T cell memory,anergy and immunotherapy in breast cancer

T cell immunity in breast cancer is suggested to play a role in tumor dormancy, a period of stability which can correspond to the time interval between primary treatment and tumor recurrence. Bone marrow in breast cancer patients seems to be particularly important because it is highly enriched with cancer specific memory T cells. Similar cells can be found in peripheral blood, but these appear to be functionally anergic. The immune system of primary operated breast cancer patients does not seem to be completely anergized. Bone marrow derived memory T cells can be reactivated ex vivo and show functional reactivity, including tumor rejection in NOD/SCID mice. Promising results were obtained from a postoperative phase-II active specific immunotherapy study. In this study, 32 patients treated with an optimal formulation of a virus-modified autologous tumor vaccine (ATV-NDV) appeared to have a significant 5-year survival benefit. Our results suggest that cancer reactive memory T cells which are enriched in the bone marrow of breast cancer patients, can be activated ex vivo via autologous dendritic cells pulsed with breast cancer tumor antigens, or they can be activated in situ via a tumor vaccine, which combines tumor antigens with virus infection. The findings should encourage further studies in breast cancer on active specific immunotherapy with tumor vaccines or adoptive immunotherapy with activated memory T cells.     

Malfunction of a Heimlich flutter valve causing tension pneumothorax: case report of a rare complication

Background  

Thoracic injuries play an important role in major trauma patients due to their high incidence and critical relevance. A serious consequence of thoracic trauma is pneumothorax, a condition that quickly can become life-threatening and requires immediate treatment.     

Clinical management of petroclival meningiomas and the eternal quest for preservation of quality of life

Background

Within the realm of neurosurgery, petroclival meningiomas are regarded as probably the most difficult tumour to be treated by microsurgery. This is due to the not infrequently large size of the tumours which, although predominantly located in the posterior fossa, may occupy more than one cranial compartment, with often significant space-occupying effect and brain stem compression. Frequent tight brain stem adherence as well as encasement of the basilar artery, its perforators and cranial nerves adds to the sometimes extreme difficulties of surgical tumour removal. Counselling patients as well as pre- and intraoperative decision making in petroclival meningiomas is even more difficult because upon clinical and radiological tumour detection, despite sometimes surprisingly large tumours, clinical symptoms are often only mild. Summarising the complicated development of petroclival meningioma surgery over the last 60 years, this paper represents the conceptual thinking of the author in regard to the treatment of petroclival meningiomas which has evolved over more than two decades, based on a special interest in these treacherous tumours, and accumulated experiences in the treatment of over 150 patients. Surgical concepts and the operative decision-making process are demonstrated in four illustrative cases.

Methods

Over a period of slightly over 20 years, between January 1988 and December 2008, 161 patients with petroclival meningiomas were managed clinically by the author or under his direct surveillance in four academic neurosurgical institutions. The observation period ranged from 4 to 242 months. Thirteen patients were lost to follow-up so, all together, complete data were available for 148 patients. In 119 patients (80%), the tumour was large. Giant tumours accounted for 7% and 11 patients, medium-sized tumours were found in 12 patients (8%) and small tumours in only six patients (4%). Sixty-two percent of the patients had invasion of Meckel’s cave or some part of the cavernous sinus, mainly the posterior region to different degrees. All giant tumours and one third of the large tumours extended into more than one cranial fossa.

Results

The treatment modalities in the 148 patients were as follows: microsurgery alone was performed in 71 patients (48%), microsurgery and adjuvant radiosurgery in 22 patients (15%) so in 93 patients (63%), altogether, microsurgery was the primary treatment. Twenty-nine patients (20%) underwent radiosurgery as their only treatment, and two patients (1%), during the very early phase of the study period, received radiotherapy. Twenty-four patients (16%) were only observed without any additional therapy. Gross total resection was achieved in 34 patients (37%), and subtotal resection, defined as removal of more than 90% of the tumour volume, was performed in another 36 patients (39%). Radical tumour removal was possible in 76% of the patients. There was no procedure-related death within 3 months post-surgery; the early post-op surgical complication rate was 31% with new neurological deficits or worsening of pre-existing deficits. During the observation period, almost all patients recovered significantly bringing the percentage of permanent neurological deficits, again mainly cranial nerve deficits, down to 22%.

Conclusions

Based on the experiences of the author, the following treatment principles in petroclival meningiomas are proposed: small tumours in asymptomatic patients should be observed. If tumour growth is detected on serial magnetic resonance imaging or treatment is desired by the patient, surgery should be the first choice. Radiosurgery in growing small tumours should be reserved to patients with advanced age or significant co-morbidities. In medium-sized tumours and symptomatic patients, radical surgery should be attempted, if possible by judicious intraoperative judgement. In large and giant petroclival meningiomas, tumour resection as radical as possible judged intraoperatively with decompression of neural structures should be performed, followed by observation and, in the case of growing tumour remnants, radiosurgery. Thus, by a combined application of advanced microsurgical techniques, thoughtful, intraoperative decision making with limited surgical aggressively and, in selected patients, with small tumours or small tumour remnants simple observation or alternative or adjunct radiosurgery, excellent results as measured by tumour control and preservation of quality of life can be achieved.     

CD4+CD25+FoxP3+ T lymphocytes fail to suppress myelin basic protein-induced proliferation in patients with multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder directed against self antigens of the central nervous system. CD4⁺CD25⁺FoxP3⁺ regulatory T cell (T_reg) mediated suppression is an essential mechanism of self-tolerance. We studied whether changes in the suppressive function of a mixture of CD25^high and CD25^intemediate expressing T_reg cells in myelin basic protein (MBP)-induced proliferation occurred in untreated MS patients. Suppression of MBP-induced proliferation was observed in 13 out of 29 (45%) MS patients; this was significantly (p < 0.05) less compared with 17 out of 19 (89%) healthy individuals. Relative T_reg counts was significantly increased in MS patients (mean ± S.D.; 20 ± 8%) compared with healthy individuals (15 ± 5%). These findings suggest that impaired T_reg function may be involved in pathogenesis of MS.     

Recovery from a spinal cord injury: significance of compensation, neural plasticity, and repair

Clinical recovery after a lesion of the central nervous system (CNS) can be attributed to mechanisms of functional compensation, neural plasticity, and/or repair. The relative impact of each of these mechanisms after a human spinal cord injury (SCI) has been explored in a prospective European multi-center study in 460 acute traumatic SCI subjects. Functional (activities of daily living and ambulatory capacity), neurological (sensory-motor deficits), and spinal conductivity (motor- and somato-sensory evoked potentials) measures were repeatedly followed over 12 months. In accordance with previous studies, complete SCI subjects (cSCI; n = 217) improved in activities of daily living unrelated to changes of the neurological condition, while incomplete SCI subjects (iSCI; n = 243) showed a greater functional and neurological recovery. The functional recovery in iSCI subjects was not related to an improvement of spinal conductivity, as reflected in unchanged latencies of the evoked potentials. This is in line with animal studies, where spinal conductivity of damaged spinal tracts has been reported to remain unchanged. These findings support the assumption that functional recovery occurs by compensation, especially in cSCI and by neural plasticity leading to a greater improvement in iSCI. Relevant repair of damaged spinal pathways does not take place.     

Microsurgical management of spinal schwannomas: evaluation of 128 cases

OBJECT: The authors conducted a study to evaluate the clinical characteristics and surgical outcomes in patients with spinal schwannomas and without neurofibromatosis (NF). METHODS: The data obtained in 128 patients who underwent resection of spinal schwannomas were analyzed. All cases with neurofibromas and those with a known diagnosis of NF Type 1 or 2 were excluded. Karnofsky Performance Scale (KPS) scores were used to compare patient outcomes when examining the anatomical location and spinal level of the tumor. The neurological outcome was further assessed using the Medical Research Council (MRC) muscle testing scale. RESULTS: Altogether, 131 schwannomas were treated in 128 patients (76 males and 52 females; mean age 47.7 years). The peak prevalence is seen between the 3rd and 6th decades. Pain was the most common presenting symptom. Gross-total resection was achieved in 127 (97.0%) of the 131 lesions. The nerve root had to be sacrificed in 34 cases and resulted in minor sensory deficits in 16 patients (12.5%) and slight motor weakness (MRC Grade 3/5) in 3 (2.3%). The KPS scores and MRC grades were significantly higher at the time of last follow-up in all patient groups (p = 0.001 and p = 0.005, respectively). CONCLUSIONS: Spinal schwannomas may occur at any level of the spinal axis and are most commonly intradural. The most frequent clinical presentation is pain. Most spinal schwannomas in non-NF cases can be resected totally without or with minor postoperative deficits. Preoperative autonomic dysfunction does not improve significantly after surgical management.     

Biomechanical comparison of occipitoatlantal screw fixation techniques

OBJECT: The stability provided by 3 occipitoatlantal fixation techniques (occiput [Oc]-C1 transarticular screws, occipital keel screws rigidly interconnected with C-1 lateral mass screws, and suboccipital/sublaminar wired contoured rod) were compared. METHODS: Seven human cadaveric specimens received transarticular screws and 7 received occipital keel-C1 lateral mass screws. All specimens later underwent contoured rod fixation. All conditions were studied with and without placement of a structural graft wired between the skull base and C-1 lamina. Specimens were loaded quasistatically using pure moments to induce flexion, extension, lateral bending, and axial rotation while recording segmental motion optoelectronically. Flexibility was measured immediately postoperatively and after 10,000 cycles of fatigue. RESULTS: Application of Oc-C1 transarticular screws, with a wired graft, reduced the mean range of motion (ROM) to 3% of normal. Occipital keel-C1 lateral mass screws (also with graft) offered less stability than transarticular screws during extension and lateral bending (p < 0.02), reducing ROM to 17% of normal. The wired contoured rod reduced motion to 31% of normal, providing significantly less stability than either screw fixation technique. Fatigue increased motion in constructs fitted with transarticular screws, keel screws/lateral mass screw constructs, and contoured wired rods, by means of 19, 5, and 26%, respectively. In all constructs, adding a structural graft significantly improved stability, but the extent depended on the loading direction. CONCLUSIONS: Assuming the presence of mild C1-2 instability, Oc-C1 transarticular screws and occipital keel-C1 lateral mass screws are approximately equivalent in performance for occipitoatlantal stabilization in promoting fusion. A posteriorly wired contoured rod is less likely to provide a good fusion environment because of less stabilizing potential and a greater likelihood of loosening with fatigue.     

Management in patients with liver cirrhosis and an umbilical hernia

BACKGROUND: Optimal management in patients with umbilical hernias and liver cirrhosis with ascites is still under debate. The objective of this study was to compare the outcome in our series of operative versus conservative treatment of these patients. METHODS: In the period between 1990 and 2004, 34 patients with an umbilical hernia combined with liver cirrhosis and ascites were identified from our hospital database. In 17 patients, treatment consisted of elective hernia repair, and 13 were managed conservatively. Four patients underwent hernia repair during liver transplantation. RESULTS: Elective hernia repair was successful without complications and recurrence in 12 out of 17 patients. Complications occurred in 3 of these 17 patients, consisting of wound-related problems and recurrence in 4 out 17. Success rate of the initial conservative management was only 23%; hospital admittance for incarcerations occurred in 10 of 13 patients, of which 6 required hernia repair in an emergency setting. Two patients of the initially conservative managed group died from complications of the umbilical hernia. In the 4 patients that underwent hernia correction during liver transplantation, no complications occurred and 1 patient had a recurrence. CONCLUSIONS: Conservative management of umbilical hernias in patients with liver cirrhosis and ascites leads to a high rate of incarcerations with subsequent hernia repair in an emergency setting, whereas elective repair can be performed with less morbidity and is therefore advocated.     

The frequency and clinical significance of congenital defects of the posterior and anterior arch of the atlas

OBJECT: In this study the authors investigated the anatomical, clinical, and imaging features as well as incidence of congenital defects of the C-1 arch. METHODS: The records of 1104 patients who presented with various medical problems during the time between January 2006 and December 2006 were reviewed retrospectively. The craniocervical computed tomography (CT) scans obtained in these patients were evaluated to define the incidence of congenital defects of the posterior arch of C-1. In addition, 166 dried C-1 specimens and 84 fresh human cadaveric cervical spine segments were evaluated for anomalies of the C-1 arch. RESULTS: Altogether, 40 anomalies (2.95%) were found in 1354 evaluated cases. Of the 1104 patients in whom CT scans were acquired, 37 (3.35%) had congenital defects of the posterior arch of the atlas. The incidence of each anomaly was as follows: Type A, 29 (2.6%); Type B, six (0.54%); and Type E, two (0.18%). There were no Type C or D defects. One patient (0.09%) had an anterior arch cleft. None of the reviewed patients had neurological deficits or required surgical intervention for their anomalies. Three cases of Type A posterior arch anomalies were present in the cadaveric specimens. CONCLUSIONS: Most congenital anomalies of the atlantal arch are found incidentally in asymptomatic patients. Congenital defects of the posterior arch are more common than defects of the anterior arch.