Andrew S. Little

BACKGROUND AND OBJECTIVES: Craniopharyngiomas (CPs) recur in 20% to 50% of cases after initial management. To date, there are no large multi-institutional series investigating outcomes in patients receiving surgery for recurrent CP. Here, we leverage the Registry of Adenomas of the Pituitary and Related Disorders to analyze outcomes after surgical treatment of recurrent CP. METHODS: Demographic, clinical, radiographic, surgical, and outcome variables were analyzed for 483 patients receiving surgery for primary or recurrent CP across 16 US-based academic skull-base centers comprising the Registry of Adenomas of the Pituitary and Related Disorders consortium from 2000 to 2024. RESULTS: Among the 483 patients, 360 (74.5%) had primary CP and 123 (25.5%) had recurrent CP. The recurrent cohort was younger at initial diagnosis ( P _adj < .01) and recurrence ( P _adj = .02). Adamantinomatous CPs were more common in the recurrent cohort but not significantly so, and 33.3% of cases had prior radiation therapy. Recurrent cases had more frequent preoperative endocrine dysfunction and hormone replacement ( P _adj < .01). Patients with recurrent CP had less frequent suprasellar tumor extension ( P _adj = .04) and more frequent preinfundibular/transinfundibular over retroinfundibular localization ( P _adj = .02). There were no differences in operative approach; endoscopic endonasal surgery was the most common, and procedures achieved similar distributions of gross and subtotal resection in both cohorts ( P _adj = .30) with similar low frequencies of unplanned reoperation and surgical complications. New postoperative arginine vasopressin deficiency (in patients without preoperative arginine vasopressin deficiency) was more common in the primary cohort ( P _adj = .04), but long-term follow-up demonstrated similar frequencies of endocrine dysfunction in both cohorts and comparably low rates (P _adj = .17). CONCLUSION: This study provides the largest comparative evaluation of patients undergoing surgery for recurrent vs primary CP. Despite prior treatment, patients with recurrent CP achieved comparable resection outcomes with similar rates of neuroendocrine dysfunction. These findings indicate surgical resection remains a safe and efficacious option for recurrent CP, especially as emerging targeted therapies become available.

Disclosure: K.C. Yuen: Advisory Board Member; Self; Novo Nordisk, Ascendis, Corcept Therapeutics, Ipsen, Amryt, Strongbridge, Crinetics, Recordati, Xeris. Grant Recipient; Self; Corcept Therapeutics, Crinetics, Ascendis, Amryt. Speaker; Self; Corcept Therapeutics, Novo Nordisk, Recordati. E. Smith: None. F. Bernabe: None. J.M. Eschbacher: None. M. Rodriguez: None. A.S. Little: None. Background: Acidophil stem cell adenomas (ASCAs) are tumors derived from a precursor of somatotrophs and lactotrophs. Often presenting clinically like prolactinomas that respond to dopamine agonist therapy, some may also present with subtle clinical symptoms and biochemical features of acromegaly. Because ASCAs are so rare, their clinicopathological features have not been well-studied. Aims: Clinicopathological features of ASCAs were analyzed and compared with mixed somatotroph-lactotroph adenomas (MSLAs), mammosomatotroph adenomas (MSAs) and pure somatotroph adenomas (PSAs). Methods: We retrospectively reviewed the medical records of acromegaly patients from a single institution presenting from 2001 to 2022. All growth hormone-secreting adenomas were categorized into ASCAs, MSLAs, MSAs and PSAs based on their histopathological findings in surgically treated patients, and their pre- (preop) and post-operative (postop) clinical data were analyzed. Results: Among 135 patients within this cohort, ASCAs, MLSAs, MSAs and PSAs accounted for 21 (15.5%), 11 (8.1%), 59 (43.7%) and 44 (32.6%) cases, respectively. ASCA patients were younger (mean age ASCA: 48.6 vs MLSA 56.5, MSA 59.0, PSA 63.4 years; P < 0.05), had higher preop prolactin levels (ASCA: 1190 ± 639.0 vs MSLA: 44.9 ± 23.2, MSA: 39.7 ± 6.8, PSA: 23.8 ± 5.5 µg/L; P < 0.01), had higher rates of MIB-1 labeling indices (ASCA 76.2% vs MSLA 39.0%, MSA 45.5%, PSA 43.2%; P < 0.05) and preop visual field defect (VFD) (ASCA 32.3% vs MSLA 13.6%, MSA 27.3%, PSA 29.6%; P < 0.05), and had lower rates of preop hypertension (HTN) (ASCA 14.3% vs MSLA 52.5%, MSA 36.4%, PSA 31.8%; P < 0.05) and diabetes mellitus (DM) (ASCA 14.3% vs MSLA 27.2%, MSA 54.5%, PSA 20.5%; P < 0.05). ASCA tumors were larger than MSAs (2.3 ± 1.0 vs 1.6 ± 0.7 cm; P < 0.01), but comparable to MSLAs and PSAs. Rates of cavernous sinus invasion and preop GH levels were similar between groups. Postop GH levels were higher in ASCA (8.6 ± 5.3 µg/L) compared to MSLAs (2.4 ± 0.5 µg/L) and MSAs (1.1 ± 0.7 µg/L) (P < 0.05). ASCA preop IGF-I levels were lower than PSA (ASCA: 466.7 ± 118.5 vs PSA: 803.7 ± 56.5 µg/L; P < 0.05), while postop IGF-I levels were comparable to MLSAs, MSAs and PSAs. ASCAs also had lower postop remission rates compared to MLSAs, MSAs and PSAs (ASCA 19.0% vs MLSA 45.5%, MSA 38.6% and PSA 54.2%; P < 0.05). Most ASCA (85.7%), MLSA (81.4%), MSA (100%) and PSA (77.2%) patients underwent one surgery and more ASCA (23.8%), MLSA (25.4%) and PSA (22.7%) patients underwent radiation therapy than MSA (9.1%) patients. Conclusions: Our data demonstrated important insights into the differences of clinicopathological features of ASCAs compared to other acromegaly subtypes. Notably, ASCAs occurred in younger patients, had larger and more aggressive tumors, had lower postop remission rates and had higher VFD rates. In addition, ASCAs had higher rates of preop hyperprolactinemia and lower rates of preop HTN and DM. Presentation: Thursday, June 15, 2023

(1) Background: Cushing’s disease (CD) is a serious endocrine disorder caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary neuroendocrine tumor (PitNET) that stimulates the adrenal glands to overproduce cortisol. Chronic exposure to excess cortisol has detrimental effects on health, including increased stroke rates, diabetes, obesity, cognitive impairment, anxiety, depression, and death. The first-line treatment for CD is pituitary surgery. Current surgical remission rates reported in only 56% of patients depending on several criteria. The lack of specificity, poor tolerability, and low efficacy of the subsequent second-line medical therapies make CD a medical therapeutic challenge. One major limitation that hinders the development of specific medical therapies is the lack of relevant human model systems that recapitulate the cellular composition of PitNET microenvironment. (2) Methods: human pituitary tumor tissue was harvested during transsphenoidal surgery from CD patients to generate organoids (hPITOs). (3) Results: hPITOs generated from corticotroph, lactotroph, gonadotroph, and somatotroph tumors exhibited morphological diversity among the organoid lines between individual patients and amongst subtypes. The similarity in cell lineages between the organoid line and the patient’s tumor was validated by comparing the neuropathology report to the expression pattern of PitNET specific markers, using spectral flow cytometry and exome sequencing. A high-throughput drug screen demonstrated patient-specific drug responses of hPITOs amongst each tumor subtype. Generation of induced pluripotent stem cells (iPSCs) from a CD patient carrying germline mutation CDH23 exhibited dysregulated cell lineage commitment. (4) Conclusions: The human pituitary neuroendocrine tumor organoids represent a novel approach in how we model complex pathologies in CD patients, which will enable effective personalized medicine for these patients.

Background The HOT-HMV study in 2017 demonstrated that patients with persistent hypercapnia following an exacerbation of chronic obstructive pulmonary disease (COPD) who received home non-invasive ventilation (NIV) benefitted from prolonged time to readmission. Advance care planning (ACP) is recognised as being able to improve palliative care outcomes for patients with COPD. This study aimed to explore the benefits of and barriers to ACP in patients with COPD on home-NIV and how barriers might be addressed. Methods Semi-structured qualitative interviews were conducted with health care professionals (HCP) from the North East Assisted Ventilation Service (NEAVS) (12 interviews) and with patients (11 interviews). Interviews were analysed using the principles of thematic analysis. Results The findings emphasised the importance of ACP whilst also raising a number of challenges. NEAVS is a regional service therefore multiple local teams are also involved in patient care, resulting in a lack of clarity of responsibility for ACP conversations and geographical disparity with care continuity. HCP felt COPD patients were an under-served group both in medicine and society. They often have an uncertain disease trajectory resulting in difficulty in ascertaining appropriate timing for initiation of conversations. The patient group gave insights into the factors that affected their engagement in ACP discussions including high levels of anxiety and communication factors, notably a reduction in face-to-face consultations due to Covid-19. Conclusions This study allowed us to map out many of the perceived challenges facing patients with COPD on home-NIV in carrying out meaningful and timely ACP. Being conscious of the challenges allows a deeper understanding and awareness of the importance of individualised ACP discussions. The study supports a review of the structure of similar services to formally incorporate ACP and assign responsibility. Formal palliative care involvement is also suggested, to provide both education for HCP and direct patient input.

For a structural material which suffers elastic failure, there are many different theories of elastic failure. Unfortunately, not all these theories make the same predictions. Moreover, some of these theories are good for materials such as mild steel, which has a definite yield point, while others are more satisfactory for brittle materials, such as cast iron. Also, for materials such as composites, the theories of elastic failure are very much more complex. The theories can also be affected by the complex combination of stresses that occur on the structure. For these reasons, a study of the theories of elastic failure is important, and many of them are presented in this chapter. The theories of elastic failure for composites are given in Chapter 18.

The torsion of shafts appears in a number of different branches of engineering, including propeller shafts for ships and aircraft, shafts driving the blades of a helicopter, shafts driving the rear wheels of an automobile and shafts driving food mixers, washing machines, tumble dryers, dishwashers, and so on. If the shaft is overstressed due to a torque, so that the maximum shear stress in the shaft exceeds the yield shear stress of the shaft’s material, the shaft can fracture. This is an undesirable phenomenon and normally it should be designed out; hence the need for the theory contained in this chapter. The twisting of shafts is very important for designing the propulsion systems for ships, automobiles, helicopters, and also for food mixers, etc. Torsion is also important when a rolled steel joint is connected to another rolled steel joint which is at right angles to it, and out-of-plane. In this case if one beam bends, it can transmit a torque to the other beam, but this phenomenon is beyond the scope of this text.

Objectives/Hypothesis: Sinonasal Outcomes Test‐22 (SNOT‐22) is used widely as a patient‐reported sinonasal quality‐of‐life (QOL) instrument for endoscopic endonasal pituitary surgery. However, it has never been validated in this population. This study explores the psychometric validity of SNOT‐22 to determine if it is a valid scale in patients undergoing endoscopic pituitary surgery.Study Design: Multicenter prospective trial.Methods: Adult patients (n = 113) with pituitary tumors undergoing endoscopic surgery were enrolled in a multicenter study. Patient‐reported QOL was assessed using SNOT‐22 and the Anterior Skull Base Nasal Inventory‐12. Face validity, internal consistency, responsiveness to clinical change, test–retest reliability, and concurrent validity were determined using standard statistical methods.Results: Internal consistency using Cronbach's alpha at baseline and 2 weeks postoperatively were 0.911 and 0.922, indicating SNOT‐22 performed well as a single construct. Mean QOL scores were significantly worse at 2 weeks than baseline (16.4 ± 15.1 vs. 23.1 ± 16.4, P < .001), indicating the scale is responsive to clinical change. However, only 11/22 items demonstrated significant changes in mean scores at 2 weeks. Correlation between scores at 2 and 3 weeks was high, suggesting good test–retest reliability, r(107) = 0.75, P < .001. Factor analysis suggests the five‐factor solution proposed for the SNOT‐22 in rhinosinusitis patients is not valid in pituitary surgery patients.Conclusions: The SNOT‐22 is a valid QOL instrument in patients undergoing endoscopic pituitary surgery. However, because it includes 22 items, can be applied only as a single construct, 50% of the items do not demonstrate changes after surgery, and is not as sensitive to change as other scales, shorter instruments developed specifically for this patient population may be preferable.Level of Evidence: 2 Laryngoscope, 131:E2757–E2763, 2021

Introduction: Sinonasal morbidity following endoscopic endonasal approaches for pituitary tumors is an important determinant of patient recovery after surgery. Efforts to assess sinonasal quality of life (QOL) have been limited by largely retrospective, single-surgeon, single-center studies without predefined follow-up intervals. The purpose of this multicenter, prospective outcomes study was to identify early and late predictors of sinonasal QOL following endoscopic endonasal pituitary surgery (EEPS) and to evaluate return to baseline sinonasal QOL. Methods: Adult patients with pituitary lesions undergoing standard endoscopic transsphenoidal surgery were eligible. Patient-reported sinonasal QOL was assessed at baseline, 2 weeks (early) and through 12 weeks (late) after pituitary surgery using the Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12), a site-specific QOL instrument developed and validated in endoscopic endonasal pituitary. Adult patients were enrolled in a multicenter QOL study (NCT03014687). Univariate and multivariable analyses were conducted to identify predictors of QOL after surgery. Exploratory covariates included demographics, tumor characteristics, medical history, social history, and surgical techniques. Results: 113 adult patients treated at 3 centers by 4 neurosurgeons and 9 otolaryngologists were included ([Fig. 1]). In a univariate analysis, predictors of improved early sinonasal QOL included no sinusitis (13.35 ± 8.48 vs. 24.5 ± 13.6, p = 0.015) and baseline QOL score (r (108) = 0.199, p = 0.04, Pearson's correlation). Predictors of improved late QOL included no history of headaches (4.8 ± 6.2 vs 7.8 ± 8.53, p = 0.04) and not undergoing a nasal debridement (3.23 ± 4.46 vs. 6.68 ± 7.68, p = 0.02). Multivariable analysis using ANOVA and logistic regression identified no predictors of QOL at either time point. At 2 weeks postoperatively, sinonasal QOL in 43/113 (38.1%) patients had either returned to baseline or improved. By 12 weeks, sinonasal QOL in 80/113 (70.8%) patients had either retuned to baseline or improved. Conclusion: In this multicenter, prospective QOL study, we identified no specific predictors of sinonasal QOL at 12 weeks in a multivariable analysis, suggesting that the nasal cavity has robust capacity to heal in a variety of clinical contexts. Most patients report a return to or improvement beyond baseline QOL at 12 weeks after surgery. Publication Date: 12 February 2021 (online) © 2021. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany