Transnasal transsphenoidal pituitary surgery in a large tertiary hospital, a retrospective study.

OBJECTIVES: Pituitary adenomas (PAs), although being small tumours, can have quite an impact on patients' lives causing hormonal and visual disturbances, for which surgery must be performed. As a large peripheral hospital with specialists in pituitary surgery, an assessment of the efficacy and safety of transnasal transsphenoidal pituitary surgery was made. METHODS: A retrospective analysis of neurosurgical reports as well as pre and postoperative imaging was made to evaluate the presenting symptoms, tumoural variables, peri-operative morbidity, and long-term outcome. RESULTS: This cohort included 105 patients who were operated for PAs over a 9-year period, with a slight male predominance. Adenomas had a mean maximum diameter of almost 25 mm, with one-third of tumours presenting with a Knosp-grade 3 or 4. As expected, most patients presented with either visual (32.4%) or hormonal (40.0%) disturbances. After surgery, 85.3% had complete resolution of visual deficits, and 97.1% had normalisation of hormonal hypersecretion. Postoperative hormonal insufficiency requiring substitution was observed in 43.1% and was significantly more frequent in males and in non-functioning pituitary adenomas (NFAs). Postoperative cerebrospinal fluid (CSF) leakage was observed in 2.9%, and merely one patient developed meningitis. Tumour recurrence was significantly more frequent in patients with partial resection as compared to complete resection (25.6 vs. 7.9%). CONCLUSIONS: This study demonstrates that transnasal transsphenoidal pituitary surgery can be performed safely and effectively in a large non-university hospital, improving visual and/or hormonal disturbances as well as providing long-term tumour control. Patients with larger adenomas are at an increased risk to develop postoperative hypopituitarism.

Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study.

BACKGROUND: Awake mapping has been associated with decreased neurological deficits and increased extent of resection in eloquent glioma resections. However, its effect within clinically relevant glioblastoma subgroups remains poorly understood. We aimed to assess the benefit of this technique in subgroups of patients with glioblastomas based on age, preoperative neurological morbidity, and Karnofsky Performance Score (KPS). METHODS: In this propensity score-matched analysis of an international, multicentre, cohort study (GLIOMAP), patients were recruited at four tertiary centres in Europe (Erasmus MC, Rotterdam and Haaglanden MC, The Hague, Netherlands, and UZ Leuven, Leuven, Belgium) and the USA (Brigham and Women's Hospital, Boston, MA). Patients were eligible if they were aged 18-90 years, undergoing resection, had a histopathological diagnosis of primary glioblastoma, their tumour was in an eloquent or near-eloquent location, and they had a unifocal enhancing lesion. Patients either underwent awake mapping during craniotomy, or asleep resection, as per treating physician or multidisciplinary tumour board decision. We used propensity-score matching (1:3) to match patients in the awake group with those in the asleep group to create a matched cohort, and to match patients from subgroups stratified by age (<70 years vs ≥70 years), preoperative National Institute of Health Stroke Scale (NIHSS) score (score of 0-1 vs ≥2), and preoperative KPS (90-100 vs ≤80). We used Cox proportional hazard regressions to analyse the effect of awake mapping on the primary outcomes including postoperative neurological deficits (measured by deterioration in NIHSS score at 6 week, 3 months, and 6 months postoperatively), overall survival, and progression-free survival. We used logistic regression to analyse the predictive value of awake mapping and other perioperative factors on postoperative outcomes. FINDINGS: Between Jan 1, 2010, and Oct 31, 2020, 3919 patients were recruited, of whom 1047 with tumour resection for primary eloquent glioblastoma were included in analyses as the overall unmatched cohort. After propensity-score matching, the overall matched cohort comprised 536 patients, of whom 134 had awake craniotomies and 402 had asleep resection. In the overall matched cohort, awake craniotomy versus asleep resection resulted in fewer neurological deficits at 3 months (26 [22%] of 120 vs 107 [33%] of 323; p=0·019) and 6 months (30 [26%] of 115 vs 125 [41%] of 305; p=0·0048) postoperatively, longer overall survival (median 17·0 months [95% CI 15·0-24·0] vs 14·0 months [13·0-16·0]; p=0·00054), and longer progression-free survival (median 9·0 months [8·0-11·0] vs 7·3 months [6·0-8·8]; p=0·0060). In subgroup analyses, fewer postoperative neurological deficits occurred at 3 months and at 6 months with awake craniotomy versus asleep resection in patients younger than 70 years (3 months: 22 [21%] of 103 vs 93 [34%] of 272; p=0·016; 6 months: 24 [24%] of 101 vs 108 [42%] of 258; p=0·0014), those with an NIHSS score of 0-1 (3 months: 22 [23%] of 96 vs 97 [38%] of 254; p=0·0071; 6 months: 27 [28%] of 95 vs 115 [48%] of 239; p=0·0010), and those with a KPS of 90-100 (3 months: 17 [19%] of 88 vs 74 [35%] of 237; p=0·034; 6 months: 24 [28%] of 87 vs 101 [45%] of 223, p=0·0043). Additionally, fewer postoperative neurological deficits were seen in the awake group versus the asleep group at 3 months in patients aged 70 years and older (two [13%] of 16 vs 15 [43%] of 35; p=0·033; no difference seen at 6 months), with a NIHSS score of 2 or higher (3 months: three [13%] of 23 vs 21 [36%] of 58; p=0·040) and at 6 months in those with a KPS of 80 or lower (five [18%] of 28 vs 34 [39%] of 88; p=0·043; no difference seen at 3 months). Median overall survival was longer for the awake group than the asleep group in the subgroups younger than 70 years (19·5 months [95% CI 16·0-31·0] vs 15·0 months [13·0-17·0]; p<0·0001), an NIHSS score of 0-1 (18·0 months [16·0-31·0] vs 14·0 months [13·0-16·5]; p=0·00047), and KPS of 90-100 (19·0 months [16·0-31·0] vs 14·5 months [13·0-16·5]; p=0·00058). Median progression-free survival was also longer in the awake group than in the asleep group in patients younger than 70 years (9·3 months [95% CI 8·0-12·0] vs 7·5 months [6·5-9·0]; p=0·0061), in those with an NIHSS score of 0-1 (9·5 months [9·0-12·0] vs 8·0 months [6·5-9·0]; p=0·0035), and in those with a KPS of 90-100 (10·0 months [9·0-13·0] vs 8·0 months [7·0-9·0]; p=0·0010). No difference was seen in overall survival or progression-free survival between the awake group and the asleep group for those aged 70 years and older, with NIHSS scores of 2 or higher, or with a KPS of 80 or lower. INTERPRETATION: These data might aid neurosurgeons with the assessment of their surgical strategy in individual glioblastoma patients. These findings will be validated and further explored in the SAFE trial (NCT03861299) and the PROGRAM study (NCT04708171). FUNDING: None.

Non-occlusive mesenteric ischemia: two case reports and a short review of the literature.

INTRODUCTION: Non-occlusive mesenteric ischemia (NOMI) is an infrequent cause of acute mesenteric ischemia with atypical symptoms and a high mortality. PATIENTS AND METHODS: We report two cases of NOMI characterized by their difference in etiology, treatment and outcome. RESULTS: In the first case, the patient developed NOMI after septic shock, she was successfully treated with surgery. The second patient experienced two episodes of cardiac arrest followed by NOMI. He received only supportive care and died shortly after. We present a short review of the literature, discussing epidemiology, pathophysiology, clinical presentations, diagnosis and management of NOMI. CONCLUSION: NOMI is a rare disease with a difficult diagnosis. Early recognition and treatment with supportive therapy, vasodilator drugs and possibly surgery can significantly lower mortality.

Impact of maximal extent of resection on postoperative deficits, patient functioning, and survival within clinically important glioblastoma subgroups.

BACKGROUND: The impact of extent of resection (EOR), residual tumor volume (RTV), and gross-total resection (GTR) in glioblastoma subgroups is currently unknown. This study aimed to analyze their impact on patient subgroups in relation to neurological and functional outcomes. METHODS: Patients with tumor resection for eloquent glioblastoma between 2010 and 2020 at 4 tertiary centers were recruited from a cohort of 3919 patients. RESULTS: One thousand and forty-seven (1047) patients were included. Higher EOR and lower RTV were significantly associated with improved overall survival (OS) and progression-free survival (PFS) across all subgroups, but RTV was a stronger prognostic factor. GTR based on RTV improved median OS in the overall cohort (19.0 months, P < .0001), and in the subgroups with IDH wildtype tumors (18.5 months, P = .00055), MGMT methylated tumors (35.0 months, P < .0001), aged <70 (20.0 months, P < .0001), NIHSS 0-1 (19.0 months, P = .0038), KPS 90-100 (19.5 months, P = .0012), and KPS ≤80 (17.0 months, P = .036). GTR was significantly associated with improved OS in the overall cohort (HR 0.58, P = .0070) and improved PFS in the NIHSS 0-1 subgroup (HR 0.47, P = .012). GTR combined with preservation of neurological function (OFO 1 grade) yielded the longest survival times (median OS 22.0 months, P < .0001), which was significantly more frequently achieved in the awake mapping group (50.0%) than in the asleep group (21.8%) (P < .0001). CONCLUSIONS: Maximum resection was especially beneficial in the subgroups aged <70, NIHSS 0-1, and KPS 90-100 without increasing the risk of postoperative NIHSS or KPS worsening. These findings may assist surgical decision making in individual glioblastoma patients.

Exploring stem cell biology in pituitary tumors and derived organoids.

Pituitary tumorigenesis is highly prevalent and causes major endocrine disorders. Hardly anything is known on the behavior of the local stem cells in this pathology. Here, we explored the stem cells' biology in mouse and human pituitary tumors using transcriptomic, immunophenotyping and organoid approaches. In the prolactinoma-growing pituitary of dopamine receptor D2 knock-out mice, the stem cell population displays an activated state in terms of proliferative activity and distinct cytokine/chemokine phenotype. Organoids derived from the tumorous glands' stem cells recapitulated these aspects of the stem cells' activation nature. Upregulated cytokines, in particular interleukin-6, stimulated the stem cell-derived organoid development and growth process. In human pituitary tumors, cells typified by expression of stemness markers, in particular SOX2 and SOX9, were found present in a wide variety of clinical tumor types, also showing a pronounced proliferative status. Organoids efficiently developed from human tumor samples, displaying a stemness phenotype as well as tumor-specific expression fingerprints. Transcriptomic analysis revealed fading of cytokine pathways at organoid development and passaging, but their reactivation did not prove capable of rescuing early organoid expansion and passageability arrest. Taken together, our study revealed and underscored an activated phenotype of the pituitary-resident stem cells in tumorigenic glands and tumors. Our findings pave the way to defining the functional position of the local stem cells in pituitary tumor pathogenesis, at present barely known. Deeper insight can lead to more efficient and targeted clinical management, currently still not satisfactorily.