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1.
Invest Radiol ; 57(9): 567-574, 2022 09 01.
Article in English | MEDLINE | ID: mdl-35925660

ABSTRACT

OBJECTIVE: A prospective preoperative evaluation of 7 T ultra-high-field magnetic resonance imaging (MRI) in patients with suspected pituitary microadenomas for both adenoma detection and intrasellar localization compared with 3 T MRI was carried out. MATERIALS AND METHODS: Patients underwent prospective preoperative standardized 3 and 7 T MRI. A distinct qualitative (lesion detection, intrasellar lesion location) and quantitative (lesion diameters, T1/T2 signal intensity ratio of the lesion to normal pituitary gland tissue) analysis was performed, along with an evaluation of image quality (IQ) regarding overall IQ, anatomical parameters, and artifacts; the findings of the qualitative analysis were compared with intraoperative findings and endocrinological outcomes. RESULTS: Sixteen patients (mean age, 43 ± 16 years; 13 women) with pituitary microadenomas were included. Using 7 T MRI allowed the detection of 15 microadenomas-3 more than 3 T MRI. In addition, 7 T MRI allowed more precise lesion localization with 93.75% (15/16) agreement with intraoperative findings, compared with 75% (12/16) agreement using 3 T MRI. Lesion diameters showed no significant difference between 3 and 7 T MRI. T1 and T2 signal intensity ratio between microadenomas and normal pituitary gland tissue were higher in 7 T MRI than in 3 T MRI. The overall IQ and the IQ of each anatomical parameter of 7 T MRI were rated higher than those of 3 T MRI. No significant differences in susceptibility or head motion artifacts were observed between 3 and 7 T MRI; however, 7 T MRI was more susceptible to pulsation artifacts. CONCLUSION: Ultra-high-field MRI surpasses 3 T MRI in pituitary microadenoma detection and enables more precise delineation with higher correlation with intraoperative findings. Thus, 7 T sellar imaging is a promising option-especially in previously magnetic resonance-negative patients with endocrinologically confirmed hormone oversecretion-and helps reduce the need for invasive diagnostics.


Subject(s)
Adenoma , Pituitary Neoplasms , Adenoma/diagnostic imaging , Adenoma/surgery , Adult , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Pituitary Gland/pathology , Pituitary Gland/surgery , Pituitary Neoplasms/diagnostic imaging , Pituitary Neoplasms/pathology , Prospective Studies
2.
Diagnostics (Basel) ; 12(5)2022 May 04.
Article in English | MEDLINE | ID: mdl-35626296

ABSTRACT

Treated cerebral aneurysms (IA) require follow-up imaging to ensure occlusion. Metal artifacts complicate radiologic assessment. Our aim was to evaluate an innovative metal-artifact-reduction (iMAR) algorithm for flat-detector computed tomography angiography (FD-CTA) regarding image quality (IQ) and detection of aneurysm residua/reperfusion in comparison to 2D digital subtraction angiography (DSA). Patients with IAs treated by endovascular coiling or clipping underwent both FD-CTA and DSA. FD-CTA datasets were postprocessed with/without iMAR algorithm (MAR+/MAR−). Evaluation of all FD-CTA and DSA datasets regarding qualitative (IQ, MAR) and quantitative (coil package diameter/CPD) parameters was performed. Aneurysm occlusion was assessed for each dataset and compared to DSA findings. In total, 40 IAs were analyzed (ncoiling = 24; nclipping = 16). All iMAR+ datasets demonstrated significantly better IQ (pIQ coiling < 0.0001; pIQ clipping < 0.0001). iMAR significantly reduced the metal-artifact burden but did not affect the CPD. iMAR significantly improved the detection of aneurysm residua/reperfusion with excellent agreement with DSA (naneurysm detection MAR+/MAR−/DSA = 22/1/26). The iMAR algorithm significantly improves IQ by effective reduction of metal artifacts in FD-CTA datasets. The proposed algorithm enables reliable detection of aneurysm residua/reperfusion with good agreement to DSA. Thus, iMAR can help to reduce the need for invasive follow-up in treated IAs.

3.
Life (Basel) ; 13(1)2022 Dec 24.
Article in English | MEDLINE | ID: mdl-36675998

ABSTRACT

To compare 7 T magnetic resonance imaging (MRI) of pituitary macroadenomas (PMA) with standard MRI and intraoperative findings regarding tumor detection, localization, size, and extension. Patients with suspected pituitary adenoma underwent pre-operative 1.5 T or 3 T and 7 T MRI; 14 patients with a PMA were included. A qualitative (lesion detection, location, cavernous sinus infiltration) and quantitative (lesion size, depth of cavernous sinus infiltration) analysis of 1.5 T, 3 T and 7 T MRI was performed and compared with intraoperative findings. Both 1.5/3 T and 7 T MRI enabled the detection of all PMAs; lesion size determination was equal. 7 T MRI enables more precise assessments of cavernous sinus infiltration of PMA (ncorrect 7T = 78.6%, ncorrect 1.5/3T = 64.3%). Ultra-high-field MRI is a reliable imaging modality for evaluation of PMAs providing exact information on lesion location and size. 7 T MRI yielded more accurate information on cavernous sinus infiltration with better agreement with intraoperative findings than standard MRI.

4.
J Endocr Soc ; 4(7): bvaa068, 2020 Jul 01.
Article in English | MEDLINE | ID: mdl-32666012

ABSTRACT

CONTEXT: The relevance of hyponatremia has been acknowledged by guidelines from the United States (2013) and Europe (2014). However, treatment recommendations differ due to limited evidence. OBJECTIVE: In hyponatremia following pituitary surgery-caused by the syndrome of inappropriate antidiuretic hormone (SIADH) secretion-we compared fluid restriction with the pharmacological increase of water excretion by blocking the vasopressin 2 receptors with tolvaptan at a low and a moderate dose. DESIGN: Prospective observational study. SETTING: Neurosurgical Department of a University hospital with more than 200 surgical pituitary procedures per year. PATIENTS: Patients undergoing pituitary surgery and developing serum sodium below 136 mmol/L. The diagnosis of SIADH was established by euvolemia (daily measurement of body weight and fluid balance), inappropriately concentrated urine (specific gravity), and exclusion of adrenocorticotropic and thyroid-stimulating hormone deficiency. INTERVENTION: Patients were treated with fluid restriction (n = 40) or tolvaptan at 3.75 (n = 38) or 7.5 mg (n = 48). MAIN OUTCOME MEASURES: Treatment efficacy was assessed by the duration of hyponatremia, sodium nadir, and length of hospitalization. Safety was established by a sodium increment below 10 mmol/L per day and exclusion of side effects. RESULTS: Treatment with 7.5 mg of tolvaptan resulted in a significant attenuation of hyponatremia and in a significant overcorrection of serum sodium in 30% of patients. The duration of hospitalization did not differ between treatment groups. CONCLUSIONS: Tolvaptan at a moderate dose is more effective than fluid restriction in the treatment of SIADH. Overcorrection of serum sodium may be a side effect of tolvaptan even at low doses.

5.
Rev Endocr Metab Disord ; 21(2): 253-261, 2020 06.
Article in English | MEDLINE | ID: mdl-32500483

ABSTRACT

Surgery of aggressive pituitary adenomas and pituitary carcinomas is part of the interdisciplinary management of these difficult to treat tumors. Invasion, giant size and unusual, asymmetric extent of these tumors frequently require modifications or extensions of the standard approaches for transsphenoidal and transcranial surgery. Frequently, only debulking procedures can be performed. In aggressive and hormone secreting adenomas, the remission rates achieved by surgery alone are relatively poor and adjuvant medical treatments or irradiation are needed. Safe resection of as much tumor as possible and symptomatic control is aimed at, rather than remission. Many procedures are required for rapid progression of lesions or recurrences, in order to extend the survival of the patients. Metastases of pituitary carcinomas within the cranial cavity or spine can be attacked. Since they can occur anywhere in the brain or spinal canal they require the entire battery of neurosurgical approaches. Unfortunately, in this group of pituitary tumors, the complication rates are higher than in primary operations of enclosed adenomas. The respective techniques with their facilities and limitations are reviewed in this article.


Subject(s)
Adenoma/surgery , Carcinoma/surgery , Neoplasm Invasiveness , Pituitary Neoplasms/surgery , Adenoma/pathology , Carcinoma/pathology , Humans , Neoplasm Invasiveness/pathology , Pituitary Neoplasms/pathology
6.
Neuroendocrinology ; 110(9-10): 836-847, 2020.
Article in English | MEDLINE | ID: mdl-32541136

ABSTRACT

Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspecific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.


Subject(s)
Chondrosarcoma , Chordoma , Skull Base Neoplasms , Chondrosarcoma/classification , Chondrosarcoma/pathology , Chondrosarcoma/radiotherapy , Chondrosarcoma/surgery , Chordoma/classification , Chordoma/pathology , Chordoma/radiotherapy , Chordoma/surgery , Humans , Skull Base Neoplasms/classification , Skull Base Neoplasms/pathology , Skull Base Neoplasms/radiotherapy , Skull Base Neoplasms/surgery
7.
Neuroendocrinology ; 109(1): 77-81, 2019.
Article in English | MEDLINE | ID: mdl-30699424

ABSTRACT

While in the past surgery for prolactinomas was a competitive option to medical treatment with dopamine agonists, to date the indications for operations are restricted to only a few specific situations. However, if a patient is intolerant to medical treatment or if the drugs are not sufficiently effective in terms of lowering prolactin levels or tumor shrinkage, surgery should always be considered. In microprolactinomas, operations can achieve excellent prolactin normalization rates. In tumors difficult to treat, the combination of surgical tumor resection and long-term medical treatment supports better control of the disease. The individual indications, results, techniques, and complications of operations for prolactinomas are briefly reviewed in this paper.


Subject(s)
Neurosurgical Procedures/methods , Pituitary Neoplasms/surgery , Prolactinoma/surgery , Female , Humans , Male
8.
Front Genet ; 9: 49, 2018.
Article in English | MEDLINE | ID: mdl-29520296

ABSTRACT

A 6-year old patient presented with an intra and suprasellar cystic lesion accompanied with impairment of the hypothalamic-pituitary axis and partial hypopituitarism. The most likely cause of sellar lesions in this age group are adamantinomatous craniopharyngioma (adaCP) or Rathke´s cleft cysts (RCCs). AdaCP are characterized by CTNNB1 mutations accompanied with aberrant nuclear beta-catenin expression. RCC show neither nuclear beta-catenin expression nor BRAF mutation. The latter is a hallmark of papillary craniopharyngiomas (papCP) that exhibit remarkable histological similarity with metaplasia of RCC. Diagnosis of the patient was elucidated by CTNNB1 and BRAF mutation screening, utilizing different approaches, as well as histological examination of markers, e.g., beta-catenin, claudin-1, EpCAM and the mutated BRAFV600E protein, which are known to be differentially expressed in sellar lesions. The case presented reveals extraordinary aspects for two reasons. Firstly, the lesion appeared clinically, on MRI, intraoperatively and histologically as RCC with prominent squamous metaplasia, but showing an expression pattern of markers also found in papCP, whilst exhibiting a hitherto undescribed BRAFV600E mutation. This important result documents a supposable transition of RCC metaplasia into a papillary craniopharyngioma (papCP). Secondly, this intriguing case shows unexpectedly that although papCP usually occurs almost exclusively in adults, it can also arise in childhood.

9.
Pituitary ; 20(1): 76-83, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27770308

ABSTRACT

PURPOSE: Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed. METHODS: Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly. RESULTS: The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging. CONCLUSIONS: For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.


Subject(s)
Acromegaly/surgery , Acromegaly/metabolism , Algorithms , Female , Growth Hormone/metabolism , Humans , Insulin-Like Growth Factor I/metabolism , Male , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/surgery
10.
Front Horm Res ; 45: 121-32, 2016.
Article in English | MEDLINE | ID: mdl-27003942

ABSTRACT

Surgery for pituitary adenomas attempts the optimally possible amount of tumor resection, which ideally is total excision. However, there are limitations in the resectability and in the intraoperative assessment of the radicality of an adenomectomy. Postoperative imaging is usually performed with a few months delay after tumor resection. Intraoperative magnetic resonance imaging (MRI) is used to depict the extent of tumor removal already achieved in the operating theater during surgery. To date, there are different low- and high-field intraoperative MRI systems available. Decompression of optic pathways, preservation of the pituitary and residual tumor can be largely predicted from the intraoperative images. Several studies convincingly show that intraoperative depiction of residual tumor allows targeted attack of the remnant. Not only is the amount of tumor resected increased, but also the percentage of total tumor excisions. Intraoperative MRI provides an immediate feedback to the surgeon and is thus a valuable quality control for pituitary surgery. It also allows the acquisition of data sets for precise intraoperative navigation. However, the MRI scanners are heavy and expensive and some systems even require extensive modification of the operating theater. Imaging slightly prolongs the operation but is not associated with an increased complication rate. There are also potential artifacts which must be considered.


Subject(s)
Adenoma/surgery , Magnetic Resonance Imaging/methods , Monitoring, Intraoperative/methods , Pituitary Neoplasms/surgery , Adenoma/diagnostic imaging , Humans , Pituitary Neoplasms/diagnostic imaging
11.
Neuroendocrinology ; 103(1): 32-41, 2016.
Article in English | MEDLINE | ID: mdl-26536097

ABSTRACT

Since the establishment of transsphenoidal microsurgery as the operative treatment of choice in most patients with acromegaly 40 years ago, a few novel technical developments have evolved. Their application, utility and efficacy will be briefly discussed in this review article, based on an analysis of published results and the authors' personal experience. The endoscope was additionally used to search for residual tumours in locations which could not be visualised with the operating microscope. In many centres it has by now fully replaced the operating microscope. Extended endoscopic operations hardly have limits in respect to accessible pathology. Overall, the results and complications reported from microsurgical and endoscopic series are comparable. Intraoperative magnetic resonance imaging allows depicting the completeness of a tumour resection. While in many patients additional tumour resections are performed on the basis of intraoperative imaging, the improvements in hormonal remission rates reported are less impressive. Neuronavigation uses imaging data to improve the surgeon's orientation, and it is certainly a major asset to the inexperienced. In high-caseload centres it is mainly appreciated in anatomical variants and reoperations. While the Doppler probe is a valuable and easily affordable gadget to avoid vascular arterial injury, intraoperative ultrasound imaging of tumour extension has a much poorer resolution than magnetic resonance imaging and is thus not widely implemented. The clinical value of intraoperative growth hormone measurements is controversially discussed. In summary, the application of modern technology has only led to a minor improvement of results, but it has widened the spectrum of accessible pathologies and increased the safety of the procedures for the patient. It is expected that outcomes will continue to improve as novel techniques and concepts are being developed.


Subject(s)
Acromegaly , Magnetic Resonance Imaging , Neoplasm, Residual/surgery , Neuronavigation , Pituitary Neoplasms/surgery , Endoscopy/methods , Humans , Magnetic Resonance Imaging/methods , Neuronavigation/methods
12.
Brain Pathol ; 25(1): 1-10, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24716541

ABSTRACT

Adamantinomatous craniopharyngiomas (adaCP) cause hypothalamic pituitary dysfunction. Elucidation of pathomechanisms underlying tumor progression is essential for the development of targeted chemotherapeutic treatment options. In order to study the mechanisms of tumor outgrowth, we implanted human primary adaCP tissue from three different surgical specimens stereotactically into the brain of immunodeficient mice (n = 20). Three months after tumor inoculation, magnetic resonance imaging and histology confirmed tumor engraftment in all 20 mice (100%) that obtained tissue transplants. The lesions invaded adjoining brain tissue with micro finger-shaped protrusions. Immunohistochemical comparison of the primary tumor and xenotransplants revealed a similar amount of proliferation (Mib-1) and cytokeratin expression pattern (KL-1). Whole tumor reconstruction using serial sections confirmed whirl-like cell clusters with nuclear ß-catenin accumulations at the tumor brain border. These whirls were surrounded by a belt of Claudin-1 expressing cells, showed an activated epidermal growth factor receptor (EGFR) and distinct CD133 as well as p21(WAF1/Cip1) positivity, indicating a tumor stem cell phenotype. Consistent with our previous in vitro studies, intracranial xenotransplants of adaCP confirmed cells with nuclear ß-catenin and activated EGFR being the driving force of tumor outgrowth. This model provides the possibility to study in vivo tumor cell migration and to test novel treatment regimens targeting this tumor stem cell niche.


Subject(s)
Brain Neoplasms/physiopathology , Brain/physiopathology , Craniopharyngioma/physiopathology , Adolescent , Adult , Animals , Brain/pathology , Brain Neoplasms/pathology , Claudin-1/metabolism , Craniopharyngioma/pathology , Disease Progression , ErbB Receptors/metabolism , Female , Humans , Immunohistochemistry , Keratin-1 , Keratins, Hair-Specific/metabolism , Magnetic Resonance Imaging , Male , Mice, Mutant Strains , Middle Aged , Neoplasm Transplantation , Ubiquitin-Protein Ligases/metabolism , beta Catenin/metabolism
13.
Acta Neurochir (Wien) ; 156(10): 1865-78, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25085541

ABSTRACT

BACKGROUND: Hypothalamic harmartomas (HHs) are either occasionally associated with medically intractable epileptic syndromes or precocious puberty. Due to the extraordinary location and the expansive intra-axial growth, surgical resection is difficult and challenging without causing severe neurological, hypothalamic or endocrinological deficits, which account for higher mortality and morbidity. METHODS: We present a series of five adult patients with drug-resistant epilepsy who had been operated on for HH using neuronavigation and intraoperative 1.5-T magnetic resonance imaging (MRI). In this retrospective investigation, we compared our surgical strategy and postoperative results to existing series. RESULTS: During surgery, we identified remnant HH in the first intraoperative MRI control scan in three out of five patients. After re-segmentation of the residual lesion using neuronavigation, complete resection was achieved in two of the three patients as confirmed by final intraoperative and late follow-up MRI, raising the rate of total resections to four out of five patients. Two patients died during the observation period. One patient suffered from a permanent third nerve palsy and one from a transient monoparesis of the left arm. New endocrinological disturbances included diabetes insipidus centralis in two and secondary hypothyroidism and hypogonadism in one patient. Four out of five patients had favourable seizure control (Engel I or II) after 64.8 (34-83) months of mean follow-up. CONCLUSIONS: Neuronavigation and intraoperative MRI are valuable tools to encounter difficulties while performing surgery in patients with HHs. Intraoperative resection control increases the amount of maximum resection.


Subject(s)
Epilepsy/surgery , Hamartoma/surgery , Hypothalamic Diseases/surgery , Magnetic Resonance Imaging/methods , Monitoring, Intraoperative/methods , Neurosurgical Procedures/methods , Postoperative Complications , Adult , Epilepsy/etiology , Female , Hamartoma/complications , Humans , Hypothalamic Diseases/complications , Male , Neuronavigation/methods , Neurosurgical Procedures/adverse effects , Retrospective Studies , Treatment Outcome , Young Adult
14.
J Clin Endocrinol Metab ; 99(10): 3718-27, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25013998

ABSTRACT

CONTEXT: Pituitary effects of long-term therapy with mifepristone, a glucocorticoid receptor antagonist, in Cushing's disease (CD) patients are not well understood. OBJECTIVE: Our objective was to report changes in ACTH and pituitary magnetic resonance imaging (MRI) findings during long-term use of mifepristone in CD patients. DESIGN AND SETTING: The Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC) was a 24-week, open-label study of mifepristone, and its long-term extension (LTE) is a multicenter U.S. study. PATIENTS: Forty-three CD patients (mean age 45.3 years) were enrolled in SEISMIC with 27 continuing into the LTE study. INTERVENTIONS: Mifepristone (300-1200 mg) was administered once daily. MAIN OUTCOME MEASURES: ACTH and pituitary MRI were assessed at baseline and at regular intervals during treatment. RESULTS: A ≥2-fold increase in ACTH was observed in 72% of patients treated for a median duration of 11.3 months. The mean peak increase in ACTH was 2.76 ± 1.65-fold during SEISMIC, and mean ACTH concentrations remained stable during the LTE. ACTH was directly correlated with mifepristone dose and declined to near baseline levels after mifepristone discontinuation. Tumor regressed in 2 patients and progressed in 3 patients with macroadenomas. An additional microadenoma was identified after 25 months of treatment after a baseline tumor-negative MRI. CONCLUSIONS: In the largest prospective study to date, long-term mifepristone treatment increased ACTH in approximately two-thirds of patients with CD. ACTH elevations were observed within the first few weeks of treatment, were dose-dependent, and generally remained stable over time. Corticotroph tumor progression and regression may occur over time, but patients may have significant increases in ACTH levels without evidence of tumor growth.


Subject(s)
Adrenocorticotropic Hormone/blood , Mifepristone/administration & dosage , Pituitary ACTH Hypersecretion/drug therapy , Receptors, Glucocorticoid/antagonists & inhibitors , Adenoma/drug therapy , Adenoma/metabolism , Adenoma/pathology , Adult , Corticotrophs/metabolism , Corticotrophs/pathology , Female , Hormone Antagonists/administration & dosage , Hormone Antagonists/adverse effects , Humans , Hydrocortisone/blood , Magnetic Resonance Imaging , Male , Middle Aged , Mifepristone/adverse effects , Pituitary ACTH Hypersecretion/metabolism , Pituitary ACTH Hypersecretion/pathology , Pituitary Neoplasms/drug therapy , Pituitary Neoplasms/metabolism , Pituitary Neoplasms/pathology , Prospective Studies
15.
Neuro Oncol ; 16(2): 256-64, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24305709

ABSTRACT

BACKGROUND: Claudins are tight junction proteins expressed in epithelial tissues that play important roles in cell polarity and adhesion. Altered distribution of claudin-1(CLDN1) affects cell mobility and tumor invasiveness. Craniopharyngiomas (CPs) represent epithelial tumors of the sellar region, consisting of adamantinomatous (adaCP) and papillary (papCP) variants. Their tendency to infiltrate surrounding brain structures complicates successful surgery. Reliable markers are required to predict tumor behavior and to establish individualized treatment protocols. METHODS: We describe the distribution pattern of CLDN1 in a large cohort of 66 adaCPs, 21 papCPs, and 24 Rathke`s cleft cyst (RCC) cases using immunohistochemistry. CLDN1 mRNA levels were analyzed with qRT-PCR in 33 CP samples. The impact on the migration potential was studied in primary adaCP cell cultures (n = 11) treated with small interfering RNA (siRNA) for CLDN1. Furthermore, CLDN1 distribution patterns and expression levels were compared between invasive (n = 16) and noninvasive (n = 17) tumor groups. RESULTS: PapCPs and RCCs exhibited a distinct homogenous and membranous expression pattern, whereas CLDN1 immunoreactivity appeared weaker and more heterogeneous in adaCPs. In the latter cases, whirl-like cell clusters showed complete absence of CLDN1. mRNA analysis confirmed reduced CLDN1 levels in adaCPs versus papCPs. Interestingly, invasive tumors exhibited significantly lower CLDN1 expression compared with noninvasive counterparts regardless of CP subtype. Accordingly, siRNA treatment for CLDN1 altered tumor cell migration in vitro. CONCLUSION: CLDN1 represents a novel marker in the differential diagnosis of CP variants and RCCs. Low CLDN1 expression levels correlate with an invasive CP growth pattern and may serve as a prognostic marker.


Subject(s)
Carcinoma, Papillary/pathology , Claudin-1/metabolism , Craniopharyngioma/pathology , Pituitary Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Apoptosis , Blotting, Western , Carcinoma, Papillary/genetics , Carcinoma, Papillary/metabolism , Cell Movement , Cell Proliferation , Child , Child, Preschool , Claudin-1/antagonists & inhibitors , Claudin-1/genetics , Cohort Studies , Craniopharyngioma/genetics , Craniopharyngioma/metabolism , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Pituitary Neoplasms/genetics , Pituitary Neoplasms/metabolism , Prognosis , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured , Young Adult
16.
Pituitary ; 17(6): 546-56, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24356780

ABSTRACT

INTRODUCTION: Early disease onset, clinical manifestation, histomorphology, and increased tendency to relapse distinguish the adamantinomatous craniopharyngioma (adaCP) from the more favorable papillary variant (papCP). A molecular hallmark of adaCP is the activated Wnt signaling pathway indicated by nuclear ß-catenin accumulation in a subset of tumor cells. A mouse model recently illustrated that these cells are the driving force in tumorigenesis of adaCP. This observation and the peculiar growth pattern points to the existence of a specific tumor stem cell (TSC) population in human CP. MATERIALS AND METHODS: To prove this hypothesis, the TSC markers CD133 (Prominin1) and CD44 were examined in papCP (n = 8) and adaCP (n = 25) on mRNA level using quantitative real time PCR of total tumor RNA. Furthermore, we investigated protein expression performing immunohistochemical analyses of formalin-fixed paraffin embedded tumor samples. RESULTS: PapCP revealed a homogenous CD44 expression pattern predominantly at the cell membrane, whereas CD133 labeling was hardly detectable. In adaCP, on the other hand all markers were consistently and predominantly co-expressed in nuclear ß-catenin accumulating cell clusters, which was confirmed by double immunofluorescence staining. Overall expression of CD44 was significantly decreased in adaCP versus papCP, whereas CD133 showed significantly higher protein and mRNA levels in adaCP. CONCLUSIONS: Our results indicate tumor stem cell-like characteristics of ß-catenin accumulating cell clusters in adaCP, which may represent a tumor stem cell niche and might contribute to tumor recurrence. The potential impact of these special cell groups in regard to future CP management, including postoperative follow-up and additional treatment remains to be explored.


Subject(s)
Biomarkers, Tumor , Craniopharyngioma/pathology , Neoplastic Stem Cells/pathology , Pituitary Neoplasms/pathology , Wnt Signaling Pathway , AC133 Antigen , Adolescent , Adult , Antigens, CD/metabolism , Child , Child, Preschool , ErbB Receptors/metabolism , Exons , Extracellular Matrix Proteins/metabolism , Female , Glycoproteins/metabolism , Humans , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Hyaluronic Acid/metabolism , Male , Middle Aged , Osteopontin/metabolism , Peptides/metabolism , Signal Transduction , Young Adult , beta Catenin/metabolism
17.
Acta Neurochir (Wien) ; 155(11): 2177-82; discussion 2182, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24026232

ABSTRACT

BACKGROUND: One of the major concerns in transsphenoidal surgery are infections because the approach to the pituitary includes a route of microbial colonization. To minimize the associated morbidity and mortality, a surveillance program is crucial to monitor for perioperative infections. METHODS: For 1 year, we analysed body temperature (BT), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), C-reactive protein (CRP), interleukin 6 (IL-6) and lipopolysaccharide-binding-protein (LBP) following elective transsphenoidal pituitary surgery. Samples were collected on admission, day 1, 3 and 7 as well as 3 months postoperatively. RESULTS: In 116 patients, all data were available. No postoperative infections occurred within the first postoperative week. BT (37.6 ± 0.6, baseline 37.0 ± 0.5 °C), WBC (11,366 ± 2,541, baseline 6,861 ± 2,123/µl), CRP (25.3 ± 22.6, baseline 3.1 ± 6 mg/l), IL-6 (12 ± 13, baseline 2.7 ± 2.6 pg/ml), and LBP (11.3 ± 4.9, baseline 5.7 ± 2.7 µg/ml) peaked on day 1 postoperatively (each p = 0.001), while ESR peaked on day 3 (25 ± 16, baseline 13 ± 11 mm/h, p = 0.001). BT and IL-6 normalized by day 3 and CRP by day 7, while ESR (23 ± 16 mm/h, p = 0.001), WBC (7,807 ± 2,750/µl, p = 0.001) and LBP (7.3 ± 2.6 µg/ml, p = 0.028) were still increased by day 7. CONCLUSION: The present study establishes normative values for an infection surveillance following transsphenoidal pituitary surgery. CRP, a convenient and reasonable priced parameter, is affected by the procedure for the first postoperative week. IL-6 is more robust and allows a close monitoring on the expense of additional pricing. ESR, WBC and LBP are sustained affected by surgery, and do not offer any advantage. Since no infections were observed, we were unable to calculate the respective sensitivity and specificity.


Subject(s)
Body Temperature/physiology , C-Reactive Protein/analysis , Carrier Proteins/blood , Interleukin-6/blood , Membrane Glycoproteins/blood , Pituitary Gland/surgery , Surgical Wound Infection/diagnosis , Acute-Phase Proteins , Adult , Aged , Aged, 80 and over , Blood Sedimentation , C-Reactive Protein/ultrastructure , Female , Humans , Leukocyte Count/methods , Male , Middle Aged , Postoperative Complications/blood , Surgical Wound Infection/blood
18.
Pituitary ; 16(1): 18-25, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22836237

ABSTRACT

Craniopharyngiomas are rare benign sellar region tumors, which are diagnosed either in childhood or adolescence due to local mass effects on visual pathways, pituitary and hypothalamus, or because of an increased intracranial pressure resulting from obstructive hydrocephalus. The neurosurgeons challenge is to achieve tumor control without aggravating the symptoms. There are essentially two different surgical philosophies. Although only gross tumor resection has been proven to provide cure, the accompanying surgical hazard is substantial. Thus, less aggressive operations with partial or subtotal tumor resection or drainage of cystic portions followed by irradiation may relieve the patient's symptoms and benefit the patient more than a heroic tumor resection-since to date several variants of radiation therapy are available which also serve to control tumor progression. In the present brief review, the surgical techniques and outcomes of operations in craniopharyngiomas with special focus on the resulting morbidity and mortality are summarized.


Subject(s)
Craniopharyngioma/surgery , Pituitary Neoplasms/surgery , Craniotomy , Humans , Treatment Outcome
19.
Endocrine ; 42(3): 483-95, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22833429

ABSTRACT

Surgery for pituitary adenomas still remains a mainstay in their treatment, despite all advances in sophisticated medical treatments and radiotherapy. Total tumor excision is often attempted, but there are limitations in the intraoperative assessment of the radicalism of tumor resection by the neurosurgeon. Standard postoperative imaging is usually performed with a few months delay from the surgical intervention. The purpose of this report is to review briefly the facilities and kinds of intraoperative magnetic resonance imaging for all physician and surgeons involved in the management of pituitary adenomas on the basis of current literature. To date, there are several low- and high-field magnetic resonance imaging systems available for intraoperative use and depiction of the extent of tumor removal during surgery. Recovery of vision and the morphological result of surgery can be largely predicted from the intraoperative images. A variety of studies document that depiction of residual tumor allows targeted attack of the remnant and extent the resection. Intraoperative magnetic resonance imaging offers an immediate feedback to the surgeon and is a perfect quality control for pituitary surgery. It is also used as a basis of datasets for intraoperative navigation which is particularly useful in any kind of anatomical variations and repeat operations in which primary surgery has distorted the normal anatomy. However, setting up the technology is expensive and some systems even require extensive remodeling of the operation theatre. Intraoperative imaging prolongs the operation, but may also depict evolving problems, such as hematomas in the tumor cavity. There are several artifacts in intraoperative MR images possible that must be considered. The procedures are not associated with an increased complication rate.


Subject(s)
Adenoma/surgery , Magnetic Resonance Imaging/methods , Monitoring, Intraoperative/methods , Pituitary Neoplasms/surgery , Acromegaly/etiology , Acromegaly/surgery , Adenoma/complications , Adenoma/pathology , Electromagnetic Fields , Endoscopy , Humans , Magnetic Resonance Imaging/instrumentation , Pituitary Neoplasms/complications , Pituitary Neoplasms/pathology
20.
Neurosurgery ; 69(4): 852-62; discussion 862-3, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21623242

ABSTRACT

BACKGROUND: The beneficial role of the extent of resection (EOR) in glioma surgery in correlation to increased survival remains controversial. However, common literature favors maximum EOR with preservation of neurological function, which is shown to be associated with a significantly improved outcome. OBJECTIVE: In order to obtain a maximum EOR, it was examined whether high-field intraoperative magnetic resonance imaging (iMRI) combined with multimodal navigation contributes to a significantly improved EOR in glioma surgery. METHODS: Two hundred ninety-three glioma patients underwent craniotomy and tumor resection with the aid of intraoperative 1.5 T MRI and integrated multimodal navigation. In cases of remnant tumor, an update of navigation was performed with intraoperative images. Tumor volume was quantified pre- and intraoperatively by segmentation of T2 abnormality in low-grade and contrast enhancement in high-grade gliomas. RESULTS: In 25.9% of all cases examined, additional tumor mass was removed as a result of iMRI. This led to complete tumor resection in 20 cases, increasing the rate of gross-total removal from 31.7% to 38.6%. In 56 patients, additional but incomplete resection was performed because of the close location to eloquent brain areas. Volumetric analysis showed a significantly (P < .01) reduced mean percentage of tumor volume following additional further resection after iMRI from 33.5% ± 25.1% to 14.7% ± 23.3% (World Health Organization [WHO] grade I, 32.8% ± 21.9% to 6.1% ± 18.8%; WHO grade II, 24.4% ± 25.1% to 10.8% ± 11.0%; WHO grade III, 35.1% ± 27.3% to 24.8% ± 26.3%; WHO grade IV, 34.2% ± 23.7% to 1.2% ± 16.2%). CONCLUSION: MRI in conjunction with multimodal navigation and an intraoperative updating procedure enlarges tumor-volume reduction in glioma surgery significantly without higher postoperative morbidity.


Subject(s)
Brain Neoplasms/pathology , Brain Neoplasms/surgery , Diffusion Magnetic Resonance Imaging/methods , Glioma/pathology , Glioma/surgery , Neuronavigation/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult
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