A mathematical model of tumour & blood pHe regulation: The HCO-3/CO2 buffering system

Malignant tumours are characterised by a low, acidic extracellular pH (pHe) which facilitates invasion and metastasis. Previous research has proposed the potential benefits of manipulating systemic pHe, and recent experiments have highlighted the potential for buffer therapy to raise tumour pHe, prevent metastases, and prolong survival in laboratory mice. To examine the physiological regulation of tumour buffering and investigate how perturbations of the buffering system (via metabolic/respiratory disorders or changes in parameters) can alter tumour and blood pHe, we develop a simple compartmentalised ordinary differential equation model of pHe regulation by the View the MathML source buffering system. An approximate analytical solution is constructed and used to carry out a sensitivity analysis, where we identify key parameters that regulate tumour pHe in both humans and mice. From this analysis, we suggest promising alternative and combination therapies, and identify specific patient groups which may show an enhanced response to buffer therapy. In addition, numerical simulations are performed, validating the model against well-known metabolic/respiratory disorders and predicting how these disorders could change tumour pHe

Proliferation and aneusomy predict survival of young patients with astrocytoma grade II

The clinical course of astrocytoma grade II (AII) is highly variable and not reflected by histological characteristics. As one of the best prognostic factors, higher age identifies rapid progressive A II. For patients over 35 years of age, an aggressive treatment is normally propagated. For patients under 35 years, there is no clear guidance for treatment choices, and therefore also the necessity of histopathological diagnosis is often questioned. We studied the additional prognostic value of the proliferation index and the detection of genetic aberrations for patients with A II. The tumour samples were obtained by stereotactic biopsy or tumour resection and divided into two age groups, that is 18–34 years (n=19) and 35 years (n=28). Factors tested included the proliferation (Ki-67) index, and numerical aberrations for chromosomes 1, 7, and 10, as detected by in situ hybridisation (ISH). The results show that age is a prognostic indicator when studied in the total patient group, with patients above 35 years showing a relatively poor prognosis. Increased proliferation index in the presence of aneusomy appears to identify a subgroup of patients with poor prognosis more accurately than predicted by proliferation index alone. We conclude that histologically classified cases of A II comprise a heterogeneous group of tumours with different biological and genetic constitution, which exhibit a highly variable clinical course. Immunostaining for Ki-67 in combination with the detection of aneusomy by ISH allows the identification of a subgroup of patients with rapidly progressive A II. This is an extra argument not to defer stereotactic biopsy in young patients with radiological suspicion of A II

Brain tumors in the mesial temporal lobe: long-term oncological outcome

Object. Surgical treatment of brain tumors in the mesial temporal lobe (MTL) is a highly demanding procedure. Only a few studies describing the surgery of MTL tumors have been reported, and they have been focused on the operative techniques and immediate results of the surgery. The authors have analyzed the long-term oncological outcome in patients with MTL tumors. Methods. Thirty-six patients with an MTL tumor were studied. The mean patient age at surgery was 32 years (range 13-62 years). The tumors were confined to the MTL (Schramm Type A) in 25 patients (69%). Extension of the tumor into the fusiform gyrus (Schramm Type C) and temporal stem (Schramm Type D) was observed in 4 and 7 patients (11 and 19%),respectively. There was a significant difference in the tumor size according to Schramm types (p = 0.001). Complete tumor resection was achieved in 26 patients (72%). All tumors were low-grade lesions except for 1 anaplastic astrocytoma. Results. After a median follow-up period of 50.5 months, 7 patients showed progression of the disease. The actuarial progression-free survival rates were 97% in the 1st year, 84% in the 2nd year, and 80% in the 5th year. The degree of tumor resection was significantly related to the tumor control failure (p = 50 years (p = 0.007, RR 8.312); and 4) short duration of epilepsy (< 6 months; p = 0.001, RR 21.54). Conclusions. Surgery is the principal treatment for MTL tumors, despite its technical difficulty. Complete tumor resection is strongly recommended for long-term tumor control. The MTL tumors are heterogeneous in their prognosis. Older age, short duration of epilepsy, and tumor size are all associated with poor outcome. Patients with these characteristics may have a more aggressive form of the disease than those with MTL tumors associated with chronic epilepsy. (DOI: 10.3171/2009.5.FOCUS09106)Uribe JS, 2009, J NEUROSURG, V110, P137, DOI 10.3171/2008.4.17508PHI JH, 2009, CANCER IN PRESSPichlmeier U, 2008, NEURO-ONCOLOGY, V10, P1025, DOI 10.1215/15228517-2008-052McGirt MJ, 2008, NEUROSURGERY, V63, P700, DOI 10.1227/01.NEU.0000325729.41085.73Schramm J, 2008, ACTA NEUROCHIR, V150, P857, DOI 10.1007/s00701-008-0013-7Smith JS, 2008, J CLIN ONCOL, V26, P1338, DOI 10.1200/JCO.2007.13.9337van Breemen MSM, 2007, LANCET NEUROL, V6, P421Schramm J, 2007, NEUROSURGERY, V60, P285, DOI 10.1227/01.NEU.0000249281.69384.D7Cataltepe O, 2005, J NEUROSURG, V102, P280Clusmann H, 2004, J NEUROL NEUROSUR PS, V75, P1589, DOI 10.1136/jnnp.2003.024208Schramm J, 2004, NEUROSURGERY, V55, P340, DOI 10.1227/01.NEU.0000129546.38675.1BDoetsch F, 2003, NAT NEUROSCI, V6, P1127, DOI 10.1038/nn1144Luyken C, 2003, EPILEPSIA, V44, P822Bauman G, 1999, INT J RADIAT ONCOL, V45, P923Lote K, 1997, J CLIN ONCOL, V15, P3129Piepmeier J, 1996, NEUROSURGERY, V38, P872Duffner PK, 1996, J NEURO-ONCOL, V28, P245Campbell JW, 1996, NEUROSURGERY, V38, P258PRAYSON RA, 1993, EPILEPSIA, V34, P609YASARGIL MG, 1992, ACTA NEUROCHIR, V118, P40YASARGIL MG, 1992, ACTA NEUROCHIR, V116, P147