A novel noninstrumented surgical approach for foramen reconstruction for isthmic spondylolisthesis in patients with radiculopathy: preliminary clinical and radiographic outcomes.

OBJECTIVE The health care costs for instrumented spine surgery have increased dramatically in the last few decades. The authors present a novel noninstrumented surgical approach for patients with isthmic spondylolisthesis, with clinical and radiographic results. METHODS Charts of patients who underwent this technique were reviewed. The procedure consisted of nerve root decompression by reconstruction of the intervertebral foramen. This was achieved by removal of the pedicle followed by noninstrumented posterolateral fusion in which autologous bone graft from the right iliac crest was used. Outcomes regarding radicular complaints, bony fusion, progression of the slip, and complications were evaluated using patient history and radiographs obtained at follow-up intervals of 3-18 months after surgery. RESULTS A total of 58 patients with a mean age of 47 years were treated with this method. Partial removal of the pedicle was performed in 93.1% of the cases, whereas in 6.9% of the cases the entire pedicle was removed. The mean duration of surgery was 216.5 ± 54.5 minutes (range 91-340 minutes). The mean (± SD) duration of hospitalization was 10.1 ± 2.9 days (range 5-18 days). After 3 months of follow-up, 86% of the patients reported no leg pain, and this dropped to 81% at last follow-up. Radiographic follow-up showed bony fusion in 87.7% of the patients. At 1 year, 5 patients showed progression of the slip, which in 1 patient prompted a second operation within 1 year. No major complications occurred. CONCLUSIONS Treatment of isthmic spondylolisthesis by reconstruction of the intervertebral neuroforamen and posterolateral fusion in situ is a safe procedure and has comparable results with the existing techniques. Cost-effectiveness research comparing this technique to conventional instrumented fusion techniques is necessary to evaluate the merits for both patients and society.

Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant.

BACKGROUND: Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown. AIM OF THE STUDY: To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression. MATERIALS AND METHODS: At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry. RESULTS: Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024). CONCLUSION: In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.

Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study).

Aim: To assess the efficacy and safety of pasireotide long-acting release (PAS-LAR) alone or in combination with pegvisomant by switching patients with acromegaly who were well controlled with long-acting somatostatin analogues (LA-SSAs) and pegvisomant to PAS-LAR with or without pegvisomant. Methods: Sixty-one patients with acromegaly were enrolled in a prospective open-label study. We included patients with an insulin-like growth factor I (IGF-I) ≤1.2 × upper limit of normal (ULN) during treatment with LA-SSAs and pegvisomant. At baseline, the pegvisomant dose was reduced by 50% up to 12 weeks. When IGF-I remained ≤1.2 × ULN after 12 weeks, patients were switched to PAS-LAR 60 mg monotherapy. When IGF-I was >1.2 × ULN, patients were switched to PAS-LAR 60 mg, and they continued with the 50% reduced pegvisomant dose. Results: At baseline, mean IGF-I was 0.97 × ULN, and the median pegvisomant dose was 80 mg/wk. At 12 weeks, mean IGF-I increased to 1.59 × ULN, and IGF-I levels ≤1.2 ULN were observed in 24.6% of participants. At 24 weeks, IGF-I levels were reduced into the reference range in 73.8% of patients. Between baseline and 24 weeks, the pegvisomant dose was reduced by 66.1%. PAS-LAR was well tolerated, but hyperglycemia was the most frequent adverse event. The frequency of diabetes increased from 32.8% at baseline to 68.9% at 24 weeks. Conclusions: Switching to PAS-LAR, either as monotherapy or combination with pegvisomant, can control IGF-I levels in most patients. PAS-LAR demonstrated a pegvisomant-sparing effect of 66% compared with the combination with LA-SSAs. Hyperglycemia was the most important safety issue.

Efficacy and Safety of switching to Pasireotide in Acromegaly Patients controlled with Pegvisomant and Somatostatin Analogues: PAPE extension study.

OBJECTIVE: to assess the efficacy and safety after 48 weeks of treatment with pasireotide long-acting-release (PAS-LAR) alone or in combination with pegvisomant in patients with acromegaly. In addition, we assessed the relation between insulin secretion and pasireotide-induced hyperglycemia. DESIGN: The PAPE extension study is a prospective follow-up study until 48 weeks after the core study of 24 weeks. METHODS: 59 out of 61 patients entered the extension study. Efficacy was defined as the percentage of patients achieving IGF-I normalization (≤ 1.2 x the Upper Limit of Normal (ULN)) at 48-weeks through protocol-based adjustment of pegvisomant and PAS-LAR doses. At baseline, insulin secretion was assessed by an oral glucose tolerance test (OGTT). RESULTS: At the end of the study median IGF-I was 0.98 x ULN, and 77% of patients achieved normal IGF-I levels with a mean pegvisomant dose of 64 mg/week, and an overall cumulative pegvisomant dose reduction of 52%. Frequency of diabetes mellitus increased from 68% at 24 weeks to 77% at 48 weeks, and 9 patients discontinued PAS-LAR treatment, mainly because of severe hyperglycemia. Pasireotide-induced hyperglycemia was inversely correlated with baseline insulin secretion (r = -0.37, P < 0.005). CONCLUSIONS: PAS-LAR normalizes IGF-I levels in most acromegaly patients, with a fifty percent pegvisomant-sparing effect. However, PAS-LAR treatment coincided with a high incidence of diabetes mellitus. The risk for developing diabetes during PAS-LAR treatment seems inversely related to insulin secretion at baseline.

Very long-term sequelae of craniopharyngioma.

OBJECTIVE: Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. DESIGN: Cross-sectional study based on retrospective data. METHODS: We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection (n = 25), subtotal resection without radiotherapy (n = 44), subtotal resection with radiotherapy (n = 25), cyst aspiration without radiotherapy (n = 8), and 90Yttrium brachytherapy (n = 21). RESULTS: Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. CONCLUSIONS: Long-term health conditions were comparable after different initial craniopharyngioma treatment approaches and were generally more frequent in patients with childhood- compared with adult-onset disease.