Bilateral spheno-orbital meningiomas: surgical management, progression, and recurrence.

OBJECTIVE: Bilateral spheno-orbital meningiomas (bSOMs) are a rare entity among meningiomas. These tumors are benign and predominantly affect women. They represent 4% of spheno-orbital meningiomas (SOMs) and are poorly described in the literature. This study aimed to describe the characteristics, risk factors, evolution, and management of bSOMs. METHODS: Twenty patients with bSOMs were enrolled in a multicentric descriptive study including 15 neurosurgical departments. RESULTS: In this study, the authors found that bSOMs affected exclusively women, with a mean age of 50 years. Approximately 65% of patients were on progestin therapy. The mean follow-up in this series was 55 months. Clinically, visual symptoms were predominant: proptosis was present in 17 of 20 patients (85%; 7 unilateral, 10 bilateral), and a decrease in visual acuity was observed in 11 of 20 patients (55%; 6/10 to 9/10 in 6 patients, 3/10 to 5/10 in 1 patient, and < 3/10 in 4 patients). Contrary to unilateral SOMs, the authors identified that intracranial hypertension was a common presentation (25%) of bSOMs. Surgical management with gross-total resection was the gold standard treatment. Recurrences only occurred following subtotal resection in 36% to 60% of patients, with a median time of 50 to 54 months after surgery. Visual improvement or stability was observed in 75% of cases postoperatively. Progesterone receptor expression levels were 70% to 100% in 10 of 11 (91%) cases. CONCLUSIONS: Bilateral SOMs are usually found in female patients and are strongly associated with hormone replacement therapy. Early surgical management with gross-total resection is the most effective treatment in terms of recurrence and improves visual acuity. Given the slow progressive nature of bSOMs and their time to recurrence, which can be up to 10 years, long-term follow-up of patients is essential.

Are there Still any Benefits to Drainage for Anterior Cervical Arthrodesis/Arthroplasty by Cervicotomy?

STUDY DESIGN: A retrospective single-center study between January 2019 and 2023. OBJECTIVE: The role and contribution of drainage in the anterior approach to the cervical spine (cervicotomy) is much debated, motivated primarily by the prevention of retropharyngeal hematoma, so are there still any benefits to drainage? BACKGROUND: The anterior approach to the cervical spine is a widespread and common procedure performed in almost all spine surgery departments for the replacement of cervical intervertebral discs and medullar or radicular decompression. The primary endpoint was the occurrence of symptomatic postoperative cervical hematoma. METHODS: Four hundred thirty-one patients who had undergone cervical spine surgery by anterior cervicotomy for cervicarthrosis or cervical disc herniation (ACDF, ACDR) were consecutively included. Patients were separated into 2 groups: Group A, 140 patients (with postoperative drainage) and group B, 291 patients (without drainage). RESULTS: Mean follow-up was 2.8 months. The 2 groups were comparable on all criteria, but there was a predominance of arthroplasty (P<0.0001), use of anticoagulants/antiaggregants (P<0.0001) and a greater number of stages (P<0.0001) in group A. There were a total of 4/431 symptomatic postoperative hematomas (0.92%) in this study. Two hematomas occurred in group A (2/140, 1.4%) and two in group B (2/291, 0.68%) (P<0.0001). One patient in group A (0.71%) required surgical drainage for cavity hematoma revealed by marked dyspnea, swallowing and neurological disorders. One case of hematoma diagnosed by dysphonia and neurological deficit was reported in group B (0.34% (P<0.0001). CONCLUSIONS: Placement of a drain during anterior cervicotomy for (ACDF/ACDR) did not limit the occurrence of symptomatic postoperative hematoma.

Impact of metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fracture (pVCF) in neurological and survival prognosis.

BACKGROUND: Metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. METHODS: A French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. RESULTS: The median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7-12 [HR: 6.755, 95 % CI 2.40-19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185-0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107-0.456; p = 0.007] were independent risk factors for impaired neurological function. CONCLUSION: Contrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.

Multiple Myeloma Spinal Lesion Care: Management of a Primary Bone Malignancy Rather Than a Spinal Metastasis.

OBJECTIVE: Multiple myeloma (MM) is too often wrongly categorized as a spinal metastasis (SpM), although it is distinguishable from SpM in many aspects, such as its earlier natural history at the time of diagnosis, its increased overall survival (OS), and its response to therapeutic modalities. The characterization of these 2 different spine lesions remains a main challenge. METHODS: This study compares 2 consecutive prospective oncologic populations of patients with spine lesions: 361 patients treated for MM spine lesions and 660 patients treated for SpM between January 2014 and 2017. RESULTS: The mean time between the tumor/MM diagnosis and spine lesions was respectively 0.3 (standard deviation [SD] 4.1) and 35.1 months (SD 21.2) for the MM and SpM groups. The median OS for the MM group was 59.6 months (SD 6.0) versus 13.5 months (SD 1.3) for the SpM group (P < 0.0001). Regardless of Eastern Cooperative Oncology Group (ECOG) performance status, patients with MM always have a significantly better median OS than do patients with SpM: ECOG 0, 75.3 versus 38.7 months; ECOG 1, 74.3 versus 24.7 months; ECOG 2, 34.6 versus 8.1 months; ECOG 3, 13.5 versus 3.2 months and ECOG 4, 7.3 versus 1.3 months (P < 0.0001). The patients with MM had more diffuse spinal involvement (mean, 7.8 lesions; SD 4.7) than did patients with SpM (mean, 3.9; SD 3.5) (P < 0.0001). CONCLUSIONS: MM must be considered as a primary bone tumor, not as SpM. The strategic position of the spine in the natural course of cancer (i.e., nurturing cradle of birth for MM vs. systemic metastases spreading for SpM) explains the differences in OS and outcome.

Spinal lesions in multiple myeloma: Primary bone tumors with distinct prognostic factors.

PURPOSE: Although prognostic factors of spinal multiple myeloma (MM) seem to differ from those of other spine metastases (SpM), the data in the literature remains scarce. METHODS: A prospective population of 361 patients treated for spine MM lesions between January 2014 and 2017. RESULTS: OS for our series was 59.6 months (SD 6.0 months; CI 95%: 47.7-71.3). Cox multivariate proportional-hazards analysis showed that bone marrow transplant [HR: 0.390, 95% CI 0.264-0.577; p < 0.0001] and light-chain isotype [HR: 0.748, 95% CI 0.318-1.759; p = 0.005] were independent predictors of longer survival. In contrast, age >80 years [HR: 2.7, 95% CI 1.6-4.3; p < 0.0001], ISS III [HR: 2.510, 95% CI 2.01-3.124; p = 0.001], IgA isotype [HR: 1.475, 95% CI 1.031-2.11; p = 0.034] and IgD/M isotype [HR: 2.753, 95% CI 1.230-6.130; p = 0.013] were independent poor prognostic factors. However, ECOG (p = 0.486), spine surgery (p = 0.391), spine radiotherapy (p = 0.260), epidural involvement (p = 0.259), the number of vertebra lesions (p = 0.222), and synchronous/metachronous timeline (p = 0.412) were not significantly associated with improved OS. CONCLUSIONS: Spinal involvement in the context of MM does not influence OS. The main prognostic factors to consider before spinal surgery are the characteristics of the primary MM disease (ISS score, IgG isotype and systemic treatment).

Spine Metastasis: Patients With Poor Performance Status (ECOG) Could benefit From Palliative Surgical Care! A Prospective Cohort Study.

STUDY DESIGN: This study used a French prospective national multi-center database of patients with spine metastasis (SpM). OBJECTIVE: The main challenge was to clarify if SpM patients presenting poor ECOG-PS could benefit from a surgical intervention. BACKGROUND: Spine metastases (SpM) are debilitating lesions commonly found in the evolution of cancer. At present, patients with poor ECOG-PS do not benefit from surgical care. MATERIALS AND METHODS: Between 2014 and 2017, 176 SpM patients with poor initial ECOG-PS (3 or 4) were identified. RESULTS: The median overall survival of patients was 2.1 months (SD 0.2). Seventy-one patients (40.3%) underwent surgery: for 49 patients (27.8%) the intervention consisted of a simple decompression and for 22 patients (12.5%) the previous was associated with an osteosynthesis. Patients who underwent surgery demonstrated significantly longer median overall survival than those who did not: 3.5 months (SD 0.4) versus 1.6 (SD 0.2) ( P <0.0001). No significant differences between operated/nonoperated patients were noted concerning median age (66.4 vs. 64.2 y, P =0.897), the median number of SpM (4.1 vs. 4.2, P =0.374), ECOG-PS 4 ratio (41.6 vs. 39.3%, P =0.616), or for primary tumors ( P =0.103). Patients who underwent surgery statistically improved their neurological impairment according to the Frankel score: 5/11 (45.4%) from A to C, 5/17 (29.4%) from B to C or D, 6/11 (54.5%) from C to D and 2/4 (50%). Twelve patients (16.9%) presented a postoperative complication. CONCLUSION: Patients with poor ECOG-PS could benefit from surgery. Even though survival gain is small, it permits the preservation of their neurological function. By making ambulation possible, pain is decreased during the last months of their lives.

Cauda Equina Syndrome: Poor Recovery Prognosis Despite Early Treatment.

STUDY DESIGN: A prospective patient's database operated on a cauda equina syndrome (CES). OBJECTIVE: The aim of our study was to identify prognosis factors for favorable functional recovery after CES. SUMMARY OF BACKGROUND DATA: CES is a neurologic impairment of variable symptoms associating urinary, bowel, and sexual dysfunctions with or without motor or sensitive deficits caused by nerve root compression of the cauda equina. The definition of CES remains debated, as well as the prognosis factors for favorable functional recovery and the benefit of early surgery. METHODS: One hundred forty patients were included between January 2010 and 2019. Univariate and multivariate cox proportional hazard regression models were conducted. RESULTS: The patients were young with a median age of 46.8 years (range 18-86 yrs). At presentation, 60% were affected by a motor deficit, 42.8% a sensitive deficit, 70% urinary dysfunctions, and 44% bowel dysfunctions. The mean follow-up was 15.5 months. Bilateral motor deficit (P = 0.017) and an initial deficit severity of 0 to 2 (P = 0.001) represented prognosis factors of poor motor recovery. Initial anal incontinence (P = 0.007) was associated with poor bowel recovery. Only 32.8% of the patients went back to work. Initial motor deficit (P = 0.015), motor sequelae (P = 0.001), sphincter dysfunctions sequelae (P = 0.02), and long LOS (P = 0.02) were poor return-to-work prognosis factors. Time to surgery within an early timing < 24 or 48 hours or later did not represent a prognosis factor of recovery in CES. Incomplete versus complete CES did not show better recovery. CONCLUSION: CES remains a profound disabling syndrome with poor functional prognosis: in the long run, few patients go back to work. The main prognosis factors established in our series regarded the initial severity of deficits whether motor or sphincteral. Early or later surgical cauda equina decompression did not show to represent a prognosis factor for functional recovery.Level of Evidence: 4.

Peritumoral Edema/Tumor Volume Ratio: A Strong Survival Predictor for Posterior Fossa Metastases.

BACKGROUND: Twenty percent of all brain metastases (BM) occur in the posterior fossa (PF). Radiotherapy sometimes associated with surgical resection remains the therapeutic option, while Karnovsky performance status and graded prognostic assessment (GPA) are the best preoperative survival prognostic factors. OBJECTIVE: To explore the prognostic role of peritumoral brain edema in the PF, which has never been explored though its role in supratentorial BM has been debated. METHODS: A total of 120 patients diagnosed with PF metastasis who underwent surgical resection were included retrospectively in this analysis. Clinical data were retrieved from electronic patient medical files. The tumor volumes and their associated edema were calculated via manual delineation; subsequently the edema/tumor volume ratio was determined. RESULTS: In multivariate analysis with Cox multivariate proportional hazard model, the edema to tumor volumes ratio (hazard ratio [HR]: 1.727, 95% confidence interval [CI] 1.427-2.083; P < .0001) was identified as a new strong independent prognosis factor on overall survival (OS) whereas edema volume alone was not (P = .469). Moreover, BM complete resection (HR: 0.447, 95% CI 0.277-0.719; P < .001), low (0-1) World Health Organization status at diagnosis (HR: 2.109, 95% CI 1.481-3.015; P < .0001), high GPA class at diagnosis (HR: 1.77, 95% CI 0.9-2.9; P < .04), and postoperative brain irradiation (HR: 2.019, 95% CI 1.213-3.361; P < .007] were all confirmed as independent predictive factors for survival. CONCLUSION: The edema/tumor ratio appears to greatly influence OS in patients suffering from PF metastases unlike the extent of edema alone. This easily determined as well as strong prognostic factor could be used as an interesting tool in clinical practice to help the management of these patients.

Sex-Related Differences in Lactotroph Tumor Aggressiveness Are Associated With a Specific Gene-Expression Signature and Genome Instability.

Sex-related differences have been reported in various cancers, in particular men with lactotroph tumors have a worse prognosis than women. While the underlying mechanism of this sexual dimorphism remains unclear, it has been suggested that a lower estrogen receptor alpha expression may drive the sex differences observed in aggressive and malignant lactotroph tumors that are resistant to dopamine agonists. Based on this observation, we aimed to explore the molecular importance of the estrogen pathway through a detailed analysis of the transcriptomic profile of lactotroph tumors from 20 men and 10 women. We undertook gene expression analysis of the selected lactotroph tumors following their pathological grading using the five-tiered classification. Chromosomic alterations were further determined in 13 tumors. Functional analysis showed that there were differences between tumors from men and women in gene signatures associated with cell morphology, cell growth, cell proliferation, development, and cell movement. Hundred-forty genes showed an increased or decreased expression with a minimum 2-fold change. A large subset of those genes belonged to the estrogen receptor signaling pathway, therefore confirming the potent role of this pathway in lactotroph tumor sex-associated aggressiveness. Genes belonging to the X chromosome, such as CTAG2, FGF13, and VEGF-D, were identified as appealing candidates with a sex-linked dysregulation in lactotroph tumors. Through our comparative genomic hybridization analyses (CGH), chromosomic gain, in particular chromosome 19p, was found only in tumors from men, while deletion of chromosome 11 was sex-independent, as it was found in most (5/6) of the aggressive and malignant tumors. Comparison of transcriptomic and CGH analysis revealed four genes (CRB3, FAM138F, MATK, and STAP2) located on gained regions of chromosome 19 and upregulated in lactotroph tumors from men. MATK and STAP2 are both implicated in cell growth and are reported to be associated with the estrogen signaling pathway. Our work confirms the proposed involvement of the estrogen signaling pathway in favoring the increased aggressiveness of lactotroph tumors in men. More importantly, we highlight a number of ER-related candidate genes and further identify a series of target molecules with sex-specific expression that could contribute to the aggressive behavior of lactotroph tumors in men.

Therapeutic Failure in Trigeminal Neuralgia: from a Clarification of Trigeminal Nerve Somatotopy to a Targeted Partial Sensory Rhizotomy.

BACKGROUND: Trigeminal neuralgia (TN) is a severe unilateral facial pain involving 1 or more branches of the trigeminal nerve (CNV). Microvascular decompression is a standard curative treatment of pharmacoresistant classic TN. Alternative procedures used for secondary or idiopathic TN usually lead to a high rate of pain recurrence and sensitive deficits. Partial sensory rhizotomy (PSR) is one of these ablative procedures. However, the lack of anatomic knowledge about the somatotopy of CNV lead to variable results in pain relief and hypoesthesia. OBJECTIVE: To refine the somatotopy of CNV and bring new anatomic landmarks for PSR, studying a cohort of patients treated by a targeted PSR (TPSR). METHODS: Retrospective and consecutive cases of adult patients treated in our institution between March 2000 and June 2015 for pharmacoresistant TN without vascular compression were collected. Our surgical procedure was performed using a precision map of the somatotopy of CNV. We compared our results with other surgical and nonsurgical therapies. RESULTS: Twenty-two patients had undergone TPSR. Fourteen had an idiopathic TN without compression of the nerve root, 6 had a secondary TN caused by multiple sclerosis, and 2 had a trigeminal conflict by inoperable tumor. Complete pain relief was achieved in 86.4% of the patients. Postoperative hypoesthesia was partial and focalized (22.7%). TN recurrence rate at 5 years was 31.5% (standard deviation, 10.9%). CONCLUSIONS: We clarified the functional somatotopy of CNV in its juxtapontine portion. TPSR is an interesting alternative to other ablative procedures to treat pharmacoresistant TN without vascular compression.

Spinal metastases in multiple myeloma: A high-risk subgroup for ISS III patients.

BACKGROUND: Patients with multiple myeloma (MM) have an extremely heterogeneous prognosis. The International Staging System (ISS) is actually the most reliable staging system and chromosomal abnormalities were integrated in the Revised-ISS. We wanted to evaluate the prognostic value of spinal secondary localization in patients with MM and its impact on the ISS. METHODS: Epidemiological and biological data, as well as treatment protocols and secondary localization were analyzed for 650 consecutive patients diagnosed with MM from January 2006 to January 2017. RESULTS: The overall survival (OS) was dependent on the WHO performance status, ISS and Salmon and Durie stage at diagnosis. Furthermore, presence of spinal metastases at diagnosis was predictive of a worse outcome (p < 0.0001), while presence of peripheral bone metastases was not. Spinal metastases had a significant impact on OS for ISS III patients (p < 0.0001). Also, a history of bone marrow graft was associated with a better OS (p < 0.0001), while radiotherapy had no significant impact. The multivariate analysis confirmed that the spinal metastases at diagnosis determined a high-risk subgroup for ISS III patients with a very poor OS (p < 0.0001). CONCLUSIONS: Spinal metastases are a negative prognostic factor for patients with MM, especially for ISS III patients, and are associated with a shorter OS. Spinal metastasis should be systemically searched for and should be included in a modified staging system to better manage these patients.

The Socioeconomic Implications of Isolated Tibial and Femoral Fractures from Road Traffic Injuries in Uganda.

BACKGROUND: The purpose of this study was to determine the socioeconomic implications of isolated tibial and femoral fractures caused by road traffic injuries in Uganda. METHODS: This prospective longitudinal study included adult patients who were admitted to Uganda's national referral hospital with an isolated tibial or femoral fracture. The primary outcome was the time to recovery following injury. We assessed recovery using 4 domains: income, employment status, health-related quality of life (HRQoL) recovery, and school attendance of the patients' dependents. RESULTS: The majority of the study participants (83%) were employed, and they were the main income earner for their household (74.0%) at the time of injury, earning a mean annual income of 2,375 U.S. dollars (USD). All of the patients had been admitted with the intention of surgical treatment; however, because of resource constraints, only 56% received operative treatment. By 2 years postinjury, only 63% of the participants had returned to work, and 34% had returned to their previous income level. Overall, the mean monthly income was 62% less than preinjury earnings, and participants had accumulated 1,069 USD in debt since the injury; 41% of the participants had regained HRQoL scores near their baseline, and 62% of school-aged dependents, enrolled at the time of injury, were in school at 2 years postinjury. CONCLUSIONS: At 2 years postinjury, only 12% of our cohort of Ugandan patients who had sustained an isolated tibial or femoral fracture from a road traffic injury had recovered both economically and physically. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sphenoid Mucocele with Intracranial Extension: An Anatomic Perspective.

BACKGROUND: Isolated sphenoid mucoceles are rare, but because of their close proximity to important vasculonervous structures, local extension may result in serious consequences. CASE DESCRIPTION: A 47-year-old patient presented with headaches, meningismus, and a left homonymous lateral hemianopia. We report the atypical evolution of a posttraumatic sphenoid mucocele invading the sellar region and extending into the subarachnoid space with compression of the right optic tract, and we describe its surgical management. Further, with the aid of cadaveric specimens, we aim to analyze the precise pathway followed by the expanding collection from an anatomic perspective. CONCLUSIONS: Anatomic knowledge of the sellar and parasellar regions is the key to understand the process of how sphenoid mucoceles may extend intracranially. Early endoscopic drainage with a large sphenoidotomy allows favorable outcomes and prevents serious consequences.

Spheno-Orbital Meningiomas Surgery: Multicenter Management Study for Complex Extensive Tumors.

BACKGROUND: Spheno-orbital meningiomas (SOMs) are complex tumors involving the sphenoid wing, the orbit, and sometimes the cavernous sinus with bone hyperostosis and sheet-like dural involvement. Optimal removal, proptosis cure, and visual preservation remain a challenge. OBJECTIVE: To study the management of surgically treated SOMs. METHODS: The clinical records of 130 consecutive patients undergoing surgery for SOMs were retrospectively collected in a database during a 20-year period to analyze symptoms, surgical technique, clinical outcome, and follow-up. RESULTS: Among the 130 patients (mean age 51.2 ± 9.5 years), 91.5% were female. The most typical symptoms recorded were proptosis in 94.6%, visual impairment in 37.7%, and oculomotor paresis in 10.0%. Simpson grade I-II removal was achieved in 97 patients (74.6%). After 1 year, proptosis was improved in 60% of cases. A total of 44.9% of the patients with preoperative visual acuity impairment were improved. Periorbital excision was statistically linked to proptosis decreasing (P = 0.0001) and optic canal decompression was linked to visual stabilization (P = 0.03). Bone reconstruction prevented temporal muscle atrophy (P = 0.01) and unaesthetic results (P = 0.0001). Mean follow-up was 76.5 months (range 3-288 months), and the mean time for recurrence was 54.2 months. CONCLUSIONS: A single-stage optimal surgery with bone reconstruction appears to be the best first-line treatment, on a case-by-case analysis. Optic canal decompression and periorbital excision have to be performed in case of visual disturbance and proptosis. SOMs require a long-term follow-up because of a delayed high rate of recurrence.

Natural course and prognosis of anaplastic gangliogliomas: a multicenter retrospective study of 43 cases from the French Brain Tumor Database.

Background: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. Methods: Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively. Results: Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis. Conclusions: We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival.

Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry.

CONTEXT: Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. DESIGN: The French Registry contains data on acromegaly epidemiology, management and comorbidities recorded over more than three decades, retrospectively until 1999 and prospectively from 1999 to 2012. RESULTS: Data could be analyzed for 999 of the 1034 patients included in the registry (46% males). Disease control, defined as IGF-I normalization (adjusted for age and sex), was achieved in 75% of patients at the last follow-up visit. Half the patients with uncontrolled disease had IGF-I levels below 1.5 times the upper limit of normal (ULN). The proportion of patients with surgically cured disease did not change markedly over time, whereas the proportion of patients with uncontrolled disease fell and the proportion of patients with medically controlled disease rose. Cardiovascular, metabolic, respiratory and rheumatologic comorbidities and their outcomes were recorded for most patients, and no noteworthy overall deterioration was noted over time. Cancer occurred in 10% of patients, for a standardized incidence ratio of 1.34 (95% CI: 0.94-1.87) in men and 1.24 (0.77-1.73) in women. Forty-one patients died during follow-up, for a standardized mortality ratio of 1.05 (0.70-1.42). Most deaths were due to cancer. CONCLUSIONS: The majority of patients with acromegaly now have successful disease control thanks to the multistep management. The incidence of comorbidities following diagnosis of acromegaly is very low. Life expectancy is now close to that of the general population, probably owing to better management of the GH/IGF-I excess and comorbidities.

Expression of estrogen receptor alpha is associated with prolactin pituitary tumor prognosis and supports the sex-related difference in tumor growth.

CONTEXT: A sex difference in the progression of prolactin (PRL) tumors has been disputed for years. OBJECTIVE: To compare tumor characteristics and postoperative clinical course between men and women, and correlate data with estrogen receptor alpha (ERα (ESR1)) expression status. DESIGN, PATIENTS, AND METHODS: Eighty-nine patients (59 women and 30 men) operated on for a prolactinoma and followed for at least 5 years were selected. Tumors were classified into five grades according to their size, invasion, and proliferation characteristics. The ERα expression was detected by immunohistochemistry and a score (0-12) calculated as the product of the percentage of positive nuclei and the staining intensity. RESULTS: We found a significant preponderance of high-grade tumors among men and a lower surgical cure rate in men (23%) than in women (71%). Patients resistant to medical treatment were mainly men (7/8), six of whom showed tumor progression despite postoperative medical treatment, which led to multiple therapies and eventually death in three. The median score for ERα expression was 1 in men (range, 0-8) and 8 in women (range, 0-12) (P<0.0001). The expression of ERα was inversely correlated with tumor size (r=-0.59; P<0.0001) and proliferative activity. All dopamine agonist-resistant tumors and all grade 2b (invasive and proliferative) tumors (from ten men and four women) were characterized by low ERα expression. CONCLUSIONS: PRL tumors in men are characterized by lower ERα expression, which is related to higher tumor grades, resistance to treatment, and an overall worse prognosis.

A deletion causing NF2 exon 9 skipping is associated with familial autosomal dominant intramedullary ependymoma.

BACKGROUND: Intramedullary ependymomas are rare and benign tumors in the adult. Little is known about their physiopathology, but the implication of the NF2 gene is suspected because of their presence in a third of patients with type 2 neurofibromatosis (NF2), a disorder caused by mutation of the NF2 gene. METHODS: We conducted a clinical and genetic study of a family in which 5 of 9 members suffered from intramedullary ependymoma. Karyotyping and CGH array analysis were performed on DNA from peripheral blood lymphocytes from affected participants. The NF2 gene sequences were then determined in DNA from 3 nonaffected and all 5 affected members of the family. RESULTS: Karyotype and CGH array findings were normal. Sequencing of NF2 revealed a heterozygous deletion, c.811-39_841del69bp, at the intron 8/exon 9 junction, in all affected members that was absent from all nonaffected members. RT-PCR analysis and sequencing revealed a novel NF2 transcript characterized by a skipping of exon 9 (75 bp). This deletion is predicted to result in a 25-amino acid deletion in the N-terminal FERM domain of neurofibromin 2. Modeling of this mutant domain suggests possible disorganization of the subdomain C. CONCLUSION: We report the first family with an NF2 mutation associated with intramedullary ependymomas without other features of NF2 syndrome. This mutation, which has not been described previously, may particularly affect the function of neurofibromin 2 in ependymocytes leading to the development of intramedullary WHO grade II ependymomas. We propose that sporadic intramedullary ependymomas should also be analyzed for this region of NF2 gene.

Expression of somatostatin receptors, SSTR2A and SSTR5, in 108 endocrine pituitary tumors using immunohistochemical detection with new specific monoclonal antibodies.

Medical treatment of endocrine pituitary tumors with somatostatin analogs depends on tumor type and somatostatin receptor (SSTR) expression. Immunohistochemical detection of these receptors using polyclonal antibodies has given conflicting results. We studied the expression of SSTR(2A) and SSTR(5) with new procedures in 108 pituitary tumors. Using 2 new, specific monoclonal antibodies (clone UMB-1 and UMB-4), 2 fixatives (Bouin-Hollande and zinc-formalin) and 2 technical procedures (manual and automated), SSTR(2A) and SSTR(5) expression was studied in 60 GH (growth hormone), 15 ACTH (adrenocorticotropic hormone), 23 FSH/LH (follicle-stimulating hormone/luteinizing hormone), 7 PRL (prolactin), and 3 TSH (thyroid-stimulating hormone) tumors. Only membrane staining was taken into account, and the SSTR expression was considered positive when more than 5% of the cells were immunoreactive. GH tumors were classified as GH or GH/PRL, densely or sparsely granulated, and into 3 groups according to the percentage of SSTR-immunoreactive cells (group 1: <25%; group 2: 25%-75%; group 3: >75%). Almost all GH tumors expressed SSTR(2A) (93%) and SSTR(5) (83%) at high levels (group 3: >75%) in 52% and 37%, respectively. SSTR(2A) expression was significantly higher in densely than in sparsely granulated tumors. Moreover, SSTR(2A) was also expressed in the 3 TSH tumors and weakly expressed in 26% of the FSH/LH tumors, although not in ACTH or PRL tumors. SSTR(5) expression was noted in 2 of the 3 TSH tumors, in only 20% of ACTH tumors, and was absent from FSH/LH and PRL tumors. The immunohistochemical detection of SSTR is a reproducible and specific method that could help direct the choice of postoperative medical treatment.