Prognostic factors of biochemical remission after transsphenoidal surgery for acromegaly: a structured review

Object Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI. Methods A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors' institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension. Results The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown. Conclusions The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.

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Predictors for remission after transsphenoidal surgery in acromegaly: a Dutch multicenter study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab069 ◽

2021 ◽

Author(s):

Eva C Coopmans ◽

Mark R Postma ◽

Thalijn L C Wolters ◽

Sebastiaan W F van Meyel ◽

Romana Netea-Maier ◽

...

Keyword(s):

Multicenter Study ◽

Transsphenoidal Surgery ◽

Early Stage ◽

Primary Treatment ◽

Postoperative Treatment ◽

Tumor Diameter ◽

Total N ◽

Maximum Tumor Diameter ◽

Biochemical Remission

Abstract Context Transsphenoidal surgery (TSS) is the primary treatment of choice in acromegaly. It is important to identify patients in whom surgical cure is not attainable at an early stage, both to inform patients on expected treatment outcome and to select those who are more likely to need additional therapy. Objective To identify predictors for remission after TSS in acromegaly. Design Large multicenter study with retrospective data collection from three tertiary neurosurgical referral centers in the Netherlands. Methods We analyzed clinical data since 2000 from three cohorts (Groningen, Nijmegen and Rotterdam, total n=282). Multivariate regression models were used to identify predictors of early biochemical remission (12 weeks-1 year postoperatively) according to the 2010 consensus criteria, long-term remission (age- and sex normalized IGF-1 and the absence of postoperative treatment until last follow-up) and relative IGF-1 and GH reduction. Results A larger maximum tumor diameter (OR 0.91, 95% CI 0.87–0.96, p≤0.0001) was associated with a lower chance of early biochemical remission. A larger maximum tumor diameter (OR 0.93, 95% CI 0.89–0.97, p=0.0022) and a higher random GH concentration at diagnosis (OR 0.98, 95% CI 0.96–0.99, p=0.0053) were associated with a lower chance of long-term remission. Conclusion Maximum tumor diameter and random GH concentration at diagnosis are the best predictors for remission after TSS in acromegaly.

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Commentary: “Prolactinomas: Prognostic Factors of Early Remission After Transsphenoidal Surgery”

Frontiers in Endocrinology ◽

10.3389/fendo.2021.695498 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lukas Andereggen ◽

Emanuel Christ

Keyword(s):

Prognostic Factors ◽

Transsphenoidal Surgery

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Transsphenoidal Surgery of Invasive Corticotroph Adenomas: Results in A Series of 86 Consecutive Patients

10.21203/rs.3.rs-810471/v1 ◽

2021 ◽

Author(s):

Congxin Dai ◽

Ming Feng ◽

Lin Lu ◽

Bowen Sun ◽

Yanghua Fan ◽

...

Keyword(s):

Transsphenoidal Surgery ◽

Remission Rate ◽

Partial Resection ◽

Gross Total Resection ◽

Subtotal Resection ◽

Total Resection ◽

Persistent Disease ◽

Biochemical Remission ◽

Corticotroph Adenomas

Abstract Objective: Surgery is first-line treatment for corticotroph adenomas. Although most of corticotroph adenomas are noninvasive microadenomas that show expansive growth to surrounding tissues, a small subset of them is locally invasive and difficult to manage. The aim of this study was to evaluate surgical outcome of invasive corticotroph adenomas from a single-center. Patients and Methods: The clinical features and outcomes of CD patients who underwent transsphenoidal surgery (TSS) between January 2000 and September 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinological, radiological, histopathological, surgical outcomes and a minimum 12-month follow-up of 86 consecutive CD patients with invasive corticotroph adenomas were retrospectively reviewed. Results: Eighty-six patients with invasive corticotroph adenomas were included in the study. The average age at TSS was 37.7 years (range, 12 to 67 years), with a female-to-male ratio of 3.1:1 (65/21). The median duration of symptoms was 52.6 months (range, 1.0 to 264 months). The average of maximum diameter of tumor was 17.6 mm (range, 4.5–70 mm). All 86 patients with invasive corticotroph adenomas were performed TSS by microscopic or endoscopic approach. Gross-total resection was achieved in 63 patients (73.3%), subtotal resection in 18 (20.9%), and partial resection in 5 (5.8%). After surgery, the overall postoperative immediate remission rate was 48.8% (42/86), 51.2 % (44/86) of patients maintained persistent hypercortisolism. In 42 patients with initial remission, 16.7 % (7/42) of them experienced a recurrence. In these patients with persistent disease and recurrent CD, data about further treatment was available for 30 patients. The radiotherapy was used for 15 patients, and 4 (26.7%) of them achieved biochemical remission. Repeat TSS was performed in 5 patients, and none achieved remission. Medication was administrated in 4 patients, and one of them obtained disease control. Adrenalectomy was performed in 6 patients, and 5 (83.3 %) achieved biochemical remission. At last follow-up, (33.3%) 10 of 30 patients were in remission, and 20 patients still had persistent disease. The remission rate in patients with invasive corticotroph adenomas who underwent gross-total resection and first TSS were significantly higher than that in patients undergoing subtotal resection, partial resection, and a second TSS (all P＜0.05). However, there was no significant difference in the remission rate between patient with different tumor size, Knosp Grade and surgical approaches (P＞0.05).Conclusion: The management of invasive corticotroph adenomas remain a therapeutic challenge due to incomplete resection of invasive and/or a large adenoma. With application of multiple techniques assistance, approximately half of the patients could achieve gross-total resection and biochemical remission via TSS by experienced neurosurgeons. The extent of tumor resection and number of operations were associated with surgical remission rate in invasive corticotroph adenomas. If the remission was not achieved by surgery, other treatments including radiotherapy, medical therapy, and even bilateral adrenalectomy are required.

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Long-term outcomes of transsphenoidal surgery for management of growth hormone–secreting adenomas: single-center results

Journal of Neurosurgery ◽

10.3171/2019.6.jns191187 ◽

2020 ◽

Vol 133 (5) ◽

pp. 1360-1370 ◽

Cited By ~ 2

Author(s):

Mohammed J. Asha ◽

Hirokazu Takami ◽

Carlos Velasquez ◽

Selfy Oswari ◽

Joao Paulo Almeida ◽

...

Keyword(s):

Growth Hormone ◽

Recurrence Rate ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Repeat Surgery ◽

Significant Difference ◽

Remission Rates ◽

Biochemical Remission

OBJECTIVETranssphenoidal surgery is advocated as the first-line management of growth hormone (GH)–secreting adenomas. Although disease control is defined by strict criteria for biochemical remission, the length of follow-up needed is not well defined in literature. In this report, the authors present their long-term remission rate and identify various predictive factors that might influence the clinical outcome.METHODSThe authors conducted a single-institute retrospective analysis of all transsphenoidal procedures for GH-secreting adenomas performed from January 2000 to June 2016. The primary outcome was defined as biochemical remission according to the 2010 consensus criteria and measured at the 1-year postoperative mark as well as on the last recorded follow-up appointment.Secondary variables included recurrence rate, patterns of clinical presentation, and outcome of adjuvant therapy (including repeat surgery). Subgroup analysis was performed for patients who had biochemical or radiological “discordance”—patients who achieved biochemical remission but with incongruent insulin-like growth factor 1 (IGF-1)/GH or residual tumor on MRI. Recurrence-free survival analysis was conducted for patients who achieved remission at 1 year after surgery.RESULTSEighty-one patients (45 female and 36 male) with confirmed acromegaly treated with transsphenoidal surgery were included. In 62 cases the patients were treated with a pure endoscopic approach and in 19 cases an endoscopically assisted microscopic approach was used.Primary biochemical remission after surgery was achieved in 59 cases (73%) at 1 year after surgery. However, only 41 patients (51%) remained in primary surgical remission (without any adjuvant treatment) at their last follow-up appointment, indicating a recurrence rate of 31% (18 of 59 patients) over the duration of follow-up (mean 100 ± 61 months). Long-term remission rates for pure endoscopic and endoscopically assisted cases were not significantly different (48% vs 52%, p = 0.6). Similarly, no significant difference in long-term remission was detected between primary surgery and repeat surgery (54% vs 33%, p = 0.22).Long-term remission was significantly influenced by extent of resection, cavernous sinus invasion (radiologically as well as surgically reported), and preoperative and early postoperative GH and IGF-1 levels (within 24–48 hours after surgery) as well as by clinical grade, with lower remission rates in patients with dysmorphic features and/or medical comorbidities (grade 2–3) compared to minimally symptomatic or silent cases (grade 1).CONCLUSIONSThe long-term surgical remission rate appears to be significantly less than “early” remission rates and is highly dependent on the extent of tumor resection. The authors advocate a long-term follow-up regimen and propose a clinical grading system that may aid in predicting long-term outcome in addition to the previously reported anatomical factors. The role of repeat surgery is highlighted.

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Factors Associated with Biochemical Remission after Microscopic Transsphenoidal Surgery for Acromegaly

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0033-1354578 ◽

2013 ◽

Vol 75 (01) ◽

pp. 047-052 ◽

Cited By ~ 25

Author(s):

Hai Sun ◽

Jessica Brzana ◽

Chris Yedinak ◽

Sakir Gultekin ◽

Johnny Delashaw ◽

...

Keyword(s):

Transsphenoidal Surgery ◽

Factors Associated ◽

Biochemical Remission

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Long-term endocrinological follow-up evaluation in 115 patients who underwent transsphenoidal surgery for acromegaly

Journal of Neurosurgery ◽

10.3171/jns.1998.89.3.0353 ◽

1998 ◽

Vol 89 (3) ◽

pp. 353-358 ◽

Cited By ~ 165

Author(s):

Pamela U. Freda ◽

Sharon L. Wardlaw ◽

Kalmon D. Post

Keyword(s):

Transsphenoidal Surgery ◽

Remission Rate ◽

Postoperative Radiotherapy ◽

Term Outcome ◽

Long Term Outcome ◽

Content Type ◽

Biochemical Remission ◽

Fine Print

Object. The results of surgical therapy for acromegaly were assessed using carefully conducted endocrinological testing in 115 patients who underwent transsphenoidal surgery from 1981 to 1995. Methods. Ninety-nine of the 115 patients could be contacted for follow-up review; in 57 of the patients an endocrinological assessment was performed by the authors. Biochemical cure was strictly defined as a normalization of the insulin-like growth factor(IGF)—I level (obtained in 100 patients) and/or a basal or glucose-suppressed growth hormone (GH) level of 2 ng/ml or less. The mean length of follow up from transsphenoidal surgery to laboratory testing was 5.4 years with a maximum of 15.7 years. After transsphenoidal surgery alone, 61% of the patients achieved a biochemical remission; the remission rate was 88% for patients with microadenomas and 53% for those with macroadenomas. Tumor size and preoperative GH level tended to correlate negatively with outcome of surgery. Early postoperative GH level tended to correlate with long-term outcome; in cases in which the early postoperative GH level was lower than 3 ng/ml, the chance of long-term remission was 89%. Thirty-two patients received postoperative radiotherapy: in 10 (31%) of these patients the disease is currently in remission after surgery and radiotherapy only and in three others the disease is in remission with the addition of medical therapy. The overall complication rate was 6.9% with no cerebrospinal fluid leaks, meningitis, permanent diabetes insipidus, or new hypopituitarism. The overall recurrence rate was low at 5.4%. Conclusions. This series shows, based on IFGF—I measurements and strict GH supression criteria to define remission, that transsphenoidal surgery provides an excellent chance for long-term cure in patients with microadenomas. Surgery alone is successful in most patients with noninvasive macroadenomas; however, most patients with invasive macroadenomas will require adjunctive therapy. Recurrences are uncommon when biochemical remission is clearly documented postoperatively.

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