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Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and strict criteria for defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5 years and 35% at 10 years. We conducted a pooled and meta-analysis comparing recurrence rate, post-operative-complications, and survival in patients undergoing either microsurgical (MA) or endoscopic approaches (EA). Search of literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify surgical series of clivus chordomas published between January 1990 and March 2018 on Pubmed, Scopus, and Cochrane. Two different statistical analyses have been performed: a pooled analysis and a single-arm meta-analysis of overall recurrence rate and subgroup meta-analysis of complications in the subgroups open surgery and endoscopic surgery. After full-text screening, a total of 58 articles were included in the pooled analysis and 27 studies were included for the study-level meta-analysis. Pooled analysis—the extent of resection was the only association that remained significant (subtotal: HR = 2.18, p = 0.004; partial: HR = 4.40, p < 0.001). Recurrence was more prevalent among the surgical patients (45.5%) compared to endoscopic ones (23.7%). Meta-analysis—results of the cumulative meta-analysis showed an overall rate of recurrence of 25.6%. MA recurrence rate was 31.8% (99% CI 14-52.8), EA recurrence rate was 19.4% (5.4-39.2). CSF leak rate for the endoscopic group was 10.3% (99%CI 5-17.3) and 9.5% (99%CI 1.2-24.6) for the open surgery group. The partial removal versus total removal has an influence on recurrence rate (p < 0.001). MA recurrence rate was 31.8%; EA recurrence rate was 19.4%. The extent of resection is confirmed as a statistically significant factor affecting the risk for recurrence both with the pooled analysis and with the meta-analysis. Meta-analysis demonstrated that older patients tend to recur more than young patients, especially in surgical group.

The presence of coronary artery calcium (CAC0) is associated with increased cardiac-related mortality and is a common indication to initiate statin therapy to prevent future long-term cardiac-related adverse events. CAC is also well visualized on noncontrast chest computed tomography simulation (CT sim) scans used for breast radiation planning. We hypothesize that by screening for incidental CAC on CT sims, radiation oncologists could help identify patients who may benefit from additional preventive medical interventions with their primary care physician or cardiologist.A retrospective analysis of 126 consecutive patients with breast cancer treated with external beam radiation therapy at a single institution was performed. Noncontrast CT sim scans were reviewed for the presence of CAC and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) was calculated to identify patients who may benefit from initiating statin therapy. Patients with CAC0 and/or ASCVD risk20% were identified as those who may benefit from statin therapy.Out of 72 patients with CAC0, only 12(16%) had reported pre-existing coronary artery disease and 32(44%) were not already on recommended statin therapy. CAC0 visualized on CT sim was able to identify 29 additional patients who would benefit from statin beyond what the ASCVD risk calculator could identify.Observation of incidental CAC on breast radiation-planning CT scans identified patients who could benefit from cardiac-related preventive strategies. By increasing attention, awareness, and reporting of incidental CAC visible on CT sims, radiation oncologists may fulfill a unique role to bridge a potential gap in cardiovascular preventive medicine.

Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas. The therapeutic management of acromegaly always requires a personalized strategy. Normal age-matched IGF-I values are the treatment goal. Transsphenoidal surgery by an expert neurosurgeon is the primary treatment modality for most patients, especially if there are neurological complications. In patients with poor clinical conditions or who refuse surgery, primary medical treatment should be offered, firstly with somatostatin analogs (SSAs). In patients who do not reach hormonal targets with first-generation depot SSAs, a second pharmacological option with pasireotide LAR or pegvisomant (alone or combined with SSA) should be offered. Irradiation could be proposed to patients with surgical remnants who would like to be free from long-term medical therapies or those with persistent disease activity or tumor growth despite surgery or medical therapy. Since the therapeutic tools available enable therapeutic targets to be achieved in most cases, the challenge is to focus more on the quality of life.

BACKGROUND: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. OBJECTIVES: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. METHODS: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. RESULTS: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. CONCLUSIONS: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more “typical” corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas.

The transnasal approach to lesions involving the craniovertebral junction represents a technical challenge because of limited inferior exposure. The endoscopic transseptal approach (EtsA) with posterior nasal spine (PNS) removal is described. This technique can create a wide exposure of the craniovertebral junction, thereby increasing the caudal exposure.On patients undergoing anterior craniovertebral junction decompression, we calculated the degree of exposure on the sagittal plan through a paraseptal route, an EtsA without and with PNS removal. The horizontal exposure and working area with the latter approach were also evaluated.Five patients underwent the transnasal procedure. The age of patients ranged from 34-71 years. All patients harbored basilar impression. The mean postoperative Nurick grade (1, 8) was improved versus the average preoperative grade (3). The average follow-up duration was 16 months. All patients underwent occipitocervical fixation. The mean vertical distances, from the clinoid recess to the inferior most limit with the paraseptal approach, EtsA without and with PNS removal were 38.52, 44.12, and 51.16 mm, respectively. The difference between our approach and a standard paraseptal route was statistically significant (P = 0.041; P0.05). The mean horizontal distances were 31.68 mm (mononostril entry) and 35.37 mm (binostril entry). The mean working area was 1795.53 mmEndoscopic endonasal approaches to the craniovertebral junction are increasing, but the downward extension on the anterior cervical spine represents a limit. Therefore, many surgeons prefer transoral or transcervical approaches. The EtsA with PNS removal allows for a more caudal exposure than the standard paraseptal approach, with reduced nasal trauma.

Background Optimal vision and ergonomics are important factors contributing to achievement of good results during neurosurgical interventions. The operating microscope and the endoscope have partially filled the gap between the need for good surgical vision and maintenance of a comfortable posture during surgery. Recently, a new technology called video-assisted telescope operating monitor or exoscope has been used in cranial surgery. The main drawback with previous prototypes was lack of stereopsis. We present the first case report of cranial surgery performed using the VITOM 3D, an exoscope conjugating 4K resolution view and three-dimensional technology, and discuss advantages and disadvantages compared with the operating microscope. Case Description A 50-year-old patient with vertigo and headache linked to a petrous ridge meningioma underwent surgery using the VITOM 3D. Complete removal of the tumor and resolution of symptoms were achieved. The telescope was maintained over the surgical field for the duration of the procedure; a video monitor was placed at 2 m from the surgeons; and a control unit allowed focusing, magnification, and repositioning of the camera. Conclusions VITOM 3D is a video system that has overcome the lack of stereopsis, a major drawback of previous exoscope models. It has many advantages regarding ergonomics, versatility, and depth of field compared with the operating microscope, but the holder arm and the mechanism of repositioning, refocusing, and magnification need to be ameliorated. Surgeons should continue to use the technology they feel confident with, unless a distinct advantage with newer technologies can be demonstrated.

ACTH-secreting pituitary tumors are by definition partially autonomous, i.e., secrete ACTH independent of physiological control. However, only few, small-sized studies on proopiomelanocortin (POMC) and its regulation by corticotropin-releasing hormone (CRH) or glucocorticoids are available. Objective of the present study was to report on constitutive and CRH- and dexamethasone-regulated POMC, CRH (CRH-R1), and glucocorticoid receptor (NR3C1) gene expression in a large series of human corticotrope adenomas. Fifty-three ACTH-secreting adenomas were incubated with 10 nM CRH or 10 nM dexamethasone for 24 h. POMC, CRH-R1, NR3C1, and its alpha and beta isoforms were quantified and medium ACTH measured. Constitutive POMC expression proved extremely variable, with macroadenomas exhibiting higher levels than microadenomas. POMC increased during CRH in most specimens; conversely, changes induced by dexamethasone were varied, ranging from decrease to paradoxical increase. No correlation between POMC and ACTH was detected in any experimental condition. CRH-R1 expression was not linked to the response to CRH while NR3C1 was expressed at greater levels in specimens who failed to inhibit during dexamethasone; glucocorticoid receptor α was the more abundant isoform and subject to down-regulation by dexamethasone. Our results demonstrate a considerable variability in POMC expression among tumors and no correlation between POMC and ACTH, suggesting that POMC peptide processing/transport plays a major role in modulating ACTH secretion. Further, CRH-R1 and NR3C1 expression were not linked to the expected ligand-induced outcome, indicating that receptor signaling rather than abundance determines corticotrope responses. Our findings pave the way to new avenues of research into Cushing’s disease pathophysiology. Electronic supplementary material The online version of this article (doi:10.1007/s12020-016-0990-x) contains supplementary material, which is available to authorized users.

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.

Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.

Summary background Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH–IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking. design Prospective open trial. patients In 19 acromegalic patients with active disease (34–82 years old, seven males, 12 females) resistant to chronic (9–12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved ‘safe’ GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 µg/l (range 16–60 µg/l; 1 µg = 21·2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients. results The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1–3·5 mg/week), decreased GH from 6·6 ± 0·9 to 4·6 ± 0·6 µg/l (P = 0·018), and IGF-I from 552 ± 44 to 428 ± 54 µg/l (P = 0·019) after 6 months (median, range 3–18 Months). Combined treatment decreased GH to < 2·5 µg/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (−49 ± 7%, and −47 ± 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 ± 8% in four, and IGF-I by 35–38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated. conclusions The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.

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.

Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training.Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback.All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible achievable score where the evaluator strongly agreed with the proposed factor). Individual components had scores at or above 80% (except for 1). The only score that was below 80% was related to radiographic visibility of the model for adequate surgical planning (score of 74%). The highest score was given to usefulness in neurosurgical training (98%).The skull base tumor model is an effective tool to provide more practice in preoperative planning and technical skills.

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 n. m 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 n. m ppTRH: 70 ± 4% control at 4 h and 83 ± 5% control at 24 h; for 100 n. m 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. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd.

Kilovoltage x-ray projection images (kV images for brevity) are increasingly available in image guided radiotherapy (IGRT) for patient positioning. These images are two-dimensional (2D) projections of a three-dimensional (3D) object along the x-ray beam direction. Projecting a 3D object onto a plane may lead to ambiguities in the identification of anatomical structures and to poor contrast in kV images. Therefore, the use of kV images in IGRT is mainly limited to bony landmark alignments. This work proposes a novel subtraction technique that isolates a slice of interest (SOI) from a kV image with the assistance of a priori information from a previous CT scan. The method separates structural information within a preselected SOI by suppressing contributions to the unprocessed projection from out-of-SOI-plane structures. Up to a five-fold increase in the contrast-to-noise ratios (CNRs) was observed in selected regions of the isolated SOI, when compared to the original unprocessed kV image. The tomographic image via background subtraction (TIBS) technique aims to provide a quick snapshot of the slice of interest with greatly enhanced image contrast over conventional kV x-ray projections for fast and accurate image guidance of radiation therapy. With further refinements, TIBS could, in principle, provide real-time tumor localization using gantry-mounted x-ray imaging systems without the need for implanted markers.

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) 90%) selective resection of the adenoma in all, F and clinical picture were checked at day 2. The low-dose (1 µg) 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 µg/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 µg/dl, allows full evaluation of HPA status. Peri-operative steroid treatment should be given only in patients with hypocortisolism.

Between 1956 and 1987 operations were performed on 36 patients below the age of 20 years for epidermoid and dermoid cysts of the central nervous system. Seventeen tumors were intracranial intradural lesions (47%): 12 were located in the supratentorial region (71%) and 5 were located in the infratentorial region (29%). Ten of these tumors (59%) were seated along the midline structures. The clinical presentation was consistent with the location of the tumors. The neuroradiological diagnosis was mostly made with the aid of pneumoencephalography, computed tomography (CT), nonionic contrast medium CT cisternography, and magnetic resonance imaging. Complete removal of the tumor contents was performed in all cases but one, although the completeness of removal of the tumor capsule could not be exactly estimated in some patients. At late follow-up only two tumor recurrences were observed. Radical removal of the tumor capsule of these congenital tumors, even when it is connected to vital neurovascular structures, seems advisable in patients who become symptomatic within the first two decades of life.

Neurosurgery is regarded as the first-line treatment of acromegaly. Because of its low cure rate in macro and invasive adenoma, the role of primary medical treatment is debated.Our objective was to evaluate primary pharmacological treatment in acromegaly.We conducted an open prospective study at two Italian tertiary level centers.We studied 67 consecutive patients (36 women; age, 54.9 +/- 14.2 yr; 72% bearing macroadenoma).Individually tailored octreotide LAR (OCLAR) was administered.Outcomes included safe GH (2.5 mug/liter), normal age-matched IGF-I levels, and tumor shrinkage.After a median follow-up of 48 months (range, 6-108 months), safe GH levels and normal age-matched IGF-I values were obtained by 68.7 and 70.1% of patients, respectively. Hormonal endpoints were achieved regardless of basal levels, and early results were predictive of outcome. Tumor shrank in 82.1% of patients by 62 +/- 31% (range, 0-100%), decreasing from 2101 +/- 2912 to 1010 +/- 2196 mm(3) (P0.0001). The higher the basal GH values and the greater the GH/IGF-I changes on treatment, the greater the tumor shrinkage. Tumor disappeared in three patients and was progressively reduced to empty sella in five patients; apparent magnetic resonance imaging cavernous sinus invasion disappeared in three. In males, testosterone increased, restoring eugonadism in 64% of hypogonadal patients.The efficacy on GH/IGF-I levels in unselected patients and the outstanding volumetric control indicate that treatment with OCLAR may be the first therapeutic approach to all acromegalic patients not amenable to surgical cure. Tumor shrinkage might also encourage the evaluation of primary OCLAR adoption in patients with initial visual field defects.

Context: Surgery is a cornerstone in the treatment of acromegaly, but its efficacy in large, invasive tumors is scant. Objective: The objective of this study was to investigate whether partial surgical removal of GH-secreting pituitary tumors enhances the response rate to somatostatin analogs (SSA; sc octreotide, slow-release octreotide, and lanreotide). Design: This was a multicenter, open, retrospective study. Setting: The study was performed at university hospitals. Subjects and Methods: Eighty-six patients (42 women and 44 men; age, 42 ± 14 yr) with acromegaly were studied. Interventions: Patients underwent two courses of octreotide, lanreotide, or slow-release octreotide treatments before and after surgery of at least 6 months. Main Outcome Measure: The main outcome measure was normal IGF-I levels for age. Results: Presurgical SSA treatment significantly decreased GH and IGF-I levels in all patients. GH levels were less than 2.5 μg/liter in 12 patients (14%); IGF-I levels normalized in nine (10%). After surgery, GH and IGF-I levels further decreased in all patients; tumor removal was greater than 75% in 50 (58%), 50.1–75% in 21 (24%), 25.1–50% in 10 (12%), and less than 25% in five patients (6%). Preoperatively, pituitary function was impaired in 12 patients (14%). Postsurgical SSA treatment lowered GH levels to less than 2.5 μg/liter in 49 (56%) and normalized IGF-I levels in 48 patients (55%). The success rate was significantly increased compared with that before surgery (P < 0.0001). GH (r = −0.48; P < 0.0001) and IGF-I levels (r = −0.38; P = 0.0003) after postsurgery SSA treatment correlated with the amount of tumor surgically removed. After surgery, pituitary function was impaired in 28 patients (32.6%) and was improved in 12 patients (13.9%). The cumulative prevalence of pituitary deficiency did not change during the study (normal function from 40 to 42%; deficiency from 60 to 58%). Conclusions: Surgical tumor removal (>75%) enhances the response to SSAs without impairing pituitary function. Our data indicate that surgical debulking has a significant place in the treatment algorithm of acromegaly.

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.

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.

The effects of a very prolonged treatment with octreotide (OC)-long-acting repeatable (LAR) were retrospectively evaluated in 110 patients with acromegaly, showing a GH/IGF-I decrease of at least 20% vs. baseline after a short-term (6-month) OC-LAR challenge. OC-LAR was given (20 mg, im, every 28 d for 3 injections, then individually tailored) as adjuvant treatment (AT) in 59. The other 51 [primary treatment (PT)] were naive or previously treated by pharmacotherapy. IGF-I normalized in 83 patients [75%; from 770 +/- 26 (mean +/- SE) to 276 +/- 15 micro g/liter; P < 0.0001; median follow-up, 30 months; range, 18-54 months). A progressive increase in the rate of IGF-I normalization was observed. GH fell to less than 2.5 micro g/liter in 72% and to less than 1 micro g/liter in 27% (from 20.7 +/- 2.4 to 2.2 +/- 0.2 micro g/liter; P < 0.0001). PT and AT patients achieved similar final GH/IGF-I levels and rates of normalization. Patients attaining safe GH and normal IGF-I had GH levels below 5 micro g/liter after 3 months and IGF-I levels below 550 micro g/liter after 6 months. No tachyphylaxis was observed. The up-titration to 30 mg improved IGF-I suppression. Elderly patients had greater sensitivity. Tumor shrank in 46% of assessable patients, in 77% of PT patients, and in 91% of naive patients. The powerful suppression of GH/IGF-I levels without tachyphylaxis, the finding of progressive increase in the rate of IGF-I normalization and of superimposable effects in PT and AT patients, and the predictive value of short-term results support the role of PT of acromegaly with OC-LAR in at least some patients.

OBJECTIVE AND IMPORTANCE: Shunt catheter migration is a potential complication of cerebrospinal fluid shunting procedures. We report an unusual case of proximal shunt migration into the sphenoid sinus. To our knowledge, there have been no previous reports of shunt migration through the bony structures of the cranial base. CLINICAL PRESENTATION: A 41-year-old man who had had a cyst-to-peritoneum shunt placed 21 years earlier for a temporal lobe arachnoid cyst presented with cerebrospinal fluid rhinorrhea. Neuroradiological imaging revealed migration of the shunt catheter through the medial wall of the middle temporal fossa into the sphenoid sinus. INTERVENTION: The patient underwent shunt removal and repair of the dural defect. Intraoperatively, the proximal catheter tip was found in the sphenoid sinus with dural and bony erosion. The patient made an uneventful recovery. CONCLUSION: We present a unique long-term complication associated with intracranial shunt catheters. We hypothesize that excessive proximal catheter length and chronic cerebrospinal fluid pulsations contributed to migration of the catheter into the sphenoid sinus.

OBJECTIVE To assess the role that neuronavigation plays in assisting endoscopic transsphenoidal reoperations for recurrent pituitary adenomas. METHODS During a 45-month period, 19 endoscopic endonasal transsphenoidal reoperations were performed for recurrent pituitary adenomas. In 11 of 19 patients, the procedure was performed with the aid of an optically guided system. Clinical records were reviewed retrospectively, with attention to the following: comparison of baseline clinical data, the duration of surgery, and the postoperative course and complications of both image-guided and non-image-guided endoscopic reoperations. In addition, to test the reliability of the neuronavigation system, we made measurements of intraoperative accuracy in five additional transnasal endoscopic procedures in “virgin” noses and sphenoidal sinuses. RESULTS In both groups studied, we found no difference with regard to either morbidity or mortality, which were null. The mean setup time was 13 minutes shorter in non-image-guided procedures (P = 0.021), and the operative time was 36 minutes shorter in image-guided procedures (P = 0.038). No other statistically significant differences were found between the two groups. In all cases, we found that the system performed without malfunction. Continuous information regarding instrument location and trajectory was provided to the surgeon. Measurements of the intraoperative accuracy in the axial, coronal, and sagittal planes indicated a mean intraoperatively verified system error of 1.6 ± 0.6 mm. CONCLUSION Neuronavigation can be applied during endonasal transsphenoidal endoscopic surgery and requires a minimal amount of time. It makes reoperation easier, faster, and probably safer.

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.

Eighty children who in the first 2 years of life had signs and symptoms relating to a cerebral neoplasm were studied over an 18-year period (1970–1987), the mean follow-up being 8.2 years. In each case age at onset, clinical presentation, tumor location and pathological diagnosis, extent of surgical resection, postoperative mortality, adjuvant therapy length of survival and quality of life were assessed. Supratentorial tumors (59%) were more common than infratentorial. The most frequent clinical presenting feature (70%) was increased intracranial pressure. Sixty-three patients (79%) were operated on and in all of these cases a histological diagnosis was obtained. Astrocytomas (41%) and medulloblastomas (20%) were the most common oncotypes. Surgical mortality was 17.4% and the 5-year survival rate was 54%. Quality of life was assessed for all long-term surviving patients using a specifically designed protocol. Normal physical and intellectual performances were found in 46% of cases, and all together 75% of the patients had sufficient autonomy in daily life. The prognosis is more closely related to tumor location and type of treatment than to histological diagnosis or age at onset.

A patient harboring multiple hereditary exostoses with a long-lasting tetraparesis owing to intraspinal osteochondroma is described. The results of surgical treatment were poor in contrast to the results achieved by other previous authors performing decompression of the spinal cord. The related literature is briefly reviewed and conclusions are drawn in favor of computed tomographic examination of the spine of patients with vertebral complaints.

We describe here a case of holocord subependymoma in an adolescent patient, completely removed with two surgical procedures. We discuss the histological features, the diagnostic difficulties and the surgical techniques used in this case.

Twenty-four cases of supratentorial primary arachnoid cysts operated with different techniques are reviewed: both cyst shunting or extirpation may lead to a good early clinical result, but the former is less dangerous and more indicated in a particular group of patients; late results are better in the shunted patients. CT scan is almost always diagnostic and is mandatory postoperatively to assess the late results.

Long-term results (average follow-up, 9.3 years) obtained in 1000 consecutive patients suffering from cryptogenetic (“essential”) trigeminal neuralgia treated with percutaneous thermorhizotomy are analyzed. Pain relief was obtained in 95% of the treated patients. Permanent morbidity was as follows: masseter weakness in 105 patients; oculomotor palsies in 5 patients; weakening of the corneal reflex in 197 patients, 6 of whom requested an ocular operation for keratitis; and painful dysesthesia in 52 patients, 15 of whom developed a painful anesthesia syndrome. There was a recurrence rate of 18.1%, and a correlation between postoperative sensory deficit and the cure rate was found. These results are discussed and compared to the results obtained with different techniques.

The long-term results obtained in a series of 174 patients operated on for spinal meningiomas are critically analyzed. This series was similar to those of other authors with regard to age, sex, location of the tumors, and clinical presentation. Before surgery, about 70% of the patients were included in Groups I and II (mild neurological impairment), and about 30% of the patients were classified in Groups III and IV (significant to severe neurological impairment, up to paraplegia). Complete tumor removal was achieved in 96.5% of the patients, and surgical mortality was about 1%. Microsurgical technique, which was adopted in the last 29 cases, proved to be very effective in reducing undue damage to the spinal cord and in minimizing the postoperative neurological deficits. Of the 174 patients who underwent surgery, 156 underwent late follow-up study for an average of 15 years (2 patients died in the immediate postoperative period, and 16 patients were lost to follow-up). Twenty-nine patients died of causes unrelated to the spinal meningioma; of the remaining 126 patients, 92% were categorized in Groups I and II, and only 8% in Groups III and IV. The rate of recurrence was 6% (9 patients) among the 150 patients who had complete tumor removal, and the rate of regrowth was 17% (1 patient with anaplastic meningioma) among the 6 patients treated by subtotal removal. The early diagnosis of the disease and the use of microsurgical technique appeared as the most relevant factors for further improvement of the surgical results.