A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response.

Cancer cells within a tumour have heterogeneous phenotypes and exhibit dynamic plasticity. How to evaluate such heterogeneity and its impact on outcome and drug response is still unclear. Here, we transcriptionally profile 35,276 individual cells from 32 breast cancer cell lines to yield a single cell atlas. We find high degree of heterogeneity in the expression of biomarkers. We then train a deconvolution algorithm on the atlas to determine cell line composition from bulk gene expression profiles of tumour biopsies, thus enabling cell line-based patient stratification. Finally, we link results from large-scale in vitro drug screening in cell lines to the single cell data to computationally predict drug responses starting from single-cell profiles. We find that transcriptional heterogeneity enables cells with differential drug sensitivity to co-exist in the same population. Our work provides a framework to determine tumour heterogeneity in terms of cell line composition and drug response.

Prevention of recurrent radicular pain after lumbar disc surgery: a prospective study.

BACKGROUND: Postoperative epidural fibrosis is a major causative factor of low-back pain even if microsurgical techniques are adopted to reduce this phenomenon. To prevent the recurrent radicular pain caused by this problem, we utilized adipose tissue drawn from the same patient; at the end of surgical procedure, the fat was placed around the spinal root or the dural sac. This procedure was evaluated by a prospective, randomised study. METHOD: From 180 patients operated on for lumbar discectomy between January 2000 to December 2001, 74 were enclosed in the study. In 37 patients, the spinal root was covered by autologous fat (group A), in the other 37 (control group, B), this procedure was not adopted. One year after surgery, all the patients were evaluated with clinical and radiological (Magnetic Resonance Imaging) follow-up. Only two patients were lost to follow-up. FINDINGS: 71% of the patients in group A had 100% of clinical and radiological post-operative outcome score; this result was obtained only in 35% of the patients in group B. A clinical score evaluating pain syndrome (from grade 0 to 5) and a radiological score evaluating postoperative fibrosis (from grade 0 to 4) was adopted. Therefore, group A had best outcome as compared to control group. CONCLUSIONS: The authors found a positive effect in the reconstruction of epidural fat with autograft of adipose tissue to prevent postoperative scarring and failed-back syndrome related to postoperative fibrosis.

Anterior submuscular transposition of the ulnar nerve in severe cubital tunnel syndrome. Personal experience.

AIM: The authors report the results of anterior submuscular transposition, on a clinical series of selected patients with severe cubital tunnel syndrome. In these patients, the degree of ulnar nerve compression was valued using a grading system that includes measurements of motor and sensitive function. In this series, a technique of flexor-pronator mass Z-lengthening was adopted. METHODS: From 1998 to 2002, 18 patients were surgically treated with anterior deep submuscular transposition for cubital tunnel syndrome. The preoperative status was determined using Dellon's classification. Fifteen out of 18 patients were graded as Dellon's grade 3 (severe syndrome). The mean duration of follow-up after surgery was 27.6 months. RESULTS: Postoperative outcome was assessed in all the 15 patients according to a modified Bishop scoring system. Based on this score, 6 patients (40%) were graded as excellent, 7 (47%) were graded as good and 2 (13%) were graded as fair. The complete recovery occurred about 6 months after surgery. None complication was observed. CONCLUSION: Treatment of severe cubital syndrome by means of a technique of flexor-pronator mass Z-lengthening was linked to 87% rate of good to excellent results. The present study demonstrate the feasibility of this technique with restitutio ad integrum in spite of the severity of the syndrome. None failure nor recurrence was present in this series.

Microsurgical approach to lumbar synovial cysts. Technical notes.

Intraspinal extradural synovial cysts are quite common in the lumbar spine. With respect to clinical presentation and surgical treatment, juxta-facet cysts (ganglion and synovial cysts) share identical characteristics and results. Nowadays, current treatment strategies of intraspinal juxta-facet cysts continue to inspire controversy regarding appropriate surgical approaches, and include many technical options. The purpose of this report is to illustrate the advantage of minimally invasive approaches in 3 cases of lumbar synovial cysts. We performed a small flavectomy in the 1st case, a transarticular partial facectomy, followed by etherologous bone graft fusion in the 2nd case, and a flavectomy and partial facectomy in the 3rd case. In our cases, a microsurgical approach to lumbar synovial cysts yielded to complete excision of the lesions and excellent pain relief, with early mobilization and hospital discharge of the patients. In our opinion, minimally invasive approaches and microsurgical excision of lumbar juxta-facet cysts are advantageous over conventional lumbar laminectomy because they reduce later development of segmental instability at the operative level, and therefore a less invasive strategy for intraspinal synovial cysts removal should be recommended.

Does the neuronal plasticity exist in elderly patients? report of an unusual clinical case.

STUDY DESIGN: Case report. OBJECTIVE: To report complete recovery after paraplegia in an elderly patient after removal of meningioma at C7-T1 level. SETTING: Department of Neurosurgery, Reggio Calabria, Italy. METHODS: An 82-year-old lady with 48 months of progressive weakness and numbness was admitted with complete paraplegia lasting 15 days. Investigations (magnetic resonance imaging (MRI)) demonstrated a meningioma at C7-T1. The tumour compressed the extremely thinned spinal cord. MRI after surgery showed no evidence of residual tumour and the spinal cord was of normal dimensions. The patient recovered fully and locomotion was restored. CONCLUSION: Surgical decompression gave an excellent result. The result raises the possibility of neuronal plasticity.

"Approaches and surgical results in the treatment of ventral thoracic meningiomas. Review of our experience with a postero-lateral combined transpedicular-transarticular approach.".

BACKGROUND: The surgical treatment of anterior thoracic meningiomas provides a set of technical difficulties: the access is obstructed by the spinal cord posteriorly, thoracic cage and musculature laterally, mediastinum and pleural cavity anteriorly. It is fundamental to avoid any manipulation of the compressed, but also undamaged spinal cord: this shows significant plastic capabilities. Any effort should be directed to maximizing the contribution of the plasticity in order to obtain a good functional recovery. METHOD: We have utilized a postero-lateral combined transpedicular-transarticular approach in order to obtain less invasiveness on the neural structures. Ten patients with ventral thoracic meningioma were operated in the last 5 years. The preoperative clinical evaluation, follow-up monitoring, timing of recovery, Clinical/Functional Grade change were analysed. FINDINGS: 8 Patients had significant neurological improvement, 2 were unchanged. Magnetic Resonance Imaging (MRI) was useful in preoperative planning. Radical excision was possible in all patients and the late postoperative MRI did not reveal recurrence of the lesions at this time. To date, there has been no evidence of clinical or radiological instability. INTERPRETATION: We found this surgical exposure very helpful in the treatment of anterior thoracic meningiomas. The related morbidity and risk of instability are minimal. The combined postero-lateral approach offers a good surgical access to ventral, lateral and dorsal aspects of the thoracic spinal canal without manipulation of the spinal cord. Exposure is obtained by avoiding damage to the pleura and manipulation of the lungs and mediastinum and may be a feasible alternative in elderly patients, too.

Clinical evaluation of thallium-201 single photon emission computed tomography in equivocal neuroradiological supratentorial lesions.

BACKGROUND: We performed cerebral 201Tl SPECT study on 38 presurgical patients with equivocal neuroradiological supratentorial lesions to detect differences in 201Tl uptake index between tumor/non-tumor and high-grade/low-grade samples. METHODS: Authors identified 38 cases with presurgical equivocal neuroradiological supratentorial mass lesions. All cases were submitted to histological confirmation of the lesion by biopsy, sub-total or gross-total removal of the tumor. Between 23 patients suffering from gliomas, 13 were histologically classified as being of low-grade malignant tumors and 10 were classified as being of high-grade malignancy. Fifteen non-tumor histopathological specimens were also detected. The 201Tl index was defined as the ratio of average counts per pixel in the lesion to these in the opposite region. Analysis of variance (ANOVA) and unpaired Student's OtO-test statistical methods were applied. Actuarial survival time from the date of diagnosis was calculated using the Kaplan-Meier method. Follow-up evaluation and survival time were obtained through referring physicians. Cerebral CT or MR images were obtained every three months after discharged, or more often if indicated. RESULTS: Results showed that the 201Tl uptake index ranged from 1.10 to 3.00 in the tumors lesions (mean+/-SD: 1.68+/-0.51) and from 0.80 to 1.40 in the non-tumors lesions (mean+/-SD: 1.07+/-0.17), (alpha < 0.0006 percent;). The 201Tl uptake index ranged from 1.10 to 2.30 in 13 patients with low-grade tumors (mean+/-SD: 1.45+/-0.34) and from 1.30 to 3.00 in 10 patients with high-grade tumors (mean+/-SD: 1.98+/-0.55), (alpha < 0.5 percent;). CONCLUSIONS: Our results demonstrate the clinical utility of 201Tl brain SPECT to differentiate equivocal neuroradiological supratentorial lesions and to correlate relationship between preoperative diagnosis, histological tumor grade and prognosis.

Neuroendoscopic approach to complex hydrocephalus. Personal experience and preliminary report.

BACKGROUND: Neuroendoscopic premammilary third-ventriculocisternostomy in non-communicating hydrocephalus represents, to date, the less invasive and effective procedure, whereas the neuroendoscopic approach to complex-hydrocephalus is limited to several small anecdotal series. METHODS: Among 57 pediatric patients affected by obstructive hydrocephalus, ranging in age from prenatal diagnosis to 3 years (mean 1.2 year+/-11 months) and recruited over a 2-year period, we identified 11 cases with presurgical neuroradiological complex-hydrocephalus, at admission to our Department. In two cases Magnetic Resonance imaging showed bilateral atresic foramen of Monro and corpus callosum agenesya. In these cases an extracranial cerebrospinal fluid shunt device was implanted. The authors report retrospectively, the personal experience on a series of 9 pediatric patients with complex-hydrocephalus, such as multishunted (4 cases), multiloculated hydrocephalus (3 cases), and multiple ventricular cysts plus hydrocephalus (2 cases), in which a neuroendoscopic approach was performed. At admission, symptoms and signs of an increased intracranial pressure were presents in all cases. Follow-up ranged from 3 months to 2 years. In 8 cases third ventriculostomy was successfully performed whereas, in one case, the endoscopic procedure, in a patient younger than 1 month, was aborted and an extracranial cerebrospinal fluid device was implanted. RESULTS: In the postoperative period and during follow-up, a symptomatic relief and clinical improvement of preoperative signs and symptoms of increased intracranial pressure was seen in all cases. Nevertheless, in two patients psychomotor retardation worsened, respectively 6 and 7 months after the endoscopic procedure and then, an additional extracranial cerebrospinal fluid shunt device was implanted. CONCLUSIONS: In our selected cases of complex-hydrocephalus, the neuroendoscopic approach did not fail to determine clinical improvement after the first procedure, in spite of increased technical difficulties and minimum decreases of ventricular volume in postoperative images.

Unusual clincal presentation of cerebral-isolated sarcoidosis. Case report and review of the literature.

The authors report the case of a 31-year-old man, who presented an hemorrhagic onset of a cerebral-isolated sarcoidosis, to date never described in the literature. Unusual clinical manifestation, neuroradiological study and direct histological confirmation are presented. Moreover, Gallium-67 Single Photon Emission Computed Tomography (Ga-67 SPECT) contribution is indicated to complete the evaluation of patients with cerebral inflammatory lesions, such as neurosarcoidosis, and in cases of equivocal neuroradiological imaging, to evaluate uptake activity of the inflammatory tissue. The patient did well and reported no further progression of his disease during 7 months of follow-up.

High-dose heparin plus warfarin administration in non-traumatic dural sinuses thrombosis. A clinical and neuroradiological study.

BACKGROUND: The management of intracranial dural sinuses thrombosis is still controversial and uncertain. The authors report the cases of 7 patients with non-traumatic thrombosis of the dural sinuses and describe the most important radiographic findings, the indication, effectiveness of antithrombotic therapy, and outcome. METHODS: A retrospective review was conducted of 7 cases of dural sinus thrombosis admitted, between 1994 and 1996, to our division. All patients underwent full anticoagulation therapy. Heparin was administered, using a dose of 25,000 units/day for two weeks; warfarin was given using a dose of 5 mg twice daily. Treatment course was followed by maintenance treatment with a single administration of 5 mg/day of warfarin. All patients were submitted to close titration and coagulation profile monitoring. RESULTS: In 4 cases Magnetic Resonance Imaging-Angiography (Angio-MRI) was performed for following up the recanalization of the sinuses, resulting a persistent no patency of the dural sinuses. Three patients underwent contrast-enhanced CT scan, demonstrated an "empty delta sign" in the sagittal sinus, confirming no recanalization. Nevertheless, six patients had have a good quality recovery, and one patient a moderate disability. DISCUSSION: Cerebral venous sinus thrombosis is an uncommon cause of cerebral infarction, and may be mistaken, unless specifically sought. The natural history of the disease is highly variable, with a mortality rates range from 10% to 20%. At present, in our opinion, the venous phase of Angio-MRI is the definitive examination, and a gold standard for diagnosis of dural sinus thrombosis. In our cases, antithrombotic therapy has been found to be a safe and effective treatment, despite contrast-CT scans and Angio-MRI showed no recanalization of the sinuses, in all patients.

Intracranial pressure, cerebral perfusion pressure, and SPECT in the management of patients with SAH Hunt and Hess grades I-II.

The objective of our study was to examine the course of intracranial pressure (ICP) in patients with SAH Hunt and Hess grades I-II and to analyze the relationship between ICP, cerebral perfusion pressure (CPP) and cerebral blood flow (CBF). Twenty-three patients were studied. ICP, arterial blood pressure (ABP) and CPP were continuously recorded. The measurements of CBF with single-photon emission computed tomography (SPECT) were performed in fifteen patients, who showed TCD flow velocities exceeding 120 cnlJsec. In the first two days after SAH four patients (15%) showed a normal ICP, six (25%) patients had a moderate increase of ICP ranged from 15 to 25 mm Hg and thirteen (60%) patients had ICP values higher than 25 mm Hg. Seven of these patients, with ICP values higher than 40 mm Hg, showed clinical signs of delayed ischaemia. After the treatment with osmotic diuretic, ICP decreased and a clinical improvement was observed with the exception of one patient. In this patient, the SPECT study showed middle cerebral hypoperfusion concordant with the clinically ischaemic hemisphere. Our study showed the utility of the monitoring of these parameters in patients with lower grade SAH, because it allows the modulation of the therapeutic approach and defines the onset of neurological deficits secondary to cerebral ischaemia in all grades of SAH.

Transverse microincisions of the outer layer of the dura mater combined with foramen magnum decompression as treatment for syringomyelia with Chiari I malformation.

Numerous surgical procedures have been proposed for treatment of syringomyelia associated with Chiari I malformation, but the optimal treatment has not yet been uniformly standardised. The main aim of the surgical treatment of syringomyelia/Chiari I complex is directed toward restoration of physiological cerebrospinal fluid dynamic at the craniovertebral junction. We report the surgical results of eight patients, affected by syringomyelia and Chiari I malformation, age range from 18 to 62 years, treated by bony foramen magnum decompression combined with transverse microincisions of the outer layer of the dura mater. In an average postoperative follow-up period of two years neurological symptoms and signs improved in seven patients. Postoperative Magnetic Resonance showed a decrease in size of the syrinx in seven patients. These results suggest that foramen magnum decompression combined with transverse microincisions of the outer layer of the dura 1) is an effective and safe treatment option for syringomyelia and Chiari I malformation, 2) corrects the circulatory disturbances of cerebrospinal fluid dynamic, 3) leads to a decrease in size of the syrinx and to a significant improvement in neurological signs and symptoms, 4) avoids complications of intradural approaches and syringosubarachnoid shunting.

Experimental incomplete spinal cord injury: treatment with a combination of nimodipine and adrenaline.

The effect of combination of nimodopine and adrenaline treatment on the motility deficits following secondary spinal cord damage was studied. Morphometric axonal analyses were also done. Incomplete spinal compression was induced in albino New Zealand rabbits anesthetized with ketamine. Neurological deficit was assessed by Tarlov's scale. The animals were divided into different groups. In one group the animals were anesthetized and subjected to all procedures except spinal cord injury and pharmacological treatment. Each of the other groups were divided into 2 subgroups; the spinal cord compression was induced for 2 min in one subgroup and 5 min in other subgroup. The pharmacological treatment in different groups consisted of slow intravenous infusions of saline alone, combination of adrenaline and nimodipine, nimodipine alone and adrenaline alone. The evolution of the motor damage was evaluated by comparing scores obtained with Tarlov's scale 1, 24 and 48 hrs after the end of spinal cord compression. In all animals, spinal cord compression for 2 and 5 min induced a 5th degree motor deficit. Treatment with saline improved slightly the motor deficit. The improvement of motor deficit was much better when a combination of nimodipine and adrenaline was used. The animals treated with nimodipine alone showed a better recovery in comparison with the animals treated with saline alone.

Intracranial pressure monitoring in children: comparison of external ventricular device with the fiberoptic system.

Several intracranial pressure monitoring devices have been developed in the past several years. We have recently adopted the Camino fiberoptic device that permits subdural, intraparenchymal, and intraventricular monitoring. In this report we compare experiences in monitoring a group of pediatric patients with severe craniocerebral trauma and coma, grouped according to severity of Glasgow Coma Scale score. Patient age ranged from 2 to 16 years. Twelve patients were monitored by a ventricular catheter and 37, treated more recently, by a Camino fiberoptic device. The study demonstrated that the fiberoptic device and the ventricular catheter have the same accuracy and reliability. The fiberoptic method correlates very closely with the ventriculostomy method, but the pressure values are always 3 +/- 2 mmHg lower than those obtained with the conventional pressure transducer system, especially in more critically ill patients. This new technique is also easier to implant, safer to use, has minimal drift, and is minimally invasive, which particularly speaks for its use in pediatric patients.

Monitoring of brain tissue pressure with a fiberoptic device.

Continuous monitoring of brain tissue pressure can now be achieved with intracerebral placement of fiberoptic microtransducers. This study was undertaken to test the safety, accuracy, and reliability of this relatively new type of intracranial pressure (ICP) monitoring. Initially, the fiberoptic device was compared with a concurrently functioning intraventricular catheter in 18 patients. The results from the two methods corresponded closely over a wide range of pressures, and the correlation coefficient approached 1.0. Subsequently, this monitor was used for routine measurement of ICP in a series of almost 200 neurosurgical patients at risk of intracranial hypertension. The tracings showed good wave forms and consistent absolute values of ICP. No instances of hemorrhage, mechanical failure, or other complications were associated with this monitor, except one case of infection, which was not directly attributable to the device per se. When bilateral intraparenchymal pressures were recorded in patients with unilateral mass lesions, significant transitory pressure differentials between the ipsilateral and contralateral sides were documented. It is concluded that monitoring intraparenchymal pressure with the fiberoptic device offers safe and reliable ICP recordings for routine neurosurgical practice. In patients with unilateral masses, ICP should be measured in close proximity to the lesion.

[Prevention of postoperative complications in vertebro-spinal cord pathology]. / Prevenzione delle complicanze post-operatorie nelle patologie vertebro-midollari.

In 352 patients, affected by vertebral-medullary pathology, we evaluated the role played by the prevention or by the treatment of postoperative complications. We also evaluated their influence on the clinical outcome and neurological recovery. In every case we recorded a scrupulous post-operative neurological monitoring of the eventual complications, on the basis of the type, gravity and duration. From our results it appears that the complications, mostly secondary to infectious diseases, have an influence on the clinical and neurological recovery. We highlight the importance of an adequate nutritive management to prevent the complications, specifically those secondary to infectious diseases and cutaneous lesions.

Clinical, morphometric and ultrastructural aspects in a new model of spinal cord compression.

A new model of spinal cord compression is presented. Forty-two New Zealand albino rabbits weighing between 1.2 and 1.5 kg were submitted to spinal cord compression to about half of its normal diameter by vascular Sugita's clip to different compression time (sham, 5-10-20 minutes e 1-6-12 hours) and sacrified after 72 hours. The consequent neurological dysfunction size of lesion was graded by Tarlov's scale for voluntar motility. Ultrastructural and morphometrical studies were carried out to evaluate changes in shape, perimeters, axonal and myelin areas of the lateral and the posterior tract of spinal cord. A 10 minute decrease of 50% of the transverse diameter of the spinal cord causes a defined damage. The swelling of myelin is a useful index of the importance of the damage.

Brain metastases: surgical versus conservative treatment.

A comparative study on surgical versus conservative brain metastases treatment has been carried out. Patients have been divided in seven groups by means of treatment modalities. Follow-up, has been carried out taking into consideration mean survival time and quality life in particular, evaluated by means of Order's classes. Anaesthesiological management problems were discussed also. From data analysis, it follows that untreated patients, (group 1) had a lower mean survival time than that of the other patients. Thirty days after first evaluation, 85% of these patients had a very poor quality life. Patients who underwent surgery associated to radio and chemotherapy (group 2) have had better recovery of functional autonomy and longest mean survival time. Among these, thirty days after treatment only 3% had a very poor quality life, while 67% had the better quality life. Patients who underwent others treatment modalities had intermediate results.