OBJECT: An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade. METHODS: The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas. RESULTS: The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas. CONCLUSIONS: The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.

OBJECTIVE: Parasellar growth is one of the most important prognostic variables of pituitary adenoma surgery, with adenomas regarded as not completely resectable if they invade the cavernous sinus (CS) but potentially curable if they displace CS structures. This study was conducted to correlate surgical treatment options and outcomes to the different biological behaviors (invasion vs displacement) of adenomas with parasellar extension into the superior or inferior CS compartments or completely encasing the carotid artery (Knosp high grades 3A, 3B, and 4).METHODS: This was a retrospective cohort analysis of 106 consecutive patients with Knosp high-grade pituitary adenomas with parasellar extension who underwent surgery via a primary endoscopic transsphenoidal approach between 2003 and 2017. Biological tumor characteristics (surgical status of invasiveness and tumor texture, 2017 WHO classification, proliferation rate), extent of resection, and complication rate were correlated with parasellar extension grades 3A, 3B, and 4 on preoperative MRI studies.RESULTS: Invasiveness was significantly less common in grade 3A (44%) than in grade 3B (72%, p = 0.037) and grade 4 (100%, p < 0.001) adenomas. Fibrous tumor texture was significantly more common in grade 4 (52%) compared to grade 3A (20%, p = 0.002), but not compared to grade 3B (28%) adenomas. Functioning macroadenomas had a significantly higher rate of invasiveness than nonfunctioning adenomas (91% vs 55%, p = 0.002). Mean proliferation rate assessed by MIB-1 was > 3% in all groups but without significant difference between the groups (grade 3A, 3.2%; 3B, 3.9%; 4, 3.7%). Rates of endocrine remission/gross-total resection were significantly higher in grade 3A (64%) than in grade 3B (33%, p = 0.021) and grade 4 (0%, p < 0.001) adenomas. In terms of complication rates, no significant difference was observed between grades.CONCLUSIONS: According to the authors’ data, the biological behavior of pituitary adenomas varies significantly between parasellar extension patterns. Adenomas with extension into the superior CS compartment have a lower rate of invasive growth than adenomas extending into the inferior CS compartment or encasing the carotid artery. Consequently, a significantly higher rate of remission can be achieved in grade 3A than in grade 3B and grade 4 adenomas. Therefore, the distinction into grades 3A, 3B, and 4 is of importance for prediction of adenoma invasion and surgical treatment considerations.

OBJECTIVE: Robotic devices have recently been introduced in stereotactic neurosurgery in order to overcome the limitations of frame-based and frameless techniques in terms of accuracy and safety. The aim of this study is to evaluate the feasibility and accuracy of the novel, miniature, iSYS1 robotic guidance device in stereotactic neurosurgery. METHODS: A preclinical phantom trial was conducted to compare the accuracy and duration of needle positioning between the robotic and manual technique in 162 cadaver biopsies. Second, 25 consecutive cases of tumor biopsies and intracranial catheter placements were performed with robotic guidance to evaluate the feasibility, accuracy, and duration of system setup and application in a clinical setting. RESULTS: The preclinical phantom trial revealed a mean target error of 0.6 mm (range 0.1–0.9 mm) for robotic guidance versus 1.2 mm (range 0.1–2.6 mm) for manual positioning of the biopsy needle (p < 0.001). The mean duration was 2.6 minutes (range 1.3–5.5 minutes) with robotic guidance versus 3.7 minutes (range 2.0–10.5 minutes) with manual positioning (p < 0.001). Clinical application of the iSYS1 robotic guidance device was feasible in all but 1 case. The median real target error was 1.3 mm (range 0.2–2.6 mm) at entry and 0.9 mm (range 0.0–3.1 mm) at the target point. The median setup and instrument positioning times were 11.8 minutes (range 4.2–26.7 minutes) and 4.9 minutes (range 3.1–14.0 minutes), respectively. CONCLUSIONS: According to the preclinical data, application of the iSYS1 robot can significantly improve accuracy and reduce instrument positioning time. During clinical application, the robot proved its high accuracy, short setup time, and short instrument positioning time, as well as demonstrating a short learning curve.

Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent ³¹ P/ ¹ H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Background: Current standard treatment of microprolactinomas is dopamine agonist therapy. As this drug treatment is lifelong in up to 80% of cases, many patients consult pituitary surgeons regarding a surgical alternative.Objective: To identify prognostic criteria for surgical remission, we reviewed outcomes of our series of microprolactinomas treated with endoscopic transsphenoidal surgery, with a special emphasis on magnetic resonance adenoma delineation and position.Methods: Our study cohort comprises a single center series of 60 patients operated for histopathologically verified magnetic resonance imaging unequivocally identifiable endosellar microprolactinoma between 2003 and 2017. In 31 patients the adenoma was enclosed by pituitary gland (group ENC), in 29 patients the adenoma was located lateral to the gland adherent to the medial cavernous sinus wall (group LAT).Results: After a mean follow-up of 37 mo (range 4-143 mo), remission rate was significantly higher in adenomas enclosed by pituitary gland (group ENC) than adenomas located lateral to the gland (group LAT), with 87% vs 45%,P = .01. Intraoperatively, 4 patients showed signs of invasiveness. Preoperative prolactin levels did not differ between the groups (mean 155 and 187 ng/ml in group ENC and LAT, respectively).A binary logistic regression model revealed that only the radiological criteria applied showed a significant correlation (P = .003) with endocrine remission.CONCLUSION: According to our results, remission rate is significantly higher in microprolactinomas enclosed by the pituitary gland. However, the decision for surgery should take into account surgeons experience and possibility of complications.

OBJECTIVE: As decisions regarding tumor diagnosis and subsequent treatment are increasingly based on molecular pathology, the frequency of brain biopsies is increasing. Robotic devices overcome limitations of frame-based and frameless techniques in terms of accuracy and usability. The aim of the present study was to present a novel, minimally invasive, robot-guided biopsy technique and compare the results with those of standard burr hole biopsy.METHODS: A tubular minimally invasive instrument set was custom-designed for the iSYS-1 robot-guided biopsies. Feasibility, accuracy, duration, and outcome were compared in a consecutive series of 66 cases of robot-guided stereotactic biopsies between the minimally invasive (32 patients) and standard (34 patients) procedures.RESULTS: Application of the minimally invasive instrument set was feasible in all patients. Compared with the standard burr hole technique, accuracy was significantly higher both at entry (median 1.5 mm [range 0.2–3.2 mm] vs 1.7 mm [range 0.8–5.1 mm], p = 0.008) and at target (median 1.5 mm [range 0.4–3.4 mm] vs 2.0 mm [range 0.8–3.9 mm], p = 0.019). The incision-to-suture time was significantly shorter (median 30 minutes [range 15–50 minutes] vs 37.5 minutes [range 25–105 minutes], p < 0.001). The skin incision was significantly shorter (median 16.3 mm [range 12.7–23.4 mm] vs 28.4 mm [range 20–42.2 mm], p = 0.002). A diagnostic tissue sample was obtained in all cases.CONCLUSIONS: Application of the novel instrument set was feasible in all patients. According to the authors’ data, the minimally invasive robot-guidance procedure can significantly improve accuracy, reduce operating time, and improve the cosmetic result of stereotactic biopsies.