Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.

Decreased expression of survivin 2B in human pituitary adenomas. A preliminary study.

INTRODUCTION: We aimed to investigate survivin and its splice variants DEx3 and 2B expressions in pituitary adenomas and normal pituitary glands using immunohistochemistry. MATERIAL AND METHODS: The study group consisted of eight pituitary adenomas: five of non-functional tumors, two of GH-secreting tumors, and one PRL-secreting tumor. Eight healthy pituitary tissue samples obtained after autopsy served as controls. RESULTS: Survivin expression was found in 87.5% of the study group and 100% of the controls. A positive staining of survivin 2B was found in 62.5% of pituitary adenomas and 100% of controls. Survivin DEx3 was recognized in 25% of pituitary adenomas and 12.5% of normal pituitary glands. There was significantly lower immunoreactivity of survivin 2B in pituitary adenomas when compared with normal pituitary glands (p = 0.0498). CONCLUSIONS: Survivin and its splice variants might be involved to some extent in benign tumor growth of pituitary adenomas. However, survivin cannot be regarded as a candidate for targeted therapy or molecular biomarker of pituitary adenomas.

Expression of ghrelin and ghrelin functional receptor GHSR1a in human pituitary adenomas.

INTRODUCTION    Pituitary adenomas are heterogenous lesions commonly observed in the central nervous system. Signal transduction of ghrelin, an endogenous ligand specific for growth hormone secretagogue receptor (GHSR), has been reported to be involved in the development of endocrine tumors. However, there are limited data concerning the role of ghrelin and its functional receptor in pituitary adenomas. OBJECTIVES    The aim of the study was to establish the expression pattern of GHRL and its functional receptor GHSR1a in human pituitary adenomas. PATIENTS AND METHODS    Tissue specimens, including somatotropinomas (n = 20), prolactinomas (n = 5), and nonfunctioning adenomas (n = 52) were obtained from 77 patients. Thirteen normal pituitaries served as controls. The expression pattern of GHRL and GHSR1a mRNAs was established using reverse transcription followed by quantitative polymerase chain reaction. RESULTS    Ghrelin mRNA was detected in 92.2% of the samples including controls, while GHSR1a transcripts were detected in 54.4% of the cases. Significant differences were found among subgroups in the GHSR1a expression (P <0.0001) but not in that of GHRL (P = 0.7). The relative GHSR1a expression level was significantly lower for nonfunctioning tumors than for the control group or somatotropinomas. Controls revealed a strong positive correlation between the expression of both genes (r = 0.8; P <0.0001), unlike adenomas, which showed a weak negative correlation (r = -0.3; P >0.05). The maximum tumor diameter for nonfunctioning adenomas was higher than that for somatotropinomas (mean [SD], 31.4 [76] mm vs 24.8 [10.9] mm; P = 0.01). Neither the GHRL nor GHSR1a expression showed a significant correlation with tumor size in the subgroups. CONCLUSIONS    The presence of GHRL and GHSR1a in the neural system indicates their effect on pituitary function regulation and suggests their possible role in adenoma pathogenesis.

Ten years of experience in endovascular treatment of ruptured aneurysms of the posterior inferior cerebellar artery.

BACKGROUND: The aim of this study is to present our 10 years of experience in endovascular treatment of ruptured posterior inferior cerebellar artery (PICA) saccular aneurysms and to compare clinical presentation and outcome after endovascular treatment between patients with PICA aneurysms and patients with aneurysms in different locations. METHODS AND FINDINGS: Out of 932 patients with a ruptured intracranial aneurysm treated endovascularly in our institution, 38 aneurysms were located at the posterior inferior cerebellar artery. Clinical presentation, mean aneurysm diameter and outcome of the therapy in this group were compared with the same for ruptured aneurysms in other locations. Patients discharged with favourable outcomes were checked angiographically in the follow-up period. Thirty-four patients with ruptured PICA aneurysms were treated by selective endovascular coiling. Two patients with wide-necked aneurysms had endovascular stents implanted. In two cases, the parent vessel was occluded due to failure to catheterise the target aneurysm. The evaluated variables did not differ significantly between two groups, but significantly more ruptured aneurysms in the PICA group were under 6 mm in diameter. 29.4% of controlled aneurysms needed additional reembolisation in the follow-up period. CONCLUSIONS: Clinical presentation, extension of subarachnoid haemorrhage and outcome after endovascular treatment did not differ significantly between patients with ruptured aneurysms located on the PICA and patients with aneurysms located elsewhere intracranially. Endovascular treatment is an effective method of therapy in patients with ruptured PICA aneurysms. In our experience, even when sacrificing of the PICA is required, the results of treatment are favourable.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

Very late in-stent thrombosis 9 years after double stent treatment of fusiform basilar artery aneurysm.

Endovascular treatment seems to be the best approach to posterior circulation fusiform aneurysms. Double stent techniques are frequently used to occlude basilar artery dilations. Unfortunately, there is a limited number of studies that have followed up with patients over prolonged periods of time in order to evaluate delayed complications, such as stenosis, thrombosis or migration of stents. We present an unusual case of in-stent thrombosis 9 years after basilar artery aneurysm treatment to caution about complications associated with double stent implantation.

Extracranial Internal Carotid Artery Dissection Treated with Self-expandable Stents: A Single-Centre Experience.

PURPOSE: Treatment of choice for the internal carotid artery dissection (ICAD) is anticoagulation for three to 6 months. Endovascular procedures may be a promising alternative for patients (pts) with haemodynamic impairment, recurrent ischaemic symptoms or symptomatic pseudoaneurysms. Thus, the purpose of this study was to evaluate the efficacy and safety of carotid artery stenting in treatment of selected pts with extracranial ICAD. METHODS: This study involved 18 symptomatic pts with the mean age of 44.6 ± 10.4 years with ICAD treated with the use of self-expandable stents. Six months after primary procedures, pts were readmitted to hospital and physical examination followed by cerebral angiography was performed. In the late follow-up period, clinical evaluations completed by duplex Doppler ultrasonography were carried out every 6 months and at the end of the follow-up period. RESULTS: Nobody died and no life-threatening adverse events were observed during either the in-hospital stay or post-discharge follow-up period (median 21 months). Stent deployment immediately restored flow in the true lumen of ICA in all cases. However, residual blood flow through the false lumen was observed in one pt. Complete resolution of clinical symptoms was observed in 14 pts (78%), partial improvement in 2 (11%) and persistence of neurological deficit in 2 (11%). CONCLUSIONS: Implantation of self-expandable stents in treatment of selected extracranial ICAD cases is safe. This method may enable us to restore immediately and usually permanently proper arterial blood flow in the ICA and in consequence lead to significant clinical improvement in the late follow-up period.

Embolisation of internal carotid artery aneurysm using the double microcatheter technique - a case report.

BACKGROUND: A wide-necked aneurysm is defined as the one with a neck greater than 4 mm in diameter. Embolisation of wide-necked aneurysms is a great challenge for neuroradiologists. To overcome possible complications of endovascular treatment of this type of aneurysms, methods like intracranial stents, balloon remodelling, the double microcatheter and the microcatheter protective technique have been developed. CASE REPORT: We report a case of embolisation of a 63-year-old woman with a wide-necked aneurysm using the double microcatheter technique. Introduction of the second microcatheter into the aneurysm allowed for crossing two coils and prevented protrusion into the parent vessel, which resulted in successful treatment without postprocedural complications. Both postembolic and follow-up angiography showed complete exclusion of the aneurysm. CONCLUSIONS: The double microcatheter technique, owing to creation of a stable coil frame across the neck of the aneurysm, is suitable for treatment of aneurysms with an adverse dome-to-neck ratio. This technique is easy to perform for an experienced neuroradiologist.

Evaluation of survivin splice variants in pituitary tumors.

PURPOSE: Survivin is an apoptosis inhibitor, expressed in almost all types of human malignancies, but rarely in differentiated normal tissues. Recently, survivin gene splice variants with different anti-apoptotic activities have been reported. The current study was undertaken to examine the expression of survivin and its splice variants ∆Ex3 and 2ß in pituitary tumors, and to correlate the amount of particular transcripts with clinical staging in pituitary adenomas. Quantitative detection of survivin and its splice variants ∆Ex3 and 2ß transcripts in non-cancerous pituitary tissues (n = 12) and different types of pituitary tumor (n = 50). METHODS: Samples were collected from 50 pituitary tumors including 26 non-functional tumors, 21 GH-secreting tumors, 2 PRL-secreting tumors and 1 ACTH-secreting tumor. 12 normal pituitary glands received after autopsy served as a control of the study. 29 thyroid cancers tissues were used as a positive control. The RT-qPCR with TaqMan hydrolysis probes were used to determine the expression of analyzed splice variants of survivin. RESULTS: The obtained data showed that both survivin and its splice variants were expressed in different types of pituitary adenoma as well as in normal pituitary tissue. However, the level of its expression was similar in all studied cases. Patient age negatively correlated with tumor invasiveness. Moreover, our study showed a tendency for negative correlation between patient age and tumor diameter. CONCLUSIONS: No significant differences between survivin and its splice variants ∆Ex3 and 2ß expression in pituitary tumors and in normal pituitary glands as well as in invasive and in non-invasive tumors were found, suggesting that survivin does not play a significant role in pituitary tumorigenesis.

Evaluation of results of linac-based radiosurgery for brain metastases from primary lung cancer.

AIM: The purpose of our review was to evaluate results of radiosurgery for patients with brain metastases from lung cancer. BACKGROUND: Lung cancer is the leading cause of death from cancer and the most common source of brain metastases. Radiosurgery allows the precise focal delivery of a high single radiation dose to brain metastases and results in high rates of local control. MATERIALS AND METHODS: 83 patients were treated between 2006 and 2008. We evaluated local control and outcome after radiosurgery and identified prognostic factors. RESULTS: Median survival in the whole group was 7.8 months from radiosurgery and 11 months from diagnosis. Median survival in classes I, II and III was 13.2, 8.2 and 2.2 months. For 94% of patients symptoms improved or stabilised at the first follow-up visit and this status did not change during 7.1 months. According to the univariate analysis, factors associated with improved survival included: RPA class 1 compared with RPA 2 and 3, RPA class 2 compared with RPA 3, KPS > 70, control of the primary disease, radiosurgery performed more than once, level of haemoglobin >7 mmol/1, absence of extracranial metastases, volume of the biggest lesion <11 cm(3). The multivariate analysis confirmed a significant influence on survival for the following factors: RPA class 1 as compared with RPA 3, KPS > 70, absence of extracranial metastases, multiplicity of radiosurgery. CONCLUSIONS: Stereotactic radiosurgery is a safe and effective treatment. It proved to be effective and safe in older patients. Selection of patients who are likely to benefit most should be based on prognostic factors. KPS proved to be the most important prognostic factor. In the RPA III group (patients with KPS < 70) survival time was similar to that achieved after symptomatic medical management.

Survivin--prognostic tumor biomarker in human neoplasms--review.

Accurate diagnosis and proper monitoring of cancer patients remain important obstacles for successful cancer treatment. The search for cancer biomarkers is carried out in order to quickly identify tumor cells and predict treatment response, ultimately leading to a favorable therapeutic outcome. One such prognostic marker seems to be survivin. Many studies have shown that survivin is strongly expressed in a vast majority of cancers. Its overexpression was demonstrated in breast and lung cancer prostate, gastric, colon, bladder and esophageal carcinomas, osteosarcomas, and lymphomas. In many of those tumors, high activity of the surviving gene was associated with a poor prognosis and worse survival rates. Moreover survivin expression was correlated with resistance to chemotherapy and radiotherapy-induced apoptosis. Since survivin may be identified as an independent prognostic factor and inhibitor of apoptosis, it may prove to be a useful therapeutic target in cancer therapy

Pituitary abscess: a case report.

OBJECTIVES: Pituitary abscess is rare disease and the correct diagnosis is difficult because there are non-specific symptoms and it is often radiologically indistinguishable from other pituitary lesions. CASE PRESENTATION: We present one case of pituitary abscess that constitute 0.15% of all pituitary adenomas operated in our department in the 20 years. A 49-year-old woman presented with a history of 10 months bifrontal headache. The MRI showed cystic intra and suprasellar mass with ring enhancement after contrast injection. During transsphenoidal surgery, copious yellowish pus was found. Antibiotic therapy was performed. Histological study of the cyst wall confirmed the diagnosis of pituitary abscess. CONCLUSION: Pituitary abscess should be considered in the differential diagnosis of all other cyst mass in patients with diabetes insipidus.

Difficulties in diagnosis and treatment of acromegaly in a patient with a McCune-Albright syndrome. A case report and a review of literature.

We describe a female patient aged 43, who at the age of five was diagnosed with polyostotic fibrous dysplasia (FD). The patient was intermittently treated in our department since the age 33, for approximately 10 years, with intravenous bisphosphonates. At the age of 42 acromegaly was diagnosed incidentally, since clinical manifestations were poor, and, if present earlier, they had been related to FD. Only retrospectively, having biochemical confirmation of GH excess, we could relate them to acromegaly. Because of the involvement of the base of the skull there was no possibility of transphenoidal surgery. Long-acting somatostatin analogues were started, but no response was observed, with IGF-1 and GH being even higher during than before treatment. After the 37-year-history of FD, the occurrence of additional endocrine disorder enabled to make diagnosis of McCune-Albright syndrome (MAS) even in the absence of two out of three classical manifestations such as café-au-lait skin pigmentation and peripheral precocious puberty in the past medical history.

Coexpression of survivin and PCNA in pituitary tumors and normal pituitary.

OBJECTIVES: The survivin is the protein involved in regulation of basic and cycle-specific functions of cells both in normal and cancer tissue. Recent studies present survivin as a factor having the leading role in the regulation of apoptosis and mitosis as well as a target of anticancer therapy. The employing of survivin in this therapy is based on its high expression level in most human cancers, as well as its association with the disease's progression. The aim of our study was to evaluate the expression and localization of survivin's gene product on the protein level in different types of pituitary tumors and normal pituitary. The coexpression of survivin and proliferating cell nuclear antigen - PCNA in pituitary was also examined. DESIGN AND METHODS: The study was conducted on the postoperative pituitary tumors tissue taken during standard neurosurgical removal of tumor from 43 patients. The group of patients consists of 23 women and 20 men, aged from 27 to 71 years. As a control of the study three normal pituitary tissues obtained at the autopsy were used. Evaluation of survivin and PCNA expression was performed using immunohistochemical staining. RESULTS: The study demonstrated the presence of survivin in all analyzed by us pituitary tumors. Survivin was present also in normal pituitary tissue. The protein was localized mainly in cell's nuclei, however the less intense immunostaining was observed also in the cytoplasm of pituitary tumors cells. Furthermore survivin was found in normal pituitary, but the positive immunostaining was limited to a single cells. The analysis of pituitary tumor cells proliferation index based on PCNA reactivity showed that survivin is coexpressed with PCNA, especially in invasive tumors. CONCLUSIONS: The study documented the presence of survivin in different types of pituitary tumors as well as in normal pituitary. Additionally the coexpression of survivin and PCNA in tumor cells was shown. The expression of survivin in both normal and cancer pituitary cells suggests that it may play an important role in regulation of the gland's proliferation.

The expression of ghrelin in somatotroph and other types of pituitary adenomas.

OBJECTIVES: It has been suggested that ghrelin synthesized locally in pituitary regulates the function and growth of pituitary cells in autocrine/paracrine way and might be an important factor of pituitary tumorogenesis. The expression of ghrelin receptor in neoplastic cells of pituitary adenomas has also been demonstrated. In vitro studies confirmed that ghrelin stimulates the proliferation of somatotroph cells in GH3 cell line. The presence of both ghrelin mRNA and protein was detected in a number of benign and malignant neoplasms as well as in neoplastic cells of the tissues which do not express ghrelin in physiological conditions. This study showed the presence of ghrelin mRNA and its protein in different types of pituitary adenomas. DESIGN: The samples of 37 pituitary adenomas were obtained during standard neurosurgical tumor removal. The study tissues included 20 somatotroph tumors (15 patients treated and 5 patients untreated with octreotide LAR before the surgery), 12 nonfunctioning adenomas, 4 prolactinomas and 1 ACTH-secreting tumor. The control included samples of normal mucous membrane of the stomach and normal pituitaries. Expression of ghrelin mRNA was studied in 28 pituitary adenomas by RT-PCR. Immunohistochemical evaluation of ghrelin presence was performed in 34 tumors. RESULTS: The presence of ghrelin gene transcripts was demonstrated in 10 out of 15 examined somatotroph tumors (obtained from patients treated with octreotide LAR before the surgery) and also in 2 out of 4 samples of prolactinomas, 7 out of 8 of nonfunctioning tumors and in 2 samples of normal pituitary. Immunohistochemical analyses revealed the presence of the protein in all 5 examined somatotroph tumors obtained from patients not treated prior to the surgery and in 10 out of 15 tumors obtained from patients treated with octreotide LAR. The peptide was detected also in 10 out of 12 examined nonfunctioning tumors and in 2 examined PRL-secreting tumors. The immunostaining for ghrelin was not shown in normal pituitaries. CONCLUSIONS: The study demonstrated that ghrelin gene is expressed in somatotroph adenomas, both treated and untreated with octreotide LAR before the surgery, and also in other types of pituitary adenomas (prolactinomas and nonfunctioning adenomas).

Survivin products in pituitary tumors.

OBJECTIVES: Survivin is a member of the inhibitor of apoptosis protein family, which was recently showed to be expressed by different benign and malignant human tumors. Still very little is known about survivin expression in pituitary tumors. In spite of the fact that pituitary tumors in histological examination are usually benign, in the clinical process a certain number of pituitary adenomas is capable of aggressive growth, recurrence and invasion of the surrounding structures. The aim of the present study was to assess the presence of survivin transcripts and protein in different types of pituitary tumors and to evaluate survivin expression levels in invasive and non-invasive pituitary tumors. DESIGN AND METHODS: The analyzed material consisted of tumor tissue samples obtained during standard neurosurgical removal of the tumor from 23 patients in whom acromegaly (n=14), non-functioning pituitary tumor (n=6), prolactinoma (n=2) and corticotropinoma (n=1) were diagnosed. As a control of the study normal pituitary tissue obtained at autopsy was used. Amplification of survivin gene using sequence specific primers and qRT-PCR method and immunohistochemical staining with primary polyclonal antibodies against human survivin were performed. RESULTS: Our study demonstrated the presence of survivin mRNA in all 23 analyzed pituitary tumors. Survivin expression was also observed in normal pituitary, but the level of its expression was 6-fold lower than in tumors tissue when studied by real time RT-PCR. The difference between the levels of survivin expression in invasive and non-invasive tumors was not statistically significant. Immunohistochemical analyses revealed the presence of the protein in both normal and tumor tissue of pituitary. Immunostaining of tumor tissue was not uniform. Survivin was observed mainly in the nuclei of cells collected in clusters. The presence of the protein in normal pituitary was restricted to small population of cells. CONCLUSIONS: The present study showed that overexpression of survivin is characteristic for pituitary tumors. Further analysis of this protein expression profile should demonstrate whether survivin might be use as a prognostic marker in diagnosis and therapy of pituitary adenomas.

The evaluation of ghrelin mRNA expression in human somatotroph adenomas.

Ghrelin is one of the peptides involved into GH-release, binding to specific GHS receptors on hypothalamus and pituitary. The ghrelin peptide and ghrelin mRNA have been detected in several regions of hypothalamus, in normal pituitary, as well as in various types of pituitary adenoma, with different levels of expression in different tumour types. We decided to determine the expression of ghrelin in somatotroph adenomas. Human pituitary somatotroph adenoma tissues were obtained at the time of transsphenoidal surgery from 3 acromegalic patients and studied for ghrelin mRNA expression. Before surgery each patient received a somatostatin analogue treatment at doses 20 mg, 30 mg, 30 mg at 30 days intervals. 20 mg of each tissue sample was used for the isolation of total cellular RNA. The reverse transcription and real-time PCR were performed according to Korbonits et al. method. The reverse transcription of total RNA to cDNA was performed using Super Script TM Rnase H RT kit according to manufacturer protocol. We wished to determine the number of copies of ghrelin gene within the single cell. We used the beta-actin, and the GAPDH genes as a reference molecules for standard curve calculation. Ghrelin mRNA was not detected in any examined tissues. We postulate that the absence of the ghrelin gene transcript is mainly due to the treatment with somatostatin analogues administered preoperatively, which could have suppressed the ghrelin gene transcription.

[Sphenoid sinus surgery]. / Operacje zatoki klinowej.

Sphenoid sinus surgery due to specific localization is placed in otolaryngologists and neurosurgeons field of interest. Surgery of this area, from one side, causes number of problems, which usually arise due to close neighbourhood of important structures, but on the other, serves as alternative approach, eliminating necessity of extended operations with craniotomies. The article summarizes results of sphenoid sinus surgery at ENT Department, University of Medical Sciences in Poznan between 1990 and 2003, as well as points out characteristic features of the surgery in this specific localization.

Effects of treatment with somatostatin analogues on the occurrence of apoptosis in somatotropinomas.

OBJECTIVES: Apoptosis of endocrine cells represents one of factors significantly affected the control of hormones secretion. Present study aimed to examine whether treatment of somatotropinoma types tumours with somatostatine analogue (lanreotide) results in apoptosis. MATERIAL AND METHODS: The studies were performed on 35 patients with somatotropinoma type tumours on whom adenomectomy was performed by transsphenoidal approach. The operative material was examined by cellular morphology, based on light and electron microscopy and chromosomal ladder formation assay. RESULTS: The number of apoptotic cells showed features typical for the process as condensation and fragmentation of chromatin, vacuolisation, damage of the inner structure of mitochondria and oligonucleosomal fragmentation of DNA was found in the study material. The results of the studies demonstrated the occurrence of lanreotide induced apoptosis in somatotropinoma type tumours. The grade of apoptotic cells in macroadenomas type adenomas, treated with lanreotide, ranged from 4.0% to 17.1% (mean 8.7+/-2.6%). Patients in whom hypophysectomy was not preceded by lanreotide treatment demonstrated low level of apoptotic cells (no more than 3.5%). CONCLUSIONS: The studies showed that treatment with somatostatine analogue-lanreotide induced apoptosis of tumour cell suggesting that the induction of apoptotic cell death may be involved in the anticancer activity of somatostatine analogue.

Genomic instability in pituitary adenomas.

Pituitary adenomas most commonly are identified as small, incidental microadenomas. They however may progress to macroadenoma forming intra and later suprasellar tumors which in about 1/3 of cases invade surrounding structures at the time of diagnosis. Mechanism of pituitary tumorigenesis remains still elusive. Because the value of karyotyping is limited by the technical problems related to cytogenetic methods, we studied the spectrum of chromosomal imbalances associated with pituitary adenoma using comparative genomic hybridization (CGH). Copy number aberrations on all 22 autosomes were evaluated by CGH using advanced computer software. In total, fifteen patients were included in the study of 9 non-invasive, 4 invasive and two recurrent adenomas. The mean age of the patients were 48 years ranging from 36 to 68 years. Five tumors showed hormonal activity. The histogram of all 15 cases representing the DNA imbalances as an incidence curve along each chromosome showed losses particularly for chromosomes 1p, 2q, 4, 5, 6, 11q, 12q, 13q and 18q as well as overrepresentation on 9q, 16p, 17p, 19, 20q. Functioning adenomas carried more imbalances than non-functioning, specifically deletions on chromosome 4 and 18q as well as overrepresentations of chromosomes 17 and 19. Invasive adenomas carried more overrepresentations at 1p34 than non-invasive tumors. Recurrent adenomas harbored more alterations than primary tumors, particularly DNA gains. The primary data is accessible at our CGH online tumor database at http://amba.charite.de/cgh. Reviewing the existing literature on the genetics of pituitary adenoma and discussing our results in this context, we hope that our study will contribute to the knowledge of this neoplasm.