Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis.

CONTEXT: The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. OBJECTIVE: To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. METHODS: Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. RESULTS: A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. CONCLUSIONS: In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.

The Pathophysiology of Early Hypotension Following Epinephrine-containing Local Anesthetic Infiltration of the Nasal Mucosa in Patients Undergoing Endoscopic Transsphenoidal Hypophysectomy: A Prospective, Observational Study.

In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of ß2-adrenoceptors producing vasodilation.

Indication and limitations of endoscopic extended transsphenoidal surgery for craniopharyngioma.

The transsphenoidal approach has been utilized in intrasellar craniopharyngioma surgeries. However, the advent of endoscopic extended transsphenoidal approach (EETSA) has expanded its indication to suprasellar craniopharyngiomas. We compared the indication and limitations of EETSA to those of unilateral basal interhemispheric approach (UBIHA), which presents similar indications for surgery. We analyzed 30 patients with tumors located below the foramen of Monro and the lateral boundary extending slightly beyond the internal carotid artery (UBIHA: N = 18; EETSA: N = 12). Postoperative magnetic resonance imaging (MRI) revealed gross total resection in 10 patients in the EETSA group (83.3%) and 12 in the UBIHA group (66.7%). Postoperative MRI in the EETSA group revealed residual tumor at the cavernous sinus in one patient, at the prepontine in one; in the UBIHA group, residual tumors were located in the retrochiasmatic area in two patients, infundibulum-hypothalamus in one, on the stalk in one, and in the intrasellar region in two. No intergroup differences were observed in the preservation of pituitary function and postoperative improvement of visual function. The extent of resection was better with EETSA than with UBIHA. EETSA is considered the first-line therapy because the distance between the optic chiasm and the superior border of the pituitary is large; the lateral extension does not go beyond the internal carotid artery; and the tumor does not extend inferiorly beyond the posterior clinoid process. However, in patients showing poorly developed sphenoid sinuses or pituitary stalks anterior to the tumor, surgery is difficult regardless of the selection criteria.

Childhood craniopharyngioma - changes of treatment strategies in the trials KRANIOPHARYNGEOM 2000/2007.

BACKGROUND: Prognosis in childhood cranio-pharyngioma, is frequently impaired due to sequelae. Radical surgery was the treatment of choice for decades. Even at experienced facilities radical surgery can result in hypothalamic disorders such as severe obesity. OBJECTIVE: We analyzed, whether treatment strategies for childhood craniopharyngioma patients recruited in GPOH studies have changed during the last 12 years. MATERIALS AND METHODS: We compared the grade of pre-surgical hypothalamic involvement, treatment, degree of resection and grade of surgical hypothalamic lesions between patients recruited in KRANIOPHARYNGEOM 2000 (n=120; 2001-2007) and KRANIOPHARYNGEOM 2007 (n=106; 2007-2012). RESULTS: The grade of initial hypothalamic involvement was similar in patients treated 2001-2007 and 2007-2012. The realized treatment was more radical (p=0.01) in patients recruited 2001-2007 (38%) when compared with patients treated 2007-2012 (18%). In patients with pre-surgical involvement of anterior/posterior hypothalamic areas, the rate of hypothalamus-sparing operations resulting in no (further) hypothalamic lesions was higher (p=0.005) in patients treated 2007-2012 (35%) in comparison with the 2001-2007 cohort (13%). Event-free-survival rates were similar in both cohorts. CONCLUSIONS: A trend towards less radical surgical approaches is observed, which was accompanied by a reduced rate of severe hypothalamic lesions. Radical surgery is not an appropriate treatment strategy in patients with hypothalamic involvement. Despite previous recommendations to centralize treatment at specialized centers, a trend towards further decentralization was seen.

Magnetic resonance imaging-graded hypothalamic compression in surgically treated adult craniopharyngiomas determining postoperative obesity.

OBJECT: Obesity as a consequence of management of pediatric craniopharyngioma is a well-described phenomenon related to the degree of hypothalamic involvement. However, weight change and obesity have not been analyzed in adult patients. Therefore, the purpose of this study was 1) to evaluate the pattern of postoperative weight gain related to preoperative body mass index (BMI), 2) determine if postoperative weight gain is an issue in adult patients, and 3) develop an objective MR imaging grading system to predict risk of postoperative weight gain and obesity in adults treated for craniopharyngioma. METHODS: The authors retrospectively screened 296 patients with known craniopharyngioma for the following inclusion criteria: pathologically confirmed craniopharyngioma, index surgery at the authors' institution, and operative weight and height recorded with at least 3 months of follow-up including body weight measurement. Patients aged 18 years or younger were excluded, yielding 28 cases for analysis. Cases of craniopharyngiomas were compared with age- and sex-matched controls (pituitary adenoma patients) to evaluate the pattern and significance of perioperative weight changes. RESULTS: Mean age was 46 +/- 17 years at surgery, and 64% of the patients were male. Complete resection was achieved in 71% of cases. There was no correlation of preoperative BMI and postoperative weight gain testing in a linear model. Sixty-one percent and 46% of patients had postoperative weight gains greater than 4 and 9%, respectively. Comparing craniopharyngioma patients (cases) to age- and sex-matched controls, the preoperative BMIs were similar (p = 0.93) between cases (mean 28.9 [95% CI 30.9-26.9]) and controls (mean 29.3 [95% CI 31.9-26.7]). However, there was a trend to a greater mean postoperative weight change (percentage) in cases (10.1%) than in controls (5.6%) (p = 0.24). Hypothalamic T2 signal change and irregular contrast enhancement correlated and predicted higher-grade hypothalamic involvement. Furthermore, they can be used to objectively grade hypothalamic involvement as the authors propose. Progressive hypothalamic involvement correlated with larger postoperative weight gains (p = 0.022); however, hypothalamic involvement did not correlate with preoperative BMI (p = 0.5). CONCLUSIONS: Postoperative weight gain in adult patients undergoing surgery for craniopharyngioma is a significant problem and correlates with hypothalamic involvement, as it does in pediatric patients. Finally, objective MR imaging criteria can be used to predict risk of postoperative weight gain and aid in grading of hypothalamic involvement.

The response of magnocellular neurons of the hypothalamo-neurohyphyseal system to hypophysectomy, nitric oxide synthase expression as well as survival and regeneration in developing vs. adult rats.

This study examined the age-related changes in nitric oxide synthase immunoreactivity (NOS-IR), survival and regeneration of magnocellular neurons in the hypothalamo-neurohypophyseal system (HNS) in rats following hypophysectomy. In adult animal, hypophysectomy induced a significant increase in NOS-IR in the supraoptic (SON), paraventricular nuclei (PVN) and median eminence (ME) by 3 days post-lesion. NOS sustained an increased level until 2 weeks after hypophysectomy and then returned to normal control level. In contrast, at postnatal day 7 (PN7), no obvious increase in NOS-IR was observed in the SON, PVN and ME following the injury compared with age-matched controls. At PN14, the same injury induced an increase in NOS-IR in SON, PVN and ME but the increase was more transient with peak NOS-IR at 3 days and returning to the corresponding control level at 1 week after hypophysectomy. In contrast to a striking age-dependent alteration in NOS-IR in the SON and PVN, hypophysectomy induced substantial degeneration of arginine vasopressin (AVP) and oxytocin (OT) neurons in the SON and PVN in both immature and adult rats and there was no obvious difference in neuronal survival after the same injury among these three groups of different ages by quantitative analysis. Following hypophysectomy, a large number of fibers were observed in the contact zone of the median eminence and the adjacent lumen of the third cerebral ventricle (V3) in adult rats, whereas few fibers could be found in the lumen of the V3 in the immature rats after the same injury. Relationships between NOS induction and magnocellular neuronal survival and regeneration were discussed.

Gamma knife surgery of the pituitary: new treatment for thalamic pain syndrome.

OBJECT: Although reports in the literature indicate that thalamic pain syndrome can be controlled with chemical hypophysectomy, this procedure is associated with transient diabetes insipidus. It was considered reasonable to attempt gamma knife surgery (GKS) to the pituitary gland to control thalamic pain. METHODS: Inclusion criteria in this study were poststroke thalamic pain, failure of all other treatments, intolerance to general anesthetic, and the main complaint of pain and not numbness. Seventeen patients met these criteria and were treated with GKS to the pituitary. The target was the pituitary gland together with the border between the pituitary stalk and the gland. The maximum dose was 140 to 180 Gy. All patients were followed for more than 3 months. CONCLUSIONS: An initial significant pain reduction was observed in 13 (76.5%) of 17 patients. Some patients experienced pain reduction within 48 hours of treatment. Persistent pain relief for more than 1 year was observed in five (38.5%) of 13 patients. Rapid recurrence of pain in fewer than 3 months was observed in four (30.8%) of 13 patients. The only complication was transient diabetes insipidus in one patient. It would seem that GKS of the pituitary might have a role to play in thalamic pain arising after a stroke.

[Endonasal transsphenoidal surgery under local anesthesia for elderly patient with pituitary tumor: case report].

We present a surgical case under local anesthesia of an 88-year-old woman suffering from visual disturbance caused by pituitary adenoma. Magnetic resonance (MR) imaging showed a large pituitary tumor with suprasellar extension compressing the chiasmatic nerve. Neither she nor her family would agree to surgical therapy. However, when we proposed surgery under local anesthesia, they accepted it. Partial removal of the tumor via the endonasal transsphenoidal approach was carried out, uneventfully. The nasal surface was infiltrated with 4%-Xylocaine prior to the ordinary xylocaine injection to the nasal mucosa. The patient did not complain of any pain associated with the surgical procedure, including saline injection to the subarachnoid space through spinal drainage. The postoperative course was fine except for the temporarily appearance of diabetes insipidus. Postoperative MR imaging showed complete relief of compression to the chiasmatic nerve. Her visual field was improved dramatically. Endonasal transsphenoidal surgery under local anesthesia is thought to be one of the most useful methods of choice, especially in cases of elderly patient with pituitary tumor.

[Endoscopic transnasal sphenoidal approach in hypophysectomy].

OBJECTIVE: To report the anesthetization and surgical method of transnasal-sphenoidal endoscopic approach in hypophysectomy. METHODS: Forty-two cases with pituitary tumor underwent tranasal-sphenoidal endoscopic surgery and 37 out of 42 accepted local anesthesia and sedation. RESULTS: No complications had occurred, the operations went successfully with less blood loss. Postoperative endoscopic follow-up period was performed at 6 to 35 months. The symptoms were improved in all patients. CONCLUSION: Our results show that transnasal-sphenoidal endoscopic approach under local anesthesia in the treatment of pituitary tumor seems to be a safe simple and valuable way.