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Pituitary adenomas with significant extension beyond the sellar boundary, large size, asymmetrical shape and subarachnoid space invasion, although rare, represent a therapeutic challenge. The invasiveness of the tumor itself often limits the potential for complete tumor resection and increases the likelihood of intraoperative or postoperative complications, regardless of the approach. The extended endoscopic endonasal approach has been proposed as a valid alternative to the transcranial route for the treatment of certain pituitary adenomas not suitable to the standard transsphenoidal approach. Thanks to the wide and close up view provided by the endoscope via the appropriate expanded bone removal at the skull base, this technique offers, in an adequate working space, a safe exposure of the tumor and surrounding anatomical structures, at the supra-, para-, and retro-sellar areas. It stands clear that the primary goal of this approach remains the maximum allowed resection with preservation of neurological and endocrine functions. Herein, we debate the extended endoscopic endonasal technique for the treatment of pituitary adenomas, with the aim of underlying its indications, pitfalls, advantages, and limitations.

Purpose: Pituitary macroadenoma consistency can influence the ease of lesion removal during surgery, especially when using a transsphenoidal approach. Unfortunately, it is not assessable on standard qualitative MRI. Radiomic texture analysis could help in extracting mineable quantitative tissue characteristics. We aimed to assess the accuracy of texture analysis combined with machine learning in the preoperative evaluation of pituitary macroadenoma consistency in patients undergoing endoscopic endonasal surgery., Methods: Data of 89 patients (68 soft and 21 fibrous macroadenomas) who underwent MRI and transsphenoidal surgery at our institution were retrospectively reviewed. After manual segmentation, radiomic texture features were extracted from original and filtered MR images. Feature stability analysis and a multistep feature selection were performed. After oversampling to balance the classes, 80% of the data was used for hyperparameter tuning via stratified 5-fold cross-validation, while a 20% hold-out set was employed for its final testing, using an Extra Trees ensemble meta-algorithm. The reference standard was based on surgical findings., Results: A total of 1118 texture features were extracted, of which 741 were stable. After removal of low variance (n = 4) and highly intercorrelated (n = 625) parameters, recursive feature elimination identified a subset of 14 features. After hyperparameter tuning, the Extra Trees classifier obtained an accuracy of 93%, sensitivity of 100%, and specificity of 87%. The area under the receiver operating characteristic and precision-recall curves was 0.99., Conclusion: Preoperative T2-weighted MRI texture analysis and machine learning could predict pituitary macroadenoma consistency.

Background: The sellar barrier concept reflects the association between the components of the roof of the pituitary fossa and the risk of intraoperative cerebrospinal fluid (CSF) leak in the surgery of pituitary adenomas. We based our concept in previous reports on the microsurgical anatomy of the pituitary fossa's superior wall. However, proof of the usefulness of this concept in endoscopic approaches is yet missing. The aim of this study was to describe the endoscopic anatomy of the sellar barrier and its subtypes in a laboratory setting and to provide evidence of its clinical usefulness., Methods: We provided anatomical models in six fresh-frozen head and neck specimens. We performed an endoscopic endonasal approach and recreated a pathological model of each possible subtype of sellar barrier. To demonstrate the usefulness of this model in clinical practice, we conducted a prospective study including all patients with pituitary adenoma operated by an endoscopic approach between June and July 2019., Results: We successfully recreated the models for each subtype of sellar barrier. When analyzing the clinical cases, we found that intraoperatively, 73.69% (14) had a strong sellar barrier; 21.05% (4) had mixed sellar barrier, and 5.26% (1) had weak sellar barrier. We recorded one case of intraoperative CSF leak in a patient with a weak sellar barrier by magnetic resonance imaging., Conclusion: We described the endoscopic anatomy of the sellar barrier and we recreated the three subtypes in anatomical models. We also identified these subtypes in a series of clinical cases, proving its clinical usefulness., (© 2020 Wiley Periodicals, Inc.)

Purpose: Pituitary adenomas are among the most frequent intracranial tumors. They may exhibit clinically aggressive behavior, with recurrent disease and resistance to multimodal therapy. The ki-67 labeling index represents a proliferative marker which correlates with pituitary adenoma aggressiveness. Aim of our study was to assess the accuracy of machine learning analysis of texture-derived parameters from pituitary adenomas preoperative MRI for the prediction of ki-67 proliferation index class., Methods: A total of 89 patients who underwent an endoscopic endonasal procedure for pituitary adenoma removal with available ki-67 labeling index were included. From T2w MR images, 1128 quantitative imaging features were extracted. To select the most informative features, different supervised feature selection methods were employed. Subsequently, a k-nearest neighbors (k-NN) classifier was employed to predict macroadenoma high or low proliferation index. Algorithm validation was performed with a train-test approach., Results: Of the 12 subsets derived from feature selection, the best performing one was constituted by the 4 highest correlating parameters at Pearson's test. These all showed very good (ICC ≥ 0.85) inter-observer reproducibility. The overall accuracy of the k-NN in the test group was of 91.67% (33/36) of correctly classified patients., Conclusions: Machine learning analysis of texture-derived parameters from preoperative T2 MRI has proven to be effective for the prediction of pituitary macroadenomas ki-67 proliferation index class. This might aid the surgical strategy making a more accurate preoperative lesion classification and allow for a more focused and cost-effective follow-up and long-term management.

Pituitary tumors are a heterogeneous group of lesions (usually benign) and proper understanding of the anatomy, physiology, and pathology of the hypothalamic/pituitary region is essential to make an accurate diagnosis and define the essential treatment options (i.e., surgery, medical therapies, and radiotherapy, alone or in combination). Surgery is the primary treatment for acromegaly, Cushing disease, thyroid-stimulating hormone-secreting adenomas, resistant prolactinomas, and nonfunctioning pituitary adenomas causing mass effect. Medical and radiation therapy are reserved in cases in which surgery is not possible or does not provide a complete cure. In the last decades, tremendous innovations (i.e., targeted drugs and refined surgical tools and techniques) have expanded the treatment strategies for pituitary adenomas. We herein report the current indications for and depiction of the surgical techniques in pituitary surgery, review current medical treatments, and provide a glimpse of future possibilities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented. Thus, we decided to perform a multicenter study among Italian neurosurgical centers performing pituitary surgery to provide an actual depiction from the neurosurgical standpoint., Methods: On behalf of the SINch (Società Italiana di Neurochirurgia), a survey was undertaken with the participants to explore the activities in the field of pituitary surgery within 41 public institutions., Results: Of the 41 centers, 37 participated in the present study. The total number of neurosurgical procedures performed in 2016 was 1479. Most of the procedures were performed using the transsphenoidal approach (1320 transsphenoidal [1204 endoscopic, 53 microscopic, 53 endoscope-assisted microscopic] vs. 159 transcranial). A multidisciplinary tumor board is convened regularly in 32 of 37 centers, and a research laboratory is present in 18 centers., Conclusions: Diagnosing pituitary/hypothalamus disorders and treating them is the result of teamwork, composed of several diverse experts. Regarding neurosurgery, our findings have confirmed the central role of the transsphenoidal approach, with preference toward the endoscopic technique. Better outcomes can be expected at centers with a multidisciplinary team and a full, or part of a, residency program, with a greater surgical caseload., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Currently, there is no prioritization scale available to distinguish those patients with pituitary tumors who require urgent surgical intervention from those who are candidates for elective treatment., Objective: To develop a classification system that can help primary care physicians, endocrinologists, neurosurgeons, ancillary support staff, and hospital administrators identify high-priority surgical candidates., Methods: An expert international panel of clinicians consisting of endocrinologists and neurosurgeons who are involved in the diagnosis and management of sellar disease was convened. The panel retrospectively reviewed individual experiences, including a cohort of patients operated upon for pituitary related disease at the Brigham and Women's Hospital from January 2008 to November 2015. A risk stratification schema was developed to streamline patient care pathways., Results: We identified 4 groups of surgical candidates with varying levels of risk, and then assigned treatment timelines and different differential diagnoses to each. The 4 groups were as follows: group A: urgent-immediate; group B: prompt-initiate treatment within 1 to 2 weeks; group C: soon-initiate treatment within 3 months; group D: elective-as soon as indicated. Among 472 patients treated at Brigham and Women's Hospital for pituitary adenomas, each was assigned to 1 of the 4 predetermined subgroups: group A, 6.8%; group B, 30.1%; group C, 31.1%; group D, 32.0%., Conclusions: We developed a risk stratification schema that may serve as a platform to streamline care to the patients at highest risk. The expert opinions presented provide a basis for future studies regarding the risk prioritization of patients., (Copyright © 2017 by the Congress of Neurological Surgeons)

The aim of the study was to assess incidence rate, hormonal activity, and local invasiveness and evaluate outcomes of so-diagnosed atypical pituitary adenomas that underwent endoscopic endonasal surgery at the Division of Neurosurgery of Università degli Studi di Napoli Federico II. According to the 2004 WHO classification, atypical pituitary adenomas are defined by an invasive growth, Ki-67/MIB-1 proliferative index greater than 3 %, high p53 immunoreactivity, and increased mitotic activity. A retrospective analysis of a series of 434 pituitary adenomas that underwent endoscopic endonasal surgery at our department between March 2007 and February 2013 was performed. Fifty adenomas (11.5 %) met the criteria of diagnosis of atypical lesions; 10 (21.6 %) of the 50 patients were recurrent tumors with a previous transsphenoidal surgery. Forty-one (82 %) were macroadenomas, and 21/50 (42 %) showed a clear invasion of the cavernous sinus. Histotype of atypical adenomas figured out to be nonfunctioning in 23 cases (46 %), PRL secreting in 10 cases (20 %), ACTH secreting and GH secreting each apart in 8 patients (16 %), and in a single case a GH/PRL secreting adenoma (2 %). The Ki-67 labeling index ranged from 3.5 to 22.5 % (mean 5.6 %). Tumor recurrence was observed in six cases (12 %) after a mean time of 18 months (range 9-24 months). Mean follow-up was 36.5 months (range 2-80 months). Atypical pituitary adenomas account for ca. 10 % of all pituitary adenomas; these lesions have peculiar features. It should be considered that a strong immunopositivity of p53 and higher Ki-67 LI could predict an increased risk of tumor recurrence, but more studies and larger series are expected to confirm and enlarge the diagnostic and therapeutic management process of these lesions.

The management of giant and large pituitary adenomas with wide intracranial extension or infrasellar involvement of nasal and paranasal cavities is a big challenge for neurosurgeons and the best surgical approach indications are still controversial. Endoscopic extended endonasal approaches have been proposed as a new surgical technique for the treatment of such selected pituitary adenomas. Surgical series coming from many centers all around the world are flourishing and results in terms of outcomes and complications seem encouraging. This technique could be considered a valid alternative to the transcranial route for the management of giant and large pituitary adenomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Pituitary surgery is a continuous evolving specialty of the neurosurgeons' armamentarium, which requires precise anatomic knowledge, technical skills, and integrated culture of the pituitary pathophysiology. Actually it cannot be considered only from a technical standpoint, but rather a procedure resulting from the close cooperation among different specialists (e.g., ophthalmologists, neuroradiologists, endocrinologists, neurosurgeons, otorhinolaryngologists, anesthesiologists, neurophysiologists, pathologists, instrument manufacturers)., Methods: The "pure" endoscopic endonsal surgery is a procedure performed through the nose, with the endoscope alone throughout the whole approach and without any transsphenoidal retractor. The procedure consists of three main aspects: exposure of the lesion, removal of the relevant pathology, and reconstruction, going through three different steps, the nasal, the sphenoid, and the sellar phases., Conclusions: The endoscopic approach offers some advantages due to the endoscope itself: a superior close-up view of the relevant anatomy and an enlarged working angle are provided with an increased panoramic vision inside the surgical area. Concerning results in terms of mass removal, relief of clinical symptoms, cure of the underlying disease, and complication rate, these are, at least, similar to those reported in the major microsurgical series, but patient compliance is by far better. Besides the advantages to the patients, the surgeons-because of the wider and closer view of the surgical target area and the increase of the scientific activity as from the peer-reviewed literature on the topic in the past 10 years, the smoothing of interdisciplinary cooperation-, and the institutions (shorter postoperative hospital stay and increase of the case load)- the adoption of endoscopy in transsphenoidal surgery has gained a strong foothold., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Pituitary surgery is a continuously evolving specialty of neurosurgery that requires precise anatomical knowledge, technical skills, and an integrated appreciation of pituitary pathophysiology. It involves close cooperation between different specialists, i.e., the endocrinologist, neurosurgeon, neuroradiologist, pathologist, ophthalmologist, and others. It is currently possible to manage many of the different pituitary syndromes with more than one option, including medical, surgical, and radiotherapeutic options, either alone or in various combinations. In recent decades, the transsphenoidal midline route became the standard approach to the pituitary area, this being a less traumatic direct route to the sella, avoiding brain retraction and providing excellent visualization, with a lower morbidity and mortality rate as compared to transcranial procedures. Most pituitary adenomas can be managed and removed through a standard transsphenoidal approach, either microscopic or endoscopic. More recently, the introduction of the endoscope in the extended endoscopic endonasal approach has become more widespread. Here we report current indications and give a step-by-step account of the surgical techniques used in pituitary surgery, focusing on the "dangerous keypoints". We also describe possible complications of each kind of procedure., (© 2014 Elsevier B.V. All rights reserved.)

Objective: The nature of the pituitary adenomas itself exposes the possibility of a recurrence of the tumor. The aim of this study was to evaluate the effectiveness of the endoscopic endonasal transsphenoidal approach for the removal of recurrent and residual pituitary adenomas, already treated by a microscopic or endoscopic transsphenoidal approach or by a transcranial route., Methods: A total of 59 adult patients with a recurrent or regrowing pituitary adenoma underwent surgery using a pure endoscopic endonasal transsphenoidal approach. Of these patients, 31 were previously operated on by a microsurgical transsphenoidal approach, 22 by means of an endoscopic transsphenoidal route, and 6 via a transcranial route. The patient series has been divided into 3 tiers according to the primary surgery, and the results were evaluated accordingly., Results: Gross total removal was achieved in 37 of our cases (62.7%). According to prior surgery at primary disease, we found that in the subgroup of patients who underwent a microsurgical transsphenoidal approach we achieved gross total removal in 23 cases (74.2%; 23 of 31), whereas in the group of patients who underwent the endoscopic endonasal approach, gross total removal was attained respectively in 13 cases (59.1%; 13 of 22) and in only 1 case of those who underwent the transcranial approach (16.7%; 1 of 6). Postoperative complications included 1 case (1.7%) of cerebrospinal fluid leak and meningitis, and 1 with an hematoma in the tumor field (1.7%); both needed surgical reoperation., Conclusions: The endoscopic endonasal approach is a safe and effective procedure for the management of recurrent and/or regrowing pituitary tumors previously treated by either a microsurgical or an endoscopic approach., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Object: Whereas most pituitary adenomas are removable via the transsphenoidal approach, certain cases, such as dumbbell-shaped or suprasellar adenomas and recurrent and/or fibrous tumors, remain difficult to treat. The authors present their experience with the extended endoscopic endonasal approach to the suprasellar area in managing this subset of tumors, which are classically treated through a transcranial route., Methods: From June 1997 to December 2008, 615 patients underwent endoscopic endonasal transsphenoidal surgery for pituitary adenomas in the Department of Neurosurgery of the Università degli Studi di Napoli Federico II. Of this group, 20 patients with pituitary adenomas needed an extended endoscopic endonasal transtuberculum/transplanum approach for tumor removal. Two surgical corridors were used during the transsphenoidal approach: 1) the conventional endosellar extraarachnoidal corridor and 2) a suprasellar transarachnoidal corridor., Results: The extent of resection was gross total in 12 (60%) of the 20 patients, near total in 4 (20%), subtotal in 3 (15%), and partial in 1 (5%). Postoperative CSF leakage occurred in 1 patient. One patient experienced worsening of temporal hemianopsia., Conclusions: The authors' initial results with the extended endoscopic approach to the suprasellar area for selected pituitary adenomas are promising and may justify a widening of the current classical indications for transsphenoidal surgery.

Object: In addition to difficulties with anesthetic and medical management, transsphenoidal operations in patients with longstanding acromegaly are associated with inherent intraoperative challenges because of anatomical variations that occur frequently in these patients. The object of this study was to review the overall safety profile and anatomical/technical challenges associated with transsphenoidal surgery in patients with acromegaly., Methods: The authors performed a retrospective analysis of 169 patients who underwent endoscopic transsphenoidal operations for growth hormone-secreting adenomas to assess the incidence of surgical complications. A review of frequently occurring anatomical challenges and operative strategies employed during each phase of the operation to address these particular issues was performed., Results: Of 169 cases reviewed, there was no perioperative mortality. Internal carotid artery injury occurred in 1 patient (0.6%) with complex sinus anatomy, who remained neurologically intact following endovascular unilateral carotid artery occlusion. Other complications included: significant postoperative epistaxis (5 patients [3%]), transient diabetes insipidus (5 patients [3%]), delayed symptomatic hyponatremia (4 patients [2%]), CSF leak (2 patients [1%]), and pancreatitis (1 patient [0.6%]). Preoperative considerations in patients with acromegaly should include a cardiopulmonary evaluation and planning regarding intubation and other aspects of the anesthetic technique. During the nasal phase of the transsphenoidal operation, primary challenges include maintaining adequate visualization and hemostasis, which is frequently compromised by redundant, edematous nasal mucosa and bony hypertrophy of the septum and the nasal turbinates. During the sphenoid phase, adequate bony removal, optimization of working space, and correlation of imaging studies to intraoperative anatomy are major priorities. The sellar phase is frequently challenged by increased sellar floor thickness, distinct patterns of tumor extension and bony invasion, and anatomical variations in the caliber and course of the internal carotid artery. Specific operative techniques for addressing each of these intraoperative challenges are discussed., Conclusions: Transsphenoidal surgery in patients with longstanding acromegaly frequently poses greater challenges than operations for other types of sellar lesions, yet these challenges may be safely and effectively overcome with the anticipation of specific issues and implementation of various intraoperative techniques.

The high mobility group As (HMGAs) belong to a family of nonhistone nuclear proteins that orchestrate the assembly of nucleoprotein complexes. Through a complex network of protein-DNA and protein-protein interaction, they play important roles in gene transcription, recombination, and chromatin structure. This protein family is involved, through different mechanisms, in both benign and malignant neoplasias. We have recently reported that transgenic mice carrying the Hmga1 or Hmga2 genes under transcriptional control of the cytomegalovirus promoter develop pituitary adenomas secreting prolactin and growth hormone. We have shown that the mechanism of the HMGA2-induced pituitary adenoma is based on the increased E2F1 activity. The expression profile of mouse normal pituitary glands and adenomas induced in HMGA transgenic mice revealed an increased expression of the ccnb2 gene, coding for the cyclin B2 protein, in the neoplastic tissues compared with the normal pituitary gland. Here, we show, by electrophoretic mobility shift assay and chromatin immunoprecipitation, a direct binding of HMGA proteins to the promoter of ccnb2 gene, whereas luciferase assays showed that HMGAs are able to up-regulate ccnb2 promoter activity. Finally, we report an increased CCNB2 expression in human pituitary adenomas of different histotypes that is directly correlated with HMGA1 and HMGA2 expression. Because cyclin B2 is involved in the regulation of the cell cycle, these results taken together indicate that HMGA-induced cyclin B2 overexpression gives an important contribution to experimental and human pituitary tumorigenesis.

The high-mobility group A (HMGA) family of proteins orchestrates the assembly of nucleoprotein structures playing important roles in gene transcription, recombination, and chromatin structure through a complex network of protein-DNA and protein-protein interactions. Recently, we have generated transgenic mice carrying wild type or truncated HMGA2 genes under the transcriptional control of the cytomegalovirus promoter. These mice developed pituitary adenomas secreting prolactin and GH mainly due to an increased E2F1 activity, directly consequent to the HMGA2 overexpression. To identify other genes involved in the process of pituitary tumorigenesis induced by the HMGA2 gene, in this study we have analyzed the gene expression profile of three HMGA2-pituitary adenomas in comparison with a pool of ten normal pituitary glands from control mice, using the Affymetrix MG MU11K oligonucleotide array representing approximately 13,000 unique genes. We have identified 82 transcripts that increased and 72 transcripts that decreased at least four-fold in all the mice pituitary adenomas analyzed compared with normal pituitary glands. Among these genes, we focused our attention on the Mia/Cd-rap gene, whose expression was essentially suppressed in all of the pituitary adenomas tested by the microarray. We demonstrated that the HMGA proteins directly bind to the promoter of the Mia/Cd-rap gene and are able to downregulate its expression. In order to understand a possible role of Mia/Cd-rap in pituitary cell growth, we performed a colony assay in GH3 and GH4 cells. Interestingly, Mia/Cd-rap expression inhibits their proliferation, suggesting a potential tumor suppressor role of Mia/Cd-rap in pituitary cells.

Pituitary tumors are a relatively common neoplasia whose pathogenesis is still largely unknown. Recent studies have revealed frequent activating mutations of the gene for B-RAF, an effector of Ras protein in the mitogen-activated protein kinase pathway, in several malignancies, including melanoma, thyroid, colorectal and ovarian cancer. However, analyses of B-RAF mutations in pituitary tumors have not been reported so far. Therefore, in the present study we have investigated the presence of the B-RAF mutations, by polymerase chain reaction (PCR) amplification of the hot spot exons 11 and 15, followed by direct sequencing, in 50 human pituitary adenomas, including 25 NFPA and 25 secreting adenomas (10 GH, 5 PRL, 6 LH and/or FSH, 4 GH/PRL). We found only one V600E mutation in a NFPA sample, suggesting that B-RAF mutations are a rare event in pituitary tumorigenesis.

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 microg/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 microg/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 role of somatostatin (SS) receptor subtype 1 (SSTR(1)) in mediating the inhibitory effect of SS on growth hormone (GH) secreting pituitary tumors has been recently demonstrated. In the present study, we evaluated the effect of the selective SSTR(1) agonist BIM-23745 on in vitro GH secretion in GH-secreting pituitary tumor cells, deriving from patients resistant or partially responsive to octreotide long-acting release (octreotide-LAR) or lanreotide therapy in vivo and expressing SSTR(1) mRNA. In addition, the inhibiting effect of BIM-23745 on the GH secretion was compared with that of octreotide. Our data demonstrate that (1) SSTR(1) receptor was present in 56.25% (9/16) of the GH-secreting adenomas examined; (2) in all GH-secreting pituitary tumors that expressed SSTR(1), BIM-23745 significantly inhibited GH secretion in vitro, and (3) when SSTR(1) subtype was present in tumors from patients resistant to octreotide-LAR or lanreotide therapy, BIM-23745 was able to inhibit the in vitro GH secretion. In conclusion, the results of the current study suggest that SS analogs selective for the SSTR(1) may represent a further useful approach for the treatment of acromegaly in patients resistant or partially responsive to octreotide-LAR or lanreotide treatment in vivo., (Copyright 2004 S. Karger AG, Basel)

The endoscopic endonasal transsphenoidal approach has been proposed in the past decade as a minimally invasive surgical technique for the removal of pituitary tumors. From January 1997 to November 1999, 100 consecutive patients with pituitary tumors underwent endoscopic endonasal surgery, according to Jho's technique. We employed 0 degrees, 30 degrees, 45 degrees, and 70 degrees rigid endoscopes, 18 - 30 cm in length, 4 mm in diameter with an outer sleeve for irrigation and secured to a holder. Among the 87 pituitary adenomas, tumor removal was total in 51, subtotal (> 80 %) in 20 and partial in 16 cases. Four craniopharyngiomas were totally removed and an intra-suprasellar arachnoid cyst was emptied; a biopsy was performed in the two patients with a clivus chordoma. The two cases of sphenoid sinusitis were cured by surgery, the three patients with spontaneous CSF rhinorrhea were successfully treated and the residual nasal meningocele was removed. The endoscopic endonasal transsphenoidal approach appeared to be less traumatic than the traditional microsurgical approach, was very effective, and was characterized by a reduced number of complications. However, the relatively small series together with the short follow-up do not allow us to draw definitive conclusions. The post-operative reduction in hospital stay (two days in 40 of 100), significantly reduced the cost of patient's management.

Object: To assess postoperative complications related to the surgical procedure, a retrospective analysis was conducted in a series of 146 consecutively treated patients who underwent an endoscopic endonasal transsphenoidal approach to the sellar region for resection of pituitary adenomas between January 1997 and July 2001., Methods: Complications were divided into groups (nasofacial, sphenoid sinus, sella turcica, supra or parasellar, and endocrine complications) according to the anatomical structures and the systems involved. Overall, a decreased incidence of complications has been observed, compared with large historical series of the traditional microsurgical transsphenoidal approach, likely because of the overview inside the anatomy facilitated by the endoscope, and the decreased surgical trauma., Conclusions: Transsphenoidal surgery, either microscopic or endoscopic, is a safe procedure in experienced hands, but serious complications still occur and must be reduced as much as possible. Additional improvement can be expected with greater experience and new technical developments. A coordinated team effort with other dedicated colleagues from different specialties is advised.

Severe hyponatremia (118 mmol/l) with natriuresis, consistent with cerebral salt wasting syndrome (CSWS), occurred 38 days after transsphenoidal surgery in a 59-year-old woman affected by a pituitary non-functioning macroadenoma. From the 35th day after surgery, she showed progressive polyuria, hypotension and hyponatremia associated with natriuresis, decreased plasma and increased urinary osmolality. The clinical examination revealed signs of dehydration and gradual decline in the level of consciousness. The anterior pituitary function was normal due to appropriate replacement of thyroid and adrenal axis. The patient was treated with saline administration until normal natremia and water balance were restored and neurological symptoms had completely disappeared. This case focuses on the unusually prolonged time of development of post-surgery hyponatremia, despite delayed symptomatic hyponatremia being reported to commonly occur 7 days after transsphenoidal surgery. Therefore, we would advise not to limit the periodic follow-up of the hydroelectrolytic balance to the first two weeks after surgery, but to prolong it until after discharge from hospital. In fact, an early diagnosis is of great importance to prevent permanent neurological damage or death. Since CSWS and syndrome of inappropriate secretion of ADH, the two disorders alternatively imputed to generate post-surgical hyponatremia, are characterized by different pathogenic mechanisms and require opposing therapeutic approaches, the occurrence of extracellular volume dilution or of increased sodium renal loss should be carefully investigated. The evidences in favor of CSWS, the possible mechanisms behind the syndrome and diagnosis and management of patients with post-transsphenoidal surgery CSWS are discussed.

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 +/- 5.6 microg/L; insulin-like growth factor I (IGF-I), 784.5 +/- 40.4 microg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery. Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12-24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (< or =2.5 microg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 +/- 0.6 vs. 2.2 +/- 0.6 microg/L) and IGF-I (323.1 +/- 34.9 vs. 275.5 +/- 33.0 microg/L), percent suppression of GH (92.7 +/- 2.0 vs. 85.9 +/- 3.3%) and IGF-I (57.4 +/- 4.9 vs. 61.5 +/- 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients. In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.

The endoscopic endonasal transsphenoidal approach to the sellar region for the removal of pituitary adenomas and of other neoplasms in the same area has proved its reliability and effectiveness for the very wide vision it offers, coupled with minimal surgical trauma. Indications and advantages of such a technique are reported, focused on the treatment of lesions of the sellar and parasellar environment in pediatric age-group patients, and based on a consecutive series of 100 patients, 3 of them adolescents, treated during the last 3 years.

Despite a good cure rate after surgery, the recurrence rate in pituitary adenomas is globally high. The decision making in such cases can be problematic for the nature of the lesion, for the anatomic structures involved, for the different pharmacological, surgical, radiotherapeutic and radiosurgical options nowadays available. In the perspective of an improvement and refinement of the surgical procedure an endoscopic endonasal transsphenoidal approach to the pituitary was recently adopted in the Neurosurgical Department of the University of Naples. Its minimal invasiveness and its wider and direct anatomic control of the operative field has allowed a faster, greater and safer potential of tumour excision, with respect of the sphenoid, sellar and parasellar structures. The authors have examined the advantages provided by this technique in 12 patients with recurrent pituitary adenomas and in 2 craniopharyngiomas already treated via a transnasal transsphenoidal approach (TTA), where the anatomy of surgical field had been distorted by the first operation or the radiation therapy. They conclude that the endoscopic transsphenoidal re-operation might be considered the procedure of choice in case of recurrences and its easiness in such conditions could favour its larger use, before other more aggressive therapeutic solutions.

Diaphragma sellae meningiomas are unusual tumours often not distinguished from pituitary macroadenomas. Preoperative differentiation is essential, because the trans-sphenoidal approach is used for surgical removal of adenomas, while meningiomas are approached via a craniotomy. We reviewed five patients in whom a diaphragma sellae meningioma was initially diagnosed as a nonsecreting pituitary macroadenoma. MRI criteria for differential diagnosis are discussed. The main findings considered are visibility of the pituitary gland, contrast enhancement, the centre of the lesion and sellar enlargement. These criteria, applied to a blind review, allow correct identification of the tumours.

The effect of surgery alone or followed by radiotherapy in recovering visual abnormalities, debulking tumor mass and restoring hormone impairments was evaluated in 84 patients with clinical nonfunctioning pituitary adenomas (NFPA) subjected to 1-10 yr follow-up. All patients underwent surgery via transsphenoidal (in 69) or transcranic-pterional approach (in 15). Radiotherapy was performed after surgery in 59 of 72 patients with incomplete tumor removal. The assessment of pituitary function was performed in all patients before and every 1-2 yr after surgery and/or radiotherapy. Radiological and ophthalmologic assessment was performed before and 3, 6 and 12 months after surgery, then yearly. At diagnosis, headache and visual disturbances occurred in 63 and 58 patients, respectively, while deficiency of GH, TSH, ACTH, FSH, LH and ADH was documented in 55, 7, 19 47 and 6 patients, respectively. After surgery, gonadal function recovered in 12 women, visual disturbances improved in 43 patients (15 regained normal vision), pituitary function improved in 8 of 62 patients, worsened in 34 patients. At MRI, complete tumor removal was documented in 12 of 84 patients. After surgery alone, tumor regrowth was observed in 7 patients between 3-7 yr. After radiotherapy, vision improved in 9, remained unchanged in 49 and worsened in 1 of 59 patients. After radiotherapy, tumor regrowth was documented in 9 patients between 2-12 yr and the prevalence of hypopituitarism raised from 28.8% to 92% after 1 and 10 yr. In conclusion, surgery alone is effective only in a minority of patients (14.3%) and radiotherapy causes hypopituitarism in rather the totality of patients after 10 yr. The prevalence of tumor regrowth was similar in irradiated ones (15%) and non irradiated patients (28%; chi(2), p = 0.4). Therefore, a careful radiological followup is suggested after surgery so that radiotherapy can be performed promptly on the basis of clinical data, tumor regrowth and/or invasiveness documented at histology.