indirect decompression. No consensus exists as to the consistency and adequacy of such indirect decompression. METHODS: Spinal canal areas were measured on preoperative and postoperative computed tomography scans. The degree of encroachment was compared with clinical and radiographic variables for possible correlation. RESULTS: Spinal canal encroachment was more severe among patients with neurologic deficits than among the neurologically intact. Postoperatively, mean encroachment was reduced from 35% to 12% at T12, from 37% to 17% at L1, and from 52% to 35% at L2. Loss (and postoperative restoration) of anterior vertebral height correlated best with the degree of canal encroachment (and its reduction), especially in Denis Type A burst fractures. In Denis Type B fractures, canal compromise usually was less severe and fragment reduction better in patients older than 40 years of age than in younger patients. CONCLUSIONS: Indirect decompression in burst fractures averages about half of the preexisting encroachment. Results are usually better at T12 and L1 than at L2. Additional or secondary decompression is rarely indicated if these fractures are treated early and by experienced surgeons. Burst Type B fractures in patients older versus younger than 40 years of age differ in many respects.

Anatomic and biomechanical assessment of transarticular screw fixation for atlantoaxial instability.

The purpose of this study is to elucidate anatomically the atlantoaxial transarticular screw fixation described by Magerl in 1979 and compare it biomechanically with Gallie wiring. Five human C1-C2 specimens were tested in flexion/extension and rotation intact, then after wiring and screw fixation. Mean screw length was 39 mm, 25 mm in the C2 lamina and 14 mm in the lateral mass. Angular displacement of screwed specimens was significantly less than control or wired groups. Stiffness at 0-0.5 Nm loads was significantly greater for screwed specimens than for wired or controls (101 +/- 49 Nm, 10.3 +/- 9.2 Nm, and 1.96 +/- 0.18 Nm, respectively). All specimens withstood 5 Nm in flexion and extension without failure. Screw fixation provides stability comparable to Gallie wiring and is stiffer at low-range forces and rotational angles.

Surgical anatomy of the sacrum. A guide for rational screw fixation.

Anterior sacral anatomy was studied to allow safe sacral screw placement. The study included 27 bony sacra. Intrapelvic dissections were performed. Cadaveric specimens were dissected and photographed. The position and angulation of the first sacral foramen was extremely variable. After the position of the L5 root, sacral roots, and iliac vessels, was considered, safe posterior sacral screw implantation could be assured through placement above the level of the first sacral foramen directed medially toward the promontory, parallel to the superior sacral end-plate. Complications of indiscriminate screw placement included L5-root damage, iliac vein penetration, and intractable perineal pain due to sacral root injury. Preoperative computed tomography with the scanner gantry tilted to parallel the superior sacral end-plate defined the great vessels, neural foramens, inclination of the superior sacral end-plate, and prominence of the posterior ileum. Surgical accuracy was evaluated after surgery with computed tomography.

Analysis of peridural scar formation and its prevention after lumbar laminotomy and discectomy in dogs.

STUDY DESIGN: Peridural fibrosis after lumbar laminectomy and discectomy has been implicated (not proven) as one of the factors that contribute to continuing or recurrent radicular and/or low back pain. This animal experimental study was designed to unequivocally show the stages in the development of scar tissue and to what extent, if any, scar tissue development is influenced by interposing fat grafts and Na hyaluronate of different molecular weights. METHODS: A four-level unilateral lumbar laminotomy, anular fenestration, and nucleotomy was performed in 11 dogs. In each dog, levels were selected at random: one to serve as an empty control and three to insert the following: a fat graft, a viscous (1.9%) solution of Na hyaluronate, and a 1% high molecular weight solution of Na hyaluronate solution. The animals were killed at 1 day, 2 days, and 1, 2, 4, and 12 weeks postoperatively. Immediately after the dogs were killed, the lumbar spines were frozen in situ with dry ice, the lumbar spines were harvested and sectioned with a cryomicrotome. Close-up photographs taken at submillimeter intervals at each level were digitized and postprocessed with a computer. RESULTS: In the early postoperative period a hematoma was found in the pathway of the surgical dissection. During a 2-4 week period, this hematoma was replaced by a thick, white fibrotic tissue mass. Fibrosis was markedly less pronounced at the hyaluronate levels, especially the high molecular weight subset. Two-way statistical analysis of variance without replications revealed significantly less scar formation at the 0.05 level in the hyaluronate vs. the control segments. Dunnett's test, comparing each group individually with the control, revealed no difference between the fat groups and the control subjects. There was a significant difference between 1.9% Na hyaluronate and control. CONCLUSIONS: Viscous hyaluronate solution with its semifluid properties coats the nerve roots and dura anteriorly and posteriorly and reduces peridural fibrosis in the critical anterior region where adhesions form between the nerve root and anulus fibrosus.

Three-dimensional movements of the upper cervical spine.

Knowledge of the normal movements of the occipito-atlanto-axial joint complex is important for evaluating clinical cases that may be potentially unstable. The purpose of this in vitro study was to quantitatively determine three dimensional movements of the occiput-C1 and C1-C2 joints. Ten fresh cadaveric whole cervical spine specimens (occiput to C7) were studied, using well-established techniques to document the movements in flexion, extension, left and right lateral bending, and left and right axial rotation. Pure moments of a maximum of 1.5 N-m were applied incrementally, and three-dimensional movements of the bones were recorded using stereophotogrammetry. Each moment was applied individually and in three load/unload cycles. The motion measurements were made on the third load cycle. Parameters of neutral zone, elastic zone, and range of motion were computed. Neutral zones for flexion/extension, right/left lateral bending, and right/left axial rotation were, respectively: 1.1, 1.5, and 1.6 (occiput-C1); and 3.2, 1.2, and 29.6 degrees (C1-C2). Ranges of motion for flexion, extension, lateral bending (one side), and axial rotation (one side) were, respectively: 3.5, 21.0, 5.5, and 7.2 degrees (occiput-C1 joint) and 11.5, 10.9, 6.7, and 38.9 degrees (C1-C2 joint). The greatest intervertebral motion in the spine was axial rotation at the C1-C2 joint, with the neutral zone constituting 75% of this motion.

Vertebral burst fractures: an experimental, morphologic, and radiographic study.

Spinal burst fractures are produced by rapid compressive loading, and may result in spinal cord injury from bone fragments forced from the vertebral body into the spinal canal. This fracture is one of the most difficult injuries of the spine to successfully treat, in part because the biomechanics of reduction and the exact mechanism by which the distraction forces are transmitted to the intracanal fragments of the burst fracture have not been adequately investigated. The authors developed a reproducible technique for creating these fractures in vitro. The fractures produced were identical to those observed in clinical practice, and were used for investigating the mechanics of this fracture and its reduction. This work describes the pathologic anatomy of the burst fracture both on the gross structure and also on microtome sections of the vertebrae, and examines the biomechanics of fracture reduction. The margins of the vertebral bone fragment, which was forced posteriorly into the spinal canal during fracture, were noted to extend far laterally beyond the pedicles. The authors also found extensive damage not only to the disc above the injured level, but also to that below, explaining the clinical observation that disc degeneration frequently occurs at both levels. Examination of anatomic data provided by microtome section supported the hypothesis that the fibers that actually reduce the intracanal fragment originate in the anulus of the superior vertebra in the midportion of the endplate and insert into the lateral margins of the intracanal fragment. Investigations using magnetic resonance imaging confirmed that these obliquely directed fibers account for the indirect reduction of the fragment. The authors' studies demonstrate that the posterior longitudinal ligament provides only a minor contribution in the reduction of the fracture in comparison to the attachments of the posterior portion of the anulus fibrosus. The forces required to reduce this fragment were studied. Distraction was found to be the predominant force required for indirect posterior reduction. This was confirmed by a series of tests using devices that provided segmental fixation. The application of uniform distraction forces was most effective in the posterior reduction of the intracanal fragment.

Magnetic resonance imaging as a tool for evaluation of traumatic knee injuries. Anatomical and pathoanatomical correlations.

Traumatic injury to the knee remains a diagnostic and therapeutic challenge. Magnetic resonance imaging (MRI) has been applied to musculoskeletal pathoanatomy and has been shown to be an effective tool for definition and characterization of knee pathology. A systematic approach is taken to establish anatomical and pathoanatomical correlations, as well as the role of MRI in the management of knee injuries. Imaging was performed at the UCLA Medical Center using a permanent magnet system and a combination of solenoidal surface coils and thin-section, high-resolution scanning techniques. Images depict structural anatomical and spatial details of the knee that correlate well with corresponding cadaveric cryosections. To determine pathoanatomical correlations and the efficacy of MRI, 105 patients with preoperative diagnoses of meniscal tears, anterior and posterior cruciate ligament tears, tibial plateau fracture, and patella and quadriceps injuries were imaged. Results indicated that for the medial meniscus MRI demonstrated a 95.7% sensitivity, 81.8% specificity, 90% accuracy, 88.2% positive predictive value (PPV), and 93.1% negative predictive value (NPV). Imaging of the lateral meniscus demonstrated a 75% sensitivity, 95% specificity, 91% accuracy, 80% PPV, and 94% NPV. MRI of the ACL revealed 100% sensitivity, specificity, accuracy, positive and negative predictive values. MRI is a noninvasive tool which uses no ionizing radiation and can accurately define and characterize anatomy and pathoanatomy. This study indicates that MRI in conjunction with clinical evaluation can contribute to treatment decision-making processes and assist in preoperative planning. An algorithm demonstrating the potential clinical use of MRI is presented.

Anatomy and surface geometry of the patellofemoral joint in the axial plane.

We studied the anatomy of the patellofemoral joint in the axial plane on cryosections from a cadaver knee and on MR arthrotomograms from 30 patients. The cryosections revealed differences in the geometry and anatomy of the surface of the articular cartilage and corresponding subchondral osseous contours of the patellofemoral joint. On the MR arthrotomograms the surface geometry of the cartilage matched the osseous contour of the patella in only four of the 30 knees. The articular cartilaginous surface of the intercondylar sulcus and corresponding osseous contour of the femoral trochlea matched in only seven knees. Since MR arthrotomography can distinguish between the surface geometry of the articular cartilage and subchondral osseous anatomy of the patellofemoral joint, it allows the surgeon and the radiologist to appraise the true articulating surfaces. We therefore recommend MR arthrotomography as the imaging technique of choice.

Normal anatomy of the hand and wrist.

An understanding of the anatomy is invaluable when such small structures as described here are to be evaluated. Because MR imaging reveals greater detail, radiologists are obliged to use the information available to benefit the clinician and the patient. A working knowledge of the anatomic elements and their nomenclature also engenders confidence in the imager on the part of the hand surgeon. This discussion serves as the basis for meaningful comprehension of the pathologic entities that are presented in the articles that follow.

Postoperative cervical spine specimens studied with the cryoplaning technique.

Eight cervical spine specimens from patients who had undergone anterior and/or posterior screwplate fixation for traumatic or pathologic fractures and degenerative disorders were frozen in situ during clinical autopsies after the arteries were injected with red contrast medium. After partial thawing of the specimens, the metallic implants were extracted and the screw tracts and other implant cavities were filled with blue casting medium. Sagittal high-resolution computed tomography (CT) scans of the frozen specimens were obtained and correlated with closely spaced cryosectional images at the same levels. This technique not only facilitates accurate radiologic pathoanatomic correlations, but also detailed analysis of implant positioning, adequacy of reduction and decompression, and the cause of surgical complications.

[Irreducible fracture dislocation of the cervical vertebrae. Patho-anatomical study using frozen sections]. / Irreponible Luxationsfraktur der unteren Halswirbelsäule. Eine pathologisch-anatomische Studie mit der Gefrierschneidemethode.

A young patient with tetraplegia resulting from an unstable and irreducible fracture dislocation of the lower cervical spine unexpectedly died from an intercurrent gastrointestinal hemorrhage. Following routine autopsy the whole, intact cervical spine was frozen in situ, tomographed in the lateral projection and sectioned through on a heavy duty cryomicrotome with use of a newly modified technique. Detailed analysis of 50 sections revealed, among other things, that a fragment from the lacerated intervertebral disc had become impinged between the body of a vertebra and the spinal cord constituting the hindrance to reduction. No obstacle to reduction was seen at the level of the facet joints.