Recurrence in acromegaly: two tertiary centers experience and review of the literature.

BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.

Impact of age on postsurgical outcomes of nonfunctioning pituitary adenomas.

PURPOSE: The management of pituitary adenomas in the elderly has become a relevant clinical issue, in relationship with improved life expectancy and spreading use of imaging techniques. In this single-center and retrospective study, we investigated the impact of age on peri- and postsurgical outcomes in patients undergoing transnasal sphenoidal (TNS) surgery for pituitary adenomas. METHODS: One-hundred-sixty-nine patients (62% males) undergoing endoscopic transphenoidal (TNS) surgery for nonfunctioning pituitary adenomas (NFPAs) were enrolled. Patients were subdivided into three groups according to age tertiles: ≤56 (group 1), 57-69 (group 2), and ≥70 (group 3) years. Postsurgical and endocrinological outcomes were evaluated and compared among the three age groups. RESULTS: 37/169 patients (21.9%) developed at least one perisurgical complication, without significant association with the patients' age (P = 0.838), Charlson co-morbidity score (P = 0.326), and American Society of Anesthesiologist score (P = 0.616). In the multivariate regression analysis, the adenoma size resulted the only determinant of perisurgical complication (odds ratio [OR] 1.07, 95% confidence interval [C.I.] 1.00-1.13; P = 0.044). The development and the recovery of at least one pituitary hormone deficiency were observed in 12.2% and 14.2% of patients, respectively. The risk of developing new pituitary hormone deficiencies was correlated with cavernous sinus invasion as evaluated by magnetic resonance imaging (hazard ratio [HR] 4.19, 95% C.I. 1.39-12.66; P = 0.010), whereas the probability to normalize at least one pituitary hormone deficiency was significantly correlated with younger age of patients (HR 0.27, 95% CI 0.12-0.61; P = 0.002). CONCLUSIONS: The results of this study reinforce the concept that endoscopic TNS surgery is a safe therapeutic option in the elderly patients with NFPA, even in presence of comorbidities and high anesthetic risk.

Validation of a CT-based motion model with in-situ fluoroscopy for lung surface deformation estimation.

Many surrogate-based motion models (SMMs), proposed to guide motion management in radiotherapy, are constructed by correlating motion of an external surrogate and internal anatomy during CT-simulation. Changes in this correlation define model break down. We validate a methodology that incorporates fluoroscopic (FL) images acquired during treatment for SMM construction and update. Under a prospective IRB, 4DCT scans, VisionRT (VRT) surfaces, and orthogonal FLs were collected from five lung cancer patients. VRT surfaces and two FL time-series were acquired pre- and post-treatment. A simulated annealing optimization scheme was used to estimate optimal lung deformations by maximizing the mutual information (MI) between digitally reconstructed radiographs (DRRs) of the SMM-estimated 3D images and FLs. Our SMM used partial-least-regression and was trained using the optimal deformations and VRT surfaces from the first breathing-cycle. SMM performance was evaluated using the MI score between reference FLs and the corresponding SMM or phase-assigned 4DCT DRRs. The Hausdorff distance for contoured landmarks was used to evaluate target position estimation error. For four out of five patients, two principal components approximated lung surface deformations with submillimeter accuracy. Analysis of the MI score between more than 4000 pairs of FL and DRR demonstrated that our model led to more similarity between the FL and DRR images compared to 4DCT and DRR images from a model based on an a priori correlation model. Our SMM consistently displayed lower mean and 95th percentile Hausdorff distances. For one patient, 95th percentile Hausdorff distance was reduced by 11 mm. Patient-averaged reductions in mean and 95th percentile Hausdorff distances were 3.6 mm and 7 mm for right-lung, and 3.1 mm and 4 mm for left-lung targets. FL data were used to evaluate model performance and investigate the feasibility of model update. Despite variability in breathing, use of post-treatment FL preserved model fidelity and consistently outperformed 4DCT for position estimation.

Development and prospective in-patient proof-of-concept validation of a surface photogrammetry + CT-based volumetric motion model for lung radiotherapy.

PURPOSE: We develop and validate a motion model that uses real-time surface photogrammetry acquired concurrently with four-dimensional computed tomography (4DCT) to estimate respiration-induced changes within the entire irradiated volume, over arbitrarily many respiratory cycles. METHODS: A research, couch-mounted, VisionRT (VRT) system was used to acquire optical surface data (15 Hz, ROI = 15 × 20 cm2 ) from the thoraco-abdominal surface of a consented lung SBRT patient, concurrently with their standard-of-care 4DCT. The end-exhalation phase from the 4DCT was regarded as reference and for each remaining phase, deformation vector fields (DVFs) with respect to the reference phase were computed. To reduce dimensionality, the first two principal components (PCs) of the matrix of nine DVFs were calculated. In parallel, ten phase-averaged VRT surfaces were created. Surface DVFs and corresponding PCs were computed. A principal least squares regression was used to relate the PCs of surface DVF to those of volume DVFs, establishing a relationship between time-varying surface and the underlying time-varying volume. Proof-of-concept validation was performed during each treatment fraction by concurrently acquiring 30 s time series of real-time surface data and "ground truth" kV fluoroscopic data (FL). A ray-tracing algorithm was used to create a digitally reconstructed fluorograph (DRF), and motion trajectories of high-contrast, soft-tissue, anatomical features in the DRF were compared with those from kV FL. RESULTS: For five of the six fluoroscopic acquisition sessions, the model out-performed 4DCT in predicting contour Dice coefficient with respect to fluoroscopy-derived contours. Similarly, the model exhibited a marked improvement over 4DCT for patch positions on the diaphragm. Model patch position errors varied from 5 to -15 mm while 4DCT errors ranged between 5 and -22.4 mm. For one fluoroscopic acquisition, a marked change in the a priori internal-external correlation resulted in model errors comparable to those of 4DCT. CONCLUSIONS: We described the development and a proof-of-concept validation for a volumetric motion model that uses surface photogrammetry to correlate the time-varying thoraco-abdominal surface to the time-varying internal thoraco-abdominal volume. These early results indicate that the proposed approach can result in a marked improvement over 4DCT. While limited by the duration of the fluoroscopic acquisitions as well as the resolution of the acquired images, the DRF-based proof-of-concept technique developed here is model-agnostic, and therefore, has the potential to be used as an in-patient validation tool for other volumetric motion models.

Effect of varying dose-per-pulse and average dose rate in X-ray beam irradiation on cultured cell survival.

Characterizing the biological effects of flattening filter-free (FFF) X-ray beams from linear accelerators is of importance, due to their increasing clinical availability. The purpose of this work is to determine whether in vitro cell survival is affected by the higher dose-per-pulse present in FFF beams in comparison with flattened X-ray beams. A Varian TrueBeam(®) linear accelerator was used to irradiate the T98G, V79-4 and U87-MG cell lines with a single fraction of 5 Gy or 10 Gy doses of X-rays. Beams with energies of 6 MegaVolt (MV), 6 MV FFF and 10 MV FFF were used, with doses-per-pulse as measured at the monitor chamber of 0.28, 0.78 and 1.31 mGy/pulse for 6 MV, 6 MV FFF and 10 MV FFF, respectively. The dose delivered to each Petri dish was verified by means of ionization chamber measurements. No statistically significant effects on survival fraction were observed for any of the cell lines considered, either as a function of dose-per-pulse, average dose rate or total dose delivered. Biological effects of higher instantaneous rates should not be excluded on the basis of in vitro experimental results such as the ones presented in this work. The next step toward an assessment of the biological impact of FFF beams will require in vivo studies.

Filamin A (FLNA) plays an essential role in somatostatin receptor 2 (SST2) signaling and stabilization after agonist stimulation in human and rat somatotroph tumor cells.

Somatostatin receptor type 2 (SST2) is the main pharmacological target of medical therapy for GH-secreting pituitary tumors, but molecular mechanisms regulating its expression and signaling are largely unknown. The aim of this study was to investigate the role of cytoskeleton protein filamin A (FLNA) in SST2 expression and signaling in somatotroph tumor cells. We found a highly variable expression of FLNA in human GH-secreting tumors, without a correlation with SST2 levels. FLNA silencing in human tumoral cells did not affect SST2 expression and localization but abolished the SST2-induced reduction of cyclin D1 (-37% ± 15% in control cells, P < .05 vs basal) and caspase-3/7 activation (+63% ± 31% in control cells, P < .05 vs basal). Overexpression of a FLNA dominant-negative mutant that specifically prevents SST2-FLNA binding reduced SST2 expression after prolonged agonist exposure (-55% ± 5%, P < .01 vs untreated cells) in GH3 cells. Moreover, SST2-induced apoptotic effect (77% ± 54% increase of caspase activity, P < .05 vs basal) and SST2-mediated ERK1/2 inhibition (48% ± 17% reduction of ERK1/2 phosphorylation, P < .01 vs basal) were abrogated in cells overexpressing another FLNA mutant that prevents FLNA interaction with partner proteins but not with SST2, suggesting a scaffold function of FLNA in somatotrophs. In conclusion, these data demonstrate that FLNA is involved in SST2 stabilization and signaling in tumoral somatotrophs, playing both a structural and functional role.

Cyclic adenosine 3'-5'-monophosphate (cAMP) exerts proliferative and anti-proliferative effects in pituitary cells of different types by activating both cAMP-dependent protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac).

In the pituitary the activation of cyclic adenosine 3'-5'-monophosphate (cAMP) dependent pathways generates proliferative signals in somatotrophs, whereas in pituitary cells of other lineages its effect remains uncertain. Moreover, the specific role of the two main cAMP effectors, protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac), has not been defined. Aim of this study was to investigate the effect of cAMP on pituitary adenomatous cells proliferation and to identify PKA and Epac differential involvement. We found that cAMP increased DNA synthesis and cyclin D1 expression in somatotropinomas, whereas it reduced both parameters in prolactinomas and nonfunctioning adenomas, these effects being replicated in corresponding cell lines. Moreover, the divergent cAMP effects were mimicked by Epac and PKA analogs, which activated Rap1 and CREB, respectively. In conclusion, we demonstrated that cAMP exerted opposite effects on different pituitary cell types proliferation, these effects being mediated by both Epac and PKA.

Endoscopic expanded endonasal approach: preliminary experience with the new 3D endoscope.

The recent introduction of the 3D endoscope for endonasal surgery has been welcomed because of its promise to overcome the main limitation of endoscopy, namely the lack of stereoscopic vision. This innovation particularly regarded the most complex transnasal surgery of the skull base. We therefore discuss our early experience as ENT surgeons with the use of a purely 3D endoscopic expanded endonasal approach for supradiaphragmatic lesions in 10 consecutive patients. This article will focus on the surgical technique, the complications, the outcome, and more importantly the advantages and limitations of the new device. We believe that the new 3D system shows its main drawback when surgery is conducted in the narrow nasal spaces. Nevertheless, the improved knowledge of the three-dimensional nasal anatomy enabled the ENT surgeon to perform a more selective demolition of the nasal structures even in the anterior part of the nose. The depth perception obtained with the 3D system also permitted a better understanding of the plasticity of the surgical defects, increasing the confidence to perform successful skull base plasties. We believe that, for both the ENT surgeon and the neurosurgeon, the expanded endonasal approach is the main indication for this exciting tool, although larger prospective studies are needed to determine the equality to the 2D HD endoscope in oncological terms.

Transnasal 3D endoscopic skull base surgery: questionnaire-based analysis of the learning curve in 52 procedures.

In the past decade, surgical treatment of skull base pathologies has greatly advanced through the advent of the endoscope and later of the high definition endoscope. Recently a new type of three dimensional (3D) scope has been introduced to permit the surgeon a real stereoscopic vision of the operating field and to overcome the limitations of the 2D endoscopic set up. As with all new technologies a formalized adaptation period is essential for the surgeon to secure steady outcomes and low complications. To determine the subjective difficulties that one may encounter during this sensitive period we therefore devised and analyzed a questionnaire that evaluated the first ten procedures with the 3D device of junior and senior ENT and neurosurgeons. 52 consecutive patients were treated with purely 3D transnasal endoscopy for skull base pathologies. Sensation of strain or dizziness, difficulties in anatomical orientation and difficulties in performing the surgical gesture were assessed for each surgeon. The learning curve and difficulties of junior and senior surgeons are discussed and strategies to overcome the initial problems are devised. Our results confirm that after only few procedures, the advantages of the 3D endoscopic system including better visualization and depth perception are able to outweigh the inconveniences that go hand in hand with the learning of a new skill set.

Responses to corticotrophin-releasing hormone and dexamethasone in a large series of human adrenocorticotrophic hormone-secreting pituitary adenomas in vitro reveal manifold corticotroph tumoural phenotypes.

Patients with Cushing's disease are known to present a variable secretory response to stimulatory and inhibitory challenges. Evaluation of the secretory behaviour of pituitary adrenocorticotrophic hormone (ACTH)-secreting adenomas in vitro aids in the comprehension of its behaviour in vivo; however, given the small size of these tumours and the consequent paucity of material available to in vitro studies, a comprehensive study on the secretory behaviour of human corticotroph tumours has not yet been performed. The present study aimed to assess the spectrum of responses to the two main corticotroph modulators, corticotrophin-releasing hormone (CRH) and dexamethasone, in a large series of human ACTH-secreting pituitary tumours. Seventy-two ACTH-secreting pituitary tumours were collected during surgery and established in culture. Specimens were incubated with 10 nm CRH and/or 10 nm dexamethasone for 4 h and 24 h. Secretion in unstimulated, control wells was set at 100% and changes in ACTH concentrations by at least 20% were considered as responses. Parallel experiments in 12 rat anterior pituitary primary cultures were evaluated. A marked ACTH increase was observed during incubation with CRH in 70% of tumoural specimens at 4 h (range 124-3500% of control wells) and in 57% at 24 h (range 122-3323%). Dexamethasone reduced ACTH secretion in almost 50% of tumours (range 78-2% of control at 4 h; 76-3% at 24 h), whereas it did not affect ACTH medium levels in 30% of specimens and induced a paradoxical ACTH increase in 20% of tumours (range 130-327% of control at 4 h; 156-348% at 24 h). By comparison, CRH uniformly increased ACTH levels in rat anterior pituitary primary cultures (mean 745 ± 84% at 4 h; 347 ± 25% at 24 h), whereas dexamethasone decreased ACTH levels by 40-50% in all experiments. In conclusion, the present study of a large series of human ACTH-secreting pituitary tumours in vitro revealed a considerable variability in the responses to CRH and dexamethasone. This finding indicates the existence of multiple corticotroph tumoural phenotypes and may account for the different responses to physiological and pharmacological modulators in vivo.

Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours.

Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)-release inhibitor. Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing's disease. The present study aimed to test the effect of preproTRH(178-199) in human tumoural corticotrophs. Twenty-four human ACTH-secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 nm preproTRH(178-199). ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%). Parallel experiments were performed in rat anterior pituitary primary cultures. A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 nm ppTRH: 70 +/- 4% control at 4 h and 83 +/- 5% control at 24 h; for 100 nm ppTRH: 70 +/- 4% control at 4 h and 85 +/- 5% control at 24 h), whereas a mild and short-lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens. The inhibitory effect of preproTRH(178-199) was more evident in macroadenomas and significantly correlated with sensitivity to dexamethasone inhibition. Significant inhibition of ACTH secretion by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of incubation. The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback. This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178-199) as a regulator of ACTH secretion.

Perioperative cortisol can predict hypothalamus-pituitary-adrenal status in clinically non-functioning pituitary adenomas.

BACKGROUND: Peri-operative steroids are administered routinely to patients with pituitary adenoma undergoing transsphenoidal adenomectomy (TSA). AIM: To evaluate hypothalamic-pituitary-adrenal (HPA) axis before and after programmed endoscopic TSA (E-TSA) in patients with clinically non-functioning pituitary macroadenoma (NFPA). DESIGN: Open prospective. SETTING: Tertiary referral hospitals. PATIENTS: Seventy-two consecutive patients (20-87 yr, 37 males). INTERVENTIONS: Adrenal steroid replacement therapy (ASRT) was given only in patients with hypocortisolism [08:00 h cortisol (F) <8 microg/dl]. MAIN OUTCOME MEASUREMENTS: After ETSA, achieving wide (>90%) selective resection of the adenoma in all, F and clinical picture were checked at day 2. The low-dose (1 microg) ACTH test (LDACTH) was performed at 6 weeks and repeated at 12 months. RESULTS: Hypocortisolism was present pre-operatively in 14 patients (19.4%), persisted post-operatively in all but one, and was detected de novo at the post-operative day 2 control in 6 (10.3%). In all but one the post-operative day 2 basal F and peak F during LDACTH test were concordant. No patient whose F was > 8 microg/dl was treated with ASRT or developed symptoms of adrenal failure during the follow-up (1-11 yr, median 5). CONCLUSIONS: HPA function is usually preserved in NFPA and is infrequently impaired after complete tumor removal by E-TSA. The 08:00 h. plasma cortisol evaluation before and 2 days after surgery, using as cut-off the value of 8 microg/dl, allows full evaluation of HPA status. Peri-operative steroid treatment should be given only in patients with hypocortisolism.

Interference study of the chi c0(13P0) in the reaction -pp-->pi0pi0.

Fermilab experiment E835 has observed (-)pp annihilation production of the charmonium state chi(c0) and its subsequent decay into pi(0)pi(0). Although the resonant amplitude is an order of magnitude smaller than that of the nonresonant continuum production of pi(0)pi(0), an enhanced interference signal is evident. A partial wave expansion is used to extract physics parameters. The amplitudes J=0 and 2, of comparable strength, dominate the expansion. Both are accessed by L=1 in the entrance (-)pp channel. The product of the input and output branching fractions is determined to be B((-)pp-->chi(c0))xB(chi(c0)-->pi(0)pi(0))=(5.09+/-0.81+/-0.25)x10(-7).

Estroprogestinic pill normalizes IGF-I levels in acromegalic women.

In some acromegalic patients medical treatment does not succeed in normalizing GH/IGF-I values. Data showing IGF-I suppression in acromegaly by estrogen and by tamoxifen use prompted us to reevaluate the effects of estroprogestins (EP) supplementation on GH/IGF-I levels in acromegalic women resistant or only partially sensitive to medical treatment. Eight active acromegalic women (30-52 yr, 4 with regular menses) entered a prospective open pilot study. Three of them, resistant to medical treatment, were off therapy; the remaining five, partially sensitive, maintained it at the maximally effective dosages throughout the study. Patients were treated with a triphasic pill (ethynil-estradiol 30-40-30 microg/day and desogestrel 50-70-100 mg/day) for 13 +/- 7 months. IGF-I levels fell from 512 (median, interquartile 436-657) microg/l to 282 (244-526) microg/l (p=0.0414); the decrease was observed in 6 patients (75%), and normal values were reached in 4 (50%). GH levels did not change [basal 7.6 (6.2-8.6) microg/l, final 7.6 (6.5-8.3) microg/l]. Effectiveness of treatment was not dependent on concomitant anti-GH treatment or gonadal status. In all patients IGF-I levels re-increased after EP withdrawal. This pilot study shows a marked IGF-I lowering effect of pill in acromegalic women, and warrants a prospective randomized study in patients resistant or partially sensitive to other medical treatments.

Pigment villonodular synovitis of the spine. Case report and review of the literature.

Pigmented villonodular synovitis (PVNS) is a disease of the joints which uncommonly involves the spine. We present a 70-year-old woman with radicular symptoms who was found to have a mass arising from a lumbar zygapophyseal joint with extension into the spinal canal. Following gross-total excision of the mass, histology revealed PVNS. One month after surgery, the patient had no symptoms and there was no evidence of residual or recurrent disease.

From macroprolactinoma to concomitant ACTH-PRL hypersecretion with Cushing's disease.

Multiple pituitary hormone hypersecretions have been already described, but the combination of PRL and ACTH excess is rare. This report deals with a 42-yr-old woman affected by macroprolactinoma (PRL 12,720 microg/l, huge tumor with extrasellar extension at imaging). After one year on dopaminergic treatment causing PRL normalization and tumor shrinkage, she developed hypercortisolism (UFC 1,000 microg/24 h, ACTH 200 ng/l). Cushing's disease was diagnosed. After neurosurgery (at immunocytochemistry mixed ACTH-PRL adenoma was shown) hypercortisolism remitted, whereas pathological hyperprolactinemia with tumor remnant in cavernous sinus persisted and hypopituitarism developed. The patient reported seems atypical for the following reasons: 1) the concomitant PRL and ACTH hypersecretions; 2) the clinical presentation with hypercortisolism following hyperprolactinemia; 3) the surgical cure of hypercortisolism with persisting hyperprolactinemia.

Management of medulloblastoma and ependymoma in infants: a single-institution long-term retrospective report.

To reduce the sequelae from CNS irradiation (RT), 16 children younger than 3 years with medulloblastoma-PNET (13 cases) and ependymoma (3 cases) were treated between 1987-1993 according to different postsurgical chemotherapy (CT) programs. None of these patients presented with metastases. Eleven patients were rendered disease-free by surgery, while 5 had residual tumor. Adjuvant therapy depended on patients' age, postsurgical status and parents' consent to radiotherapy (RT). Nine of the 16 infants remained alive in continuous complete remission from the first neoplasm (median follow-up 7 years). Three of them had been treated with CT alone and 6 with combined CT + RT (posterior fossa 4, whole CNS 2). Seven patients relapsed a median of 13 months after diagnosis, and all 7 of them died of their disease. Despite the omission of RT in 6 of the 16 patients and administration of only focal RT in 8 of the 16, the outcome of this series was satisfactory. Local failure (in 5/7 patients) was the major problem, despite the high dose of RT used in 2 of these 5. In 4 of 6 evaluable children school performance was satisfactory. One child in whom the entire CNS was irradiated developed glioblastoma multiforme 120 months after the first diagnosis of medulloblastoma.

Lanreotide 60 mg, a longer-acting somatostatin analog: tumor shrinkage and hormonal normalization in acromegaly.

BACKGROUND: Somatostatin analogues are nowadays the milestone in the medical treatment of acromegaly. We evaluated the effects of a new 60 mg longer-acting formulation of lanreotide (LAN60) on GH/IGF-I levels and tumor size. PATIENTS: Twenty-one acromegalics entered a prospective monocentric open study. Eight were consecutive "de novo" patients (group I). Thirteen patients sensitive to SA (GH levels < 2.5 [mgr]g/l and/or IGF-I normalization on chronic LAN 30 mg (LAN30) treatment) were switched to LAN60 (group II). PROTOCOL: LAN60 was administered IM for 6 cycles at 28 day intervals. In group I when GH/IGF-I remained pathological, the intervals were shortened to 21 days for the last three cycles. CONTROLS: GH/IGF-I at the end of the 1st, 3rd and 6th cycle; MRI at the end of the study in all patients in group I bearing an adenoma. RESULTS: Group I. GH (p = 0.00638, below 2.5 [mgr]g/l in two patients) and IGF-I (p = 0.0289, normalized in 5) significantly decreased. In one of two patients shortening the LAN60 schedule was more effective in suppressing GH/IGF-I. Group II. No change in GH and IGF-I levels was observed with the administration of LAN60, instead of LAN30. On LAN60 GH remained below 2.5 [mgr]g/l in 8/10 patients and IGF-I normal in 11/11 patients that had attained those values on LAN30. Tumor markedly shrank (23% to 64% vs basal), from 1400 (664-1680) mm3 to 520 (500-960) mm3 (median, interquartile, p = 0.0218) in all the 5 evaluable patients. CONCLUSION: LAN60 is a very effective and longer-lasting formulation for the treatment of acromegaly. A closer administration schedule might achieve greater efficacy. Its effectiveness in shrinking tumor opens new perspectives in the therapy of acromegaly.

Triventricular hydrocephalus: review of 71 cases evaluated at the Istituto Neurologico "C. Besta" Milan over the last 10 years.

The authors review 71 patients with triventricular hydrocephalus in whom a contrast-enhanced CT scan did not show any tumoral or vascular lesion that could have caused the hydrocephalus. The patients were subdivided into three age groups. The results of the neuroradiological examination, the surgical treatment, and the complications of the shunt procedure are analyzed, with special reference to the high number (13) of periaqueductal alterations of signal pattern found on MRI (interpreted as a "slow growing" neoplasm) and to the incidence and causes of shunt malfunction.