Long-term outcomes of multidisciplinary treatment combining surgery and stereotactic radiotherapy with Novalis for craniopharyngioma.

Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.

Long-term outcomes after a transcranial microsurgical approach to craniopharyngiomas: a 20-year clinical follow-up study.

Craniopharyngioma (CP) is a mostly benign tumor that is nonetheless one of most formidable skull base lesions. CP tends to recur, and scarce clinical results are available regarding its long-term outcomes. From February 1996 to April 2002, craniopharyngiomas primarily resected by open surgery in a single-center and single-surgeon practice were screened. Medical information regarding patients' baseline, tumor parameters, endocrinological results, complications, and quality of life in those patients with a follow-up longer than 20 years were reviewed. Nineteen out of 187 patients who met the inclusion criteria were eligible, and 78.9% of the patients were admitted due to visual deficits. The transcranial approach was mostly applied for the first attempt of opening resection, with 94.7% gross total resection. The size of the tumor ranged from 25 to 45 mm with a mean maximal diameter of 34.7 mm. Although 7 out of 19 patients received an extra procedure, 6 patients (31.5%) regained fertility, with 3 women bearing a total of 5 children and 3 men fathering a total of 4 children, during the 21.4-year follow-up (range: 20.0-23.3 years). The mean Karnofsky Performance Status (KPS) score was 97.9 (range: 80-100) at the last follow-up, and the physical and mental 36-Item Short Form Health Survey (SF-36) scores were 88.0 and 80.5, respectively. The tumor sizes of the patients who regained fertility were not significantly different from those of the patients who remained infertile (t = 1.29, P > 0.2). The time interval from prior surgery to tumor resection for recurrent cases ranged from 0.3 to 17.4 years (mean, 7.3 years). There was no significant difference in the time until tumor recurrence in the patients who underwent a second surgery, a third surgery, or a fourth surgery. The satisfactory results in the present study revealed favorable long-term outcomes following the transcranial management of CPs, with acceptable endocrinological function and tumor-free survival. A decisive policy of open surgery with the objective of radical tumor removal remains a valid method for the primary treatment of CPs, aiming to avoid retreatment after tumor recurrence involving vital hypothalamic structures or hydrocephalus.

Statement in Support of Revising the Uniform Determination of Death Act and in Opposition to a Proposed Revision.

Discrepancies between the Uniform Determination of Death Act (UDDA) and the adult and pediatric diagnostic guidelines for brain death (BD) (the "Guidelines") have motivated proposals to revise the UDDA. A revision proposed by Lewis, Bonnie and Pope (the RUDDA), has received particular attention, the three novelties of which would be: (1) to specify the Guidelines as the legally recognized "medical standard," (2) to exclude hypothalamic function from the category of "brain function," and (3) to authorize physicians to conduct an apnea test without consent and even over a proxy's objection. One hundred seven experts in medicine, bioethics, philosophy, and law, spanning a wide variety of perspectives, have come together in agreement that while the UDDA needs revision, the RUDDA is not the way to do it. Specifically, (1) the Guidelines have a non-negligible risk of false-positive error, (2) hypothalamic function is more relevant to the organism as a whole than any brainstem reflex, and (3) the apnea test carries a risk of precipitating BD in a non-BD patient, provides no benefit to the patient, does not reliably accomplish its intended purpose, and is not even absolutely necessary for diagnosing BD according to the internal logic of the Guidelines; it should at the very least require informed consent, as do many procedures that are much more beneficial and less risky. Finally, objections to a neurologic criterion of death are not based only on religious belief or ignorance. People have a right to not have a concept of death that experts vigorously debate imposed upon them against their judgment and conscience; any revision of the UDDA should therefore contain an opt-out clause for those who accept only a circulatory-respiratory criterion.

Preservation of Hypothalamic Function with Endoscopic Endonasal Resection of Hypothalamus-Invaded Craniopharyngiomas.

OBJECTIVE: To analyze the preservation of hypothalamic function using the endoscopic endonasal approach (EEA) in a single-center clinical series of patients with hypothalamus-invaded craniopharyngioma (CP) and compare this series with reported cases by the open transcranial approach (TCA). METHODS: A retrospective review of hypothalamus-invaded CP surgical cases treated with EEA was performed. Hypothalamic damage was evaluated in terms of the body mass index (BMI), endocrine status, and quality of life before and after surgery. A review of the available literature reporting the use of EEA and TCA over the last decade was performed for comparison. RESULTS: In total, 63 cases amenable to EEA were investigated. The elevation in BMI was substantial and an increase in BMI greater than 9% was observed in 22 patients (34.92%). Most patients exhibited a BMI gain >9% within 3 months postoperatively. A total of 16 of the 19 patients who had normal anterior pituitary function preoperatively worsened after surgery. Of the 27 cases reporting preoperative partial hypopituitarism, 16 cases worsened postoperatively and 11 cases remained unchanged. All 9 cases with preoperative panhypopituitarism remained unchanged postoperatively. A total of 40 new cases developed diabetes insipidus, and 3 of the 10 patients with preoperative diabetes insipidus exhibited resolved at the latest follow-up. The quality of life showed no significant difference. CONCLUSIONS: EEA can achieve greater gross total resection than TCA when performed by an experienced surgeon. Combined with the reduced postoperative hypothalamic damage in our patients with only hypothalamus-invaded CP, especially the shortened time horizons of hypothalamic obesity development and reduced percentage of patients with obesity, the EEA technique should be a preferred alternative over TCA.

Pure endoscopic management of epileptogenic hypothalamic hamartomas.

Hypothalamic hamartomas (HH) are rare congenital malformations located in the region of the tuber cinereum and third ventricle. Their usual clinical presentation is characterized by gelastic/dacrystic seizures which often become pharmaco-resistant and progress to secondary focal/generalized intractable epilepsy causing mostly in children cognitive and behavioral problems (particularly in cases of progressive epileptic encephalopathy) and precocious puberty. Whereas gelastic seizures can be surgically controlled either by resection of the lesion or disconnection (tissue-destructive) procedures, aimed at functionally prevent the spreading of the epileptic burst; generalized seizures tend to respond better to HH excision rather than isolated neocortical resections, which generally fail to control them. Prospective analysis of 14 consecutive patients harboring HH treated in an 8-year period; 12 patients had unilateral and two bilateral HH. All patients were managed by pure endoscopic excision of the HH. The mean operative time was 48 min and mean hospital stay was 2 days; perioperative blood loss was negligible in all cases. Two patients showed a transient diabetes insipidus (DI); no transient or permanent postoperative neurological deficit or memory impairment was recorded. Complete HH excision was achieved in 10/14 patients. At a mean follow-up of 48 months, no wound infection, meningitis, postoperative hydrocephalus, and/or mortality were recorded in this series of patients. Eight patients became seizure free (Engel class I), 2 other experienced worthwhile improvement of disabling seizures (Engel class II); 2 patients were cured from gelastic attacks while still experiencing focal dyscognitive seizures; and 2, having bilateral HH (both undergoing unilateral HH excision), did not experience significant improvement and required later on a temporal lobectomy coupled to amygdalohyppocampectomy. Overall, the followings resulted to be predictive factors for better outcomes in terms of seizure control: (1) cases of unilateral, Delalande class B, HH, (2) shorter history of epilepsy. Endoscopic resection of HH proved, in our series, to be effective in achieving complete control or in reducing the frequency of seizures. Furthermore, this approach has confirmed its minimally invasive nature with a very low morbidity rate: of note, it allowed to better preserve short-term memory and hypothalamic function.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

OBJECTIVE: To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). STUDY DESIGN: Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. INTERVENTION(S): Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 µg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. RESULT(S): After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. CONCLUSION(S): Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.