RESUMO
OBJECTIVE: Dumbbell-shaped pituitary adenomas (DSPAs) are a subgroup of macroadenomas with suprasellar extension that are characterized by a smaller diameter at the level of the diaphragma sellae opening compared with the supradiaphragmal tumor component (SDTC). Hence, DSPAs may be particularly prone to a nondescending suprasellar tumor component and risk for residual tumor or postoperative bleeding. METHODS: A multicenter retrospective cohort analysis of 99 patients with DSPA operated on via direct endoscopic endonasal transsphenoidal approach between 2011 and 2020 was conducted. Patient recruitment was performed at two tertiary care centers (Medical University of Vienna and University of Southern California) with expertise in endoscopic skull base surgery. DSPA was defined as having a smaller diameter at the level of the diaphragma sellae compared with the SDTC. RESULTS: On preoperative MRI, all DSPAs were macroadenomas (maximum diameter range 17-71 mm, volume range 2-88 cm3). Tumor descent was found in 73 (74%) of 99 patients (group A), and nondescent in 26 (26%) of 99 patients (group B) intraoperatively. DSPAs in group A had a significantly smaller diameter (30 vs 42 mm, p < 0.001) and significantly smaller volume (10 vs 22 cm3, p < 0.001) than those in group B. The ratio of the minimum area at the level of the diaphragmal opening in comparison with the maximum area of the suprasellar tumor component ("neck-to-dome area") was significantly lower in group A than in group B (1.7 vs 2.7, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.75 (95% CI 0.63-0.87). At a cutoff ratio of 1.9, the sensitivity and specificity for a nondescending suprasellar tumor component were 77% and 34%, respectively. CONCLUSIONS: In the present study, the neck-to-dome area ratio was of prognostic value for prediction of intraoperative tumor nondescent in DSPAs operated on via a direct endonasal endoscopic approach. Pituitary adenoma SDTC nondescent carried the inherent risk of hemorrhagic transformation in all cases.
RESUMO
OBJECTIVE: Several single-nucleotide polymorphisms have been identified to be disadvantageous or protective in regard to disease severity in patients with non-alcoholic fatty liver disease (NAFLD). However, it is unclear, whether including genetic risk factor(s) either alone or combined into risk stratification algorithms for NAFLD actually provides incremental benefit over clinical risk factors. DESIGN: Patients with biopsy-proven NAFLD were genotyped for the PNPLA3-rs738409(minor allele:G), TM6SF2-rs58542926(minor allele:T) and HSD17B13- rs72613567 (minor allele:TA) variants. The NAFLD activity score (NAS) and fibrosis stage (F0-F4) were used to grade and stage all liver biopsy samples. Patients from seven centers throughout Central Europe were considered for the study. RESULTS: 703 patients were included: NAS ≥ 5:173(24.6%); Fibrosis: F3-4:81(11.5%). PNPLA3 G/G genotype was associated with a NAS ≥ 5(aOR 2.23, p = 0.007) and advanced fibrosis (aOR-3.48, p < 0.001).TM6SF2 T/- was associated with advanced fibrosis (aOR 1.99, p = 0.023). HSD17B13 TA/- was associated with a lower probability of NAS ≥ 5(TA/T: aOR 0.65, p = 0.041, TA/TA: aOR 0.40, p = 0.033). Regarding the predictive capability for NAS ≥ 5, well-known risk factors (age, sex, BMI, diabetes, and ALT; baseline model) had an AUC of 0.758, Addition of PNPLA3(AUC 0.766), HSB17B13(AUC 0.766), and their combination(AUC 0.775), but not of TM6SF2(AUC 0.762), resulted in a higher diagnostic accuracy of the model. Addition of genetic markers for the prediction of advanced fibrosis (baseline model: age, sex, BMI, diabetes: AUC 0.777) resulted in a higher AUC if PNPLA3(AUC 0.789), and TM6SF2(AUC 0.786) but not if HSD17B13(0.777) were added. CONCLUSION: In biopsy-proven NAFLD, PNPLA3 G/-, TM6SF2 T/- and HSD17B13 TA/- carriage are associated with severity of NAFLD. Incorporating these genetic risk factors into risk stratification models might improve their predictive accuracy for severity of NAFLD and/or advanced fibrosis on liver biopsy.