Impact of frailty on short-term outcomes in patients undergoing transsphenoidal pituitary surgery.

OBJECTIVE: Frailty, a state of decreased physiological reserve, has been shown to significantly impact outcomes of surgery. The authors sought to examine the impact of frailty on the short-term outcomes of patients undergoing transsphenoidal pituitary surgery. METHODS: Weighted data from the 2000-2014 National (Nationwide) Inpatient Sample were studied. Patients diagnosed with pituitary tumors or disorders who had undergone transsphenoidal pituitary surgery were identified. Frailty was determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnoses indicator. Standard descriptive techniques and matched propensity score analyses were used to explore the odds ratios of postoperative complications, discharge dispositions, and costs. RESULTS: A total of 115,317 cases were included in the analysis. Frailty was present in 1.48% of cases. The mean age of frail versus non-frail patients was 57.14 ± 16.96 years (mean ± standard deviation) versus 51.91 ± 15.88 years, respectively (p < 0.001). A greater proportion of frail compared to non-frail patients had an age ≥ 65 years (37.08% vs 24.08%, respectively, p < 0.001). Frail patients were more likely to be black or Hispanic (p < 0.001), possess Medicare or Medicaid insurance (p < 0.001), belong to lower-median-income groups (p < 0.001), and have greater comorbidity (p < 0.001). Results of propensity score-matched multivariate analysis revealed that frail patients were more likely to develop fluid and electrolyte disorders (OR 1.61, 95% CI 1.07-2.43, p = 0.02), intracranial vascular complications (OR 2.73, 95% CI 1.01-7.49, p = 0.04), mental status changes (OR 3.60, 95% CI 1.65-7.82, p < 0.001), and medical complications including pulmonary insufficiency (OR 2.01, 95% CI 1.13-4.05, p = 0.02) and acute kidney failure (OR 4.70, 95% CI 1.88-11.74, p = 0.01). The mortality rate was higher among frail patients (1.46% vs 0.37%, p < 0.001). Frail patients also demonstrated a greater likelihood for nonroutine discharges (p < 0.001), higher mean total charges ($109,614.33 [95% CI $92,756.09-$126,472.50] vs $56,370.35 [95% CI $55,595.72-$57,144.98], p < 0.001), and longer hospitalizations (9.27 days [95% CI 7.79-10.75] vs 4.46 days [95% CI 4.39-4.53], p < 0.001). CONCLUSIONS: Frailty in patients undergoing transsphenoidal pituitary surgery is associated with worse postoperative outcomes and higher costs, indicating that state's potential role in routine preoperative risk stratification.

Assessment of the outcomes of the treatment of Cushing's disease in the hospitals of Castilla-La Mancha.

OBJECTIVE: Treatment of Cushing's disease poses interesting dilemmas in clinical practice. The aim of our study was to analyze the outcomes of the different treatments, the control and recurrence rates, and the complications derived from them. MATERIAL AND METHODS: Data were collected from the clinical records of 22 patients over 18 years of age (86.4% women). They had been diagnosed with Cushing's disease between 2000 and 2012, and were monitored at Complejo Hospitalario Universitario-Albacete, Hospital Virgen de la Salud-Toledo Hospital General Universitario de Ciudad Real, Hospital Virgen de la Luz-Cuenca, Hospital Nuestra Señora del Prado-Talavera de la Reina, and Complejo Hospitalario la Mancha Centro-Alcázar de San Juan. RESULTS: Surgery was the treatment of choice in all patients. Biochemical cure was achieved in 72.2% of patients. Nine patients developed in the early postoperative period diabetes insipidus, which became in 2 patients only. Surprisingly, 3 patients with normal postoperative neurohypophyseal function later developed permanent diabetes insipidus. New hormone deficiencies occurred in 7 patients. Seventeen patients received ketoconazole before surgery (5 of them after surgery also), and 70% of them achieved normal urinary free cortisol levels. Three patients also received radiotherapy, and all of them were cured after a median follow-up of 85.5 months; they developed no tumors or other complications. CONCLUSIONS: Our study reports the outcomes of management of Cushing's disease in non-reference centers for this disease, possibly giving a realistic picture of standard clinical practice for the condition in Spain.

Current trends in surgical approach and outcomes following pituitary tumor resection.

OBJECTIVES/HYPOTHESIS: The goals of pituitary tumor resection include normalizing endocrine function, relieving mass effect, and minimizing risk of recurrence. This study investigated current trends in costs and complications for transfrontal and transsphenoidal pituitary surgery. STUDY DESIGN: Retrospective review of the 2008-2011 Nationwide Inpatient Sample for patients undergoing pituitary lesion resection. METHODS: Demographics and outcomes were compared between transfrontal and transsphenoidal surgical approaches using χ(2) tests. Multivariate analysis was performed to investigate outcomes while controlling for confounders. RESULTS: There were 8,543 admissions for resection of pituitary lesions that met our inclusion criteria. Most (>90%) were treated transsphenoidally. The transfrontal approach was most frequent in the young (<35 years) and in the South. Rates of mortality and complications were higher in patients undergoing transfrontal surgery. Multivariate analysis found transsphenoidal resection was associated with a reduction in hospital costs and length of stay by over 50%; low-volume hospitals had increased cost and length of stay. There was an increased rate of transfrontal approaches at low-volume centers. CONCLUSIONS: Multiple factors influence outcomes of pituitary tumor resection. Transsphenoidal pituitary surgery is associated with a shorter length of stay, lower cost, and lower complication rates when compared to transfrontal surgery. Case specifics, including tumor location and size, influence approach and lead to a selection bias that cannot be controlled for in the present study. The prevalence of transfrontal resections at low-volume centers may indicate an area of further investigation. Additionally, when controlling for surgical approach, low-volume centers were found to adversely affect economic outcomes and also warrants investigation. LEVEL OF EVIDENCE: 2c.

Treatment-related morbidity and the management of pediatric craniopharyngioma: a systematic review.

OBJECT: Craniopharyngiomas are benign tumors but their close anatomical relationship with critical neurological, endocrine, and vascular structures makes gross-total resection (GTR) with minimal morbidity difficult to achieve. Currently, there is controversy regarding the extent, timing, and modality of treatment for pediatric craniopharyngioma. METHODS: The authors performed a systematic review of the published literature on pediatric craniopharyngioma to determine patterns of clinical practice and the reported outcomes of standard treatment strategies. This yielded 109 studies, which contained data describing extent of resection for a total of 531 patients. Differences in outcome were examined based upon extent of resection and choice of radiation treatment. RESULTS: Gross-total resection was associated with increased rates of new endocrine dysfunction (OR 5.4, p < 0.001), panhypopituitarism (OR 7.8, p = 0.006), and new neurological deficits (OR 9.9, p = 0.03) compared with biopsy procedures. Subtotal resection (STR) was not associated with an increased rate of new neurological deficits. Gross-total was associated with increased rates of diabetes insipidus (OR 7.7, p = 0.05) compared with the combination of STR and radiotherapy (RT). The addition of RT to STR was associated with increased rates of panhypopituitarism (OR 9.9, p = 0.01) but otherwise similar rates of morbidities. CONCLUSIONS: Although subject to the limitations of a literature review, this report suggests that GTR is associated with increased rates of endocrinopathies compared with STR + RT, and this should be considered when planning goals of surgery.

Pre-operative assessment of patients undergoing endoscopic, transnasal, transsphenoidal pituitary surgery.

OBJECTIVE: To demonstrate the importance of pre-operative ear, nose and throat assessment in patients undergoing endoscopic, transsphenoidal surgery for pituitary tumours. CASE REPORTS: Literature pertaining to the pre-operative otorhinolaryngological assessment and management of patients undergoing endoscopic anterior skull base surgery is sparse. We describe two cases from our series of 59 patients undergoing endoscopic pituitary surgery. The first case involved a young male patient with a large pituitary macroadenoma. His main complaint was visual impairment. He had no previous history of sinonasal pathology and did not complain of any nasal symptoms during the pre-operative neurosurgical assessment. At the time of surgery, a purulent nasal discharge was seen emanating from both middle meati. Surgery was abandoned due to the risk of post-operative meningitis, and postponed until the patient's chronic rhinosinusitis was optimally managed. The second patient was a 47-year-old woman with a large pituitary macroadenoma, who presented to the neurosurgical department with a main complaint of diplopia. She too gave no history of previous nasal problems, and she underwent uneventful surgery using the endoscopic, transnasal approach. Two weeks after surgery, she presented to the emergency unit with severe epistaxis. A previous diagnosis of hereditary haemorrhagic telangiectasia was discovered, and further surgical and medical intervention was required before the epistaxis was finally controlled. CONCLUSIONS: Pre-operative otorhinolaryngological assessment is essential prior to endoscopic pituitary or anterior skull base surgery. A thorough otorhinolaryngological history will determine whether any co-morbid diseases exist which could affect the surgical field. Nasal anatomy can be assessed via nasal endoscopy and sinusitis excluded. Computed tomography imaging is a valuable aid to decisions regarding additional procedures needed to optimise access to the pituitary fossa.

Assessment of the postoperative discomfort of intra-auricularly hypophysectomized rats.

Rats subjected to hypophysectomy make up one of the largest groups of experimental animals in Europe, since there is a legal demand for batch testing of industrially produced growth hormones. To describe the clinical performance of rats having undergone hypophysectomy, animals were examined postoperatively by monitoring behaviour, body temperature and food intake. Behavioural changes were observed in rats that had only been anaesthetized, as well as in sham-operated rats, while no behavioural deviations could be shown in hypophysectomized rats. On the first day after surgery all rats had declining body temperature and food intake; and this change was not reversed by treatment with carprofen, buprenorphine or oxytetracycline. The mortality rate in rats treated with buprenorphine was increased, as was the mortality rate in rats hypophysectomized when weighing more than 100 g. As there seemed to be no differences whether methohexital or a combination of fentanyl, fluanison and midazolam was used, the latter anaesthesia is recommended due to its analgesic potential. For post-surgical analgesic treatment, carprofen is recommended rather than buprenorphine. At best, the use of hypophysectomized rats should be replaced in industrial batch testing by an existing in vitro method.

[Assessment of prognosis factors in the cure of Cushing's disease surgically treated via a +septotransphenoidal approach]. / Evaluación de los factores pronósticos en la curación de la enfermedad de Cushing intervenida por vía septotransesfenoidal.

INTRODUCTION: In Cushing's disease (CD) pituitary surgery or radiotherapy has been proposed by some authors, when plasmatic cortisol after surgery is not clearly low. AIM: To assess if the different prognostic factors, specially plasmatic cortisol seven days after surgery and/or hypocortisolism phase are predictive of the CD outcome. METHODS: From 1988, 11 women with CD underwent 13 transsphenoidal microsurgery, because two patients relapsed. The mean age of patients was 27 years (11-52). Plasmatic cortisol was measured seven days after pituitary surgery, and since 45 days, every three-six months, basal plasmatic cortisol and after ACTH and urinary free cortisol were determined. RESULTS: Follow-up evaluations ranged from 18-84 months (median, 38 months). After pituitary surgery in 13 cases the cumulative remission was 100%, two cases relapsed. In 10 cases plasmatic cortisol seven days after surgery was less than 137 nmol/l and in three cases higher than 137 nmol/l. Three cases did not presented hypocortisolism phase. The two patients who relapsed, one was after eight months of pituitary surgery an previously showed low plasmatic cortisol and the other relapse 25 months after pituitary surgery without low cortisol plasmatic levels. CONCLUSION: Remission in CD can happen either low or normal plasmatic cortisol levels seven days posttreatment or without hypocortisolism phase. Ours findings ascribe new importance to the different presentations after treatment of CD, and patients with these findings are not a risk for relapse and pituitary surgery or irradiation would not be early indicated.

Assessment of endocrine function after transsphenoidal surgery for Cushing's disease.

OBJECTIVE: We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease. DESIGN: Five-year (mean) follow-up (range 1 month-12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24-hour urinary free cortisol. SETTING: Northern Ireland. SUBJECTS: Forty-one patients (33F: 8M); mean age at diagnosis 39.1 years (9-72 years). MAIN OUTCOME MEASURES: Measurements of early post-operative 0800 h serum cortisol and 24-hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24-hour urinary free cortisol measurements. Retrospective definition of cure. RESULTS: Twenty-seven patients were either cured or improved by surgery, 14 were considered definite failures. Of 19 patients cured, eight had unmeasurable early post-operative 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretion first diagnosed post-operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post-operatively. CONCLUSIONS: Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life-long endocrine therapy. Post-operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long-term monitoring of 24-hour urinary free cortisol is advisable.

Invasive v non-invasive assessment of the carotid arteries prior to trans-sphenoidal surgery.

Imaging studies in 47 patients who were to undergo trans-sphenoidal surgery were analysed with reference to the vascular structures in the parasellar region. The results of cavernous sinography, dynamic contrast enhanced Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) showed good correlation with each other and with the appearances found at operation. CT and MRI, both non-invasive investigations, are therefore reliable preliminary screening methods for identifying the small proportion of patients on whom other imaging techniques need to be performed.