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.     

Acute paranoid psychosis as sole clinical presentation of hepatic artery thrombosis after living donor liver transplantation

Background  

Hepatic artery thrombosis is a devastating complication after orthotopic liver transplantation often requiring revascularization or re-transplantation. It is associated with considerably increased morbidity and mortality. Acute cognitive dysfunction such as delirium or acute psychosis may occur after major surgery and may be associated with the advent of surgical complications.     

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.     

Virtual placement of posterior C1-C2 transarticular screw fixation

We wanted to evaluate how often safe and effective posterior C1-C2 transarticular screw placement is realizable when it is performed according to guidelines given in the literature. In 50 adult patients, computerized tomography scan data from C0 to C3 were transformed into a 3D spine model. Virtually, bilateral screws were placed from the medial third of the C2-C3 facet joint towards the rim of the C1 anterior arc parallel to midline. Three categories of virtual screw position were rated: optimal (virtual screw inside the C2 pars interarticularis, transversing the middle third of the atlantoaxial joint, and sparing the vertebral artery canal), suboptimal (virtual screw violating the C2 pars interarticularis, and/or transversing the lower or upper third of the C1-C2 joint, and sparing vertebral artery canal), and unacceptable (virtual screw breaching the vertebral artery canal). Optimal placement was seen in 74, suboptimal placement in 11, and unacceptable locations in 15 sites. We conclude that due to the variability of the anatomy of the upper cervical spine, optimal transarticular C1-C2 screw placement is not possible in up to 26%, and even hazardous in up to 15%. This paper was presented in part at the Jahrestagung der Deutschen Gesellschaft für Neurochirurgie, May 25–28, 2003, Saarbrücken, Germany     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

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.     

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.     

Causes of secondary glaucoma in Paraguay

Summary Glaucoma is the third-most-frequent cause of blindness in the world, with a total of 5.2 million blind people as a result of this disease; 80 % live in developing countries. In Paraguay, after cataract it is the second-most-frequent-cause. Early detection of the risk factors and groups can help to avoid progress of this disease. Trauma, cataract and infectious uveitis represent special risks for developing secondary glaucoma, which is a more frequent cause of blindness in third-world countries than in industrialized nations. Until now there has been little data regarding the causes, disease course, and options for therapy. Therefore, secondary glaucoma was examined in Paraguay to obtain information on the situation in Latin America. The aim of the study was to explore the causes of secondary glaucoma for programs concerning prevention and therapy. From November 1996 to February 1997 patients with secondary glaucoma were examined at the University Hospital of Asunción, Paraguay. After the clinical examination the secondary glaucomas were classified. Patients with primary glaucoma were included in the same period of time as well in order to get the rate of secondary glaucoma. Altogether 293 patients were examined: 61 with secondary and 232 with primary glaucoma. The causes of secondary glaucoma in 73 eyes were: 20 (27 %) with pseudoexfoliation glaucoma, 19 (26 %) with post-traumatic glaucoma, 16 (22 %) with neovascular glaucoma, 4 (5 %) with lens-related glaucoma, 3 (4 %) with glaucoma associated with ocular surgery, 2 (3 %) with pigmentary and 2 (3 %) with corticoid-induced glaucoma. A ratio of 4:1 primary glaucomas to secondary glaucomas was found. The development of special measures for prevention and early therapy is only possible if the causes of this severe disease are explored. The results of this study represent basic information and could help to introduce of prevention programs.      

Acute hypopyon uveitis in a patient with acquired immunodeficiency syndrome treated for systemic Mycobacterium avium complex (MAC) infection with rifabutin

Background: Hypopyon-uveitis has been identified as a dosage-dependent side effect in patients with acquired immunodeficiency syndrome who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. Patients and methods: We report a 38-year-old female AIDS patient with bilateral hypopyon uveitis under therapy with rifabutin in combination with clarithromycin and indinavir. Results: At the time of presentation of the bilateral hypopyon uveitis the patient was treated with rifabutin (300 mg/day), clarithromycin (1000 mg/day) and ethambutol (1000 mg/day) for an M. avium complex infection. Also, the patient received the protease inhibitor indinavir. The rifabutin dose was reduced to 150 mg/day. Hypopyon and inflammation resolved under therapy with steroids. Conclusions: The concomitant use of rifabutin, clarithromycin, and protease inhibitors may lead to hypopyon uveitis. Reduction of dosage of rifabutin (150 mg/day) and treatment with topical steroids are required.