scholarly journals Pegvisomant and Pasireotide LAR as second line therapy in acromegaly: clinical effectiveness and predictors of response

2021 ◽  
Vol 184 (2) ◽  
pp. 217-229
Author(s):  
Sabrina Chiloiro ◽  
Antonella Giampietro ◽  
Federica Mirra ◽  
Federico Donfrancesco ◽  
Tommaso Tartaglione ◽  
...  
Keyword(s):  
First Generation ◽  
Third Ventricle ◽  
Free Time ◽  
Second Line ◽  
Tumor Extension ◽  
The Third ◽  
Clinical Biomarkers ◽  
Predictors Of Response ◽  
Igf I ◽  
Pre Treatment

Background The treatment of acromegaly resistant to first-generation somatostatin receptor ligands (SRLs) is often difficult. Pegvisomant and Pasireotide LAR are mostly used in these subset of patients, as second line therapies. Choice of the type of second line therapies is difficult, since predictors of response are still unclear, impairing personalized therapy. We aimed to investigate predictors of response to Pegvisomant and Pasireotide LAR. Methods Seventy-four acromegaly patients entered this observational, cross-sectional and retrospective study if (i) resistant to high dose first-generation SRLs and (ii) treated with Pegvisomant and Pasireotide LAR for at least 12 consecutive months. Patients treated with radiotherapy in the previous 10 years were excluded. Results Fourty-one patients were treated with Pegvisomant and 33 with Pasireotide LAR. At the end of the study, acromegaly was controlled in 35 patients treated with Pegvisomant (85.4%) and in 23 treated with Pasireotide LAR (69.7%). In this cohort, a poor Pegvisomant response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P = 0.004, HR: 1.6, 95%CI: 1.2–4.6), with a Ki67-Li >4% (P = 0.004, HR: 3.49, 95%CI: 1.4–4.0) and with pre-treatment IGF-I >3.3×ULN (P=0.03, HR: 1.3, 95%CI: 1.1–6.0). A poor Pasireotide LAR response and a shorter progression free time were observed in cases with tumor extension to the third ventricle (P=0.025, HR: 1.6 95%CI: 1.4–3.4), pre-treatment IGF-I >2.3×ULN (P=0.049, HR: 2.4, 95%CI: 1.4–8.0), absent/low SST5 membranous expression (P=0.023 HR: 4.56 95%CI: 1.3–6.4) and in patients carried the d3-delated GHR isoform (P=0.005, HR: 11.37, 95%CI: 1.3–20.0). Conclusion Molecular and clinical biomarkers can be useful in predicting the responsiveness to Pegvisomant and Pasireotide LAR.

Endoscopic Surgery for Tumors in and around the Third Ventricle

2020 ◽  
Author(s):  
Kenichi Oyama ◽  
Toshio Hirohata ◽  
Keisuke Onoda ◽  
Shigeyuki Tahara ◽  
Akira Teramoto ◽  
...  
Keyword(s):  
Endoscopic Surgery ◽  
Third Ventricle ◽  
The Third

Clinical features and operative technique of transinfundibular craniopharyngioma

2020 ◽  
Vol 133 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Bin Tang ◽  
ShenHao Xie ◽  
GuanLin Huang ◽  
ZhiGang Wang ◽  
Le Yang ◽  
...  
Keyword(s):  
Clinical Features ◽  
Operative Technique ◽  
Third Ventricle ◽  
Radical Resection ◽  
The Third ◽  
Expanded Endonasal Approach ◽  
Sequencing Studies ◽  
Characteristic Features ◽  
Mri Study ◽  
Adamantinomatous Craniopharyngioma

OBJECTIVETransinfundibular craniopharyngioma (TC) is one of the 4 subtypes of suprasellar craniopharyngioma. In this study, the authors analyzed the clinical features of and operative technique for TC.METHODSA total of 95 consecutive cases of suprasellar craniopharyngioma that had been resected via the endoscopic expanded endonasal approach were retrospectively reviewed. Patients were divided into 2 groups: 34 in the TC group and 61 in the nontransinfundibular craniopharyngioma (NC) group. Clinical and radiographic features, intraoperative findings, histopathological and genetic findings, and surgical outcomes were analyzed and compared between groups.RESULTSCompared with NC, TC was mostly seen in adult patients (97.1%); it was rare in children (2.9%). Clinical presentations tended toward headache, hydrocephalus, and diabetes insipidus. The relatively smaller volume, midline location (consistent with the stalk position), unidentifiable stalk, no shift of the third ventricle, and greater likelihood to involve the third ventricle and cause hydrocephalus were the characteristic features of TC in the preoperative MRI study. According to the degree of vertical extension of the tumor, the 34 TCs could be classified into 3 subtypes: type 1, entity was limited to stalk (n = 2, 5.9%); type 2, tumor extended up to the third ventricle (type 2a) or down to the subdiaphragmatic cavity (type 2b) (n = 23, 67.6%); and type 3, tumor extended in both directions (n = 9, 26.5%). For TC resection, the chiasm–pituitary corridor, lamina terminalis corridor, and pituitary corridor could be used separately or jointly. Most of the TCs originated from the infundibulum–tuber cinereum, grew within and along the long axis of the infundibulum, and the pituitary stalk was not usually preserved in TCs (20.6%), whereas the rate of preservation was higher (80.3%) in NCs. Bilateral hypothalamic injury was found in nearly all TCs if radical resection was performed, whereas the relationship between NCs and hypothalamus was either compression (32.8%) or unilateral invasion (67.2%). Meanwhile, the postoperative endocrine and neuropsychological function outcomes in patients with TC were worse than in patients with NC. The genetic analysis with whole-exome sequencing studies showed no differential mutations of CTNNB1 (β-catenin) and BRAF (V600E) between TC and NC subtypes, but there was a difference between adamantinomatous craniopharyngioma and papillary craniopharyngioma.CONCLUSIONSTC is a special subtype of suprasellar craniopharyngioma, which is remarkably different from NC. Identification of this type of tumor preoperatively is essential for the planning of appropriate surgical approach and degree of excision.

Law and Economics

2020 ◽  
pp. 84-102
Author(s):  
Daniel B. Kelly
Keyword(s):  
Economic Analysis ◽  
First Generation ◽  
Law And Economics ◽  
Private Law ◽  
Foreseeable Future ◽  
Business Associations ◽  
The Third ◽  
Starting Point ◽  
The Law ◽  
The Impact

This chapter analyzes how law and economics influences private law and how (new) private law is influencing law and economics. It focuses on three generation or “waves” within law and economics and how they approach private law. In the first generation, many scholars took the law as a starting point and attempted to use economic insights to explain, justify, or reform legal doctrines, institutions, and structures. In the second generation, the “law” at times became secondary, with more focus on theory and less focus on doctrines, institutions, and structures. But this generation also relied increasingly on empirical analysis. In the third generation, which includes scholars in the New Private Law (NPL), there has been a resurgence of interest in the law and legal institutions. To be sure, NPL scholars analyze the law using various approaches, with some more and some less predisposed to economic analysis. However, economic analysis will continue to be a major force on private law, including the New Private Law, for the foreseeable future. The chapter considers three foundational private law areas: property, contracts, and torts. For each area, it discusses the major ideas that economic analysis has contributed to private law, and surveys contributions of the NPL. The chapter also looks at the impact of law and economics on advanced private law areas, such as business associations, trusts and estates, and intellectual property.

scholarly journals Development of a Prognostic Model to Predict Mortality after Traumatic Brain Injury in Intensive Care Setting in a Developing Country

2021 ◽  
Vol 12 (02) ◽  
pp. 368-375
Author(s):  
Mini Jayan ◽  
Dhaval Shukla ◽  
Bhagavatula Indira Devi ◽  
Dhananjaya I. Bhat ◽  
Subhas K. Konar
Keyword(s):  
Traumatic Brain Injury ◽  
Intensive Care ◽  
Brain Injury ◽  
Hospital Mortality ◽  
Prognostic Model ◽  
Third Ventricle ◽  
The Third ◽  
Scan Data ◽  
Gcs Score ◽  
Basal Cisterns

Abstract Objectives We aimed to develop a prognostic model for the prediction of in-hospital mortality in patients with traumatic brain injury (TBI) admitted to the neurosurgery intensive care unit (ICU) of our institute. Materials and Methods The clinical and computed tomography scan data of consecutive patients admitted after a diagnosis TBI in ICU were reviewed. Construction of the model was done by using all the variables of Corticosteroid Randomization after Significant Head Injury and International Mission on Prognosis and Analysis of Clinical Trials in TBI models. The endpoint was in-hospital mortality. Results A total of 243 patients with TBI were admitted to ICU during the study period. The in-hospital mortality was 15.3%. On multivariate analysis, the Glasgow coma scale (GCS) at admission, hypoxia, hypotension, and obliteration of the third ventricle/basal cisterns were significantly associated with mortality. Patients with hypoxia had eight times, with hypotensions 22 times, and with obliteration of the third ventricle/basal cisterns three times more chance of death. The TBI score was developed as a sum of individual points assigned as follows: GCS score 3 to 4 (+2 points), 5 to 12 (+1), hypoxia (+1), hypotension (+1), and obliteration third ventricle/basal cistern (+1). The mortality was 0% for a score of “0” and 85% for a score of “4.” Conclusion The outcome of patients treated in ICU was based on common admission variables. A simple clinical grading score allows risk stratification of patients with TBI admitted in ICU.

scholarly journals Survival of glioblastoma in relation to tumor location: a statistical tumor atlas of a population-based cohort

2021 ◽  
Author(s):  
Even Hovig Fyllingen ◽  
Lars Eirik Bø ◽  
Ingerid Reinertsen ◽  
Asgeir Store Jakola ◽  
Lisa Millgård Sagberg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Elderly Patients ◽  
Temporal Lobe ◽  
Third Ventricle ◽  
Tumor Location ◽  
Population Based ◽  
Independent Effect ◽  
Precentral Gyrus ◽  
The Third

Abstract Purpose Previous studies on the effect of tumor location on overall survival in glioblastoma have found conflicting results. Based on statistical maps, we sought to explore the effect of tumor location on overall survival in a population-based cohort of patients with glioblastoma and IDH wild-type astrocytoma WHO grade II–III with radiological necrosis. Methods Patients were divided into three groups based on overall survival: < 6 months, 6–24 months, and > 24 months. Statistical maps exploring differences in tumor location between these three groups were calculated from pre-treatment magnetic resonance imaging scans. Based on the results, multivariable Cox regression analyses were performed to explore the possible independent effect of centrally located tumors compared to known prognostic factors by use of distance from center of the third ventricle to contrast-enhancing tumor border in centimeters as a continuous variable. Results A total of 215 patients were included in the statistical maps. Central tumor location (corpus callosum, basal ganglia) was associated with overall survival < 6 months. There was also a reduced overall survival in patients with tumors in the left temporal lobe pole. Tumors in the dorsomedial right temporal lobe and the white matter region involving the left anterior paracentral gyrus/dorsal supplementary motor area/medial precentral gyrus were associated with overall survival > 24 months. Increased distance from center of the third ventricle to contrast-enhancing tumor border was a positive prognostic factor for survival in elderly patients, but less so in younger patients. Conclusions Central tumor location was associated with worse prognosis. Distance from center of the third ventricle to contrast-enhancing tumor border may be a pragmatic prognostic factor in elderly patients.

Neurosurgical anatomy of the floor of the third ventricle and related vascular structures

2021 ◽  
Author(s):  
João Fernandes-Silva ◽  
Susana M. Silva ◽  
Hélio Alves ◽  
José P. Andrade ◽  
Mavilde Arantes
Keyword(s):  
Third Ventricle ◽  
The Third ◽  
Vascular Structures
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