Comparison of 68Ga DOTATATE to 18F-FDG Uptake Is Useful in the Differentiation of Residual or Recurrent Pituitary Adenoma From the Remaining Pituitary Tissue After Transsphenoidal Adenomectomy
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Abstract:
The evaluation of the remaining pituitary tissue and recurrent or residual tumor after the pituitary adenoma resection is difficult. However, it is essential to assess the size of the recurrent tumor and remaining pituitary reserve before resurgery. This study aimed to distinguish the remaining pituitary tissue from pituitary adenoma with Ga 1,4,7,10-tetraazacyclododecane-N,N',N″,N″'-tetraacetic acid-D-Phe,Tyr3-octreotate (DOTATATE) and F-FDG PET imaging in patients status post transsphenoidal adenomectomy.Thirty-five patients with suspected recurrent/residual pituitary tumors were retrospectively evaluated. All of these patients underwent DOTATATE and FDG PET/CT within 1 week before additional surgery. The DOTATATE and FDG uptake levels were compared. The image findings were then compared with pathology results after the additional surgery.Residual or recurrent pituitary adenoma were confirmed pathologically in all 35 patients. One recurrent pituitary adenoma did not have either DOTATATE or FDG uptake. In the remaining 34 adenomas, 33 had higher FDG uptake than DOTATATE uptake. In comparison, DOTATATE had significant higher uptake than FDG in the remaining pituitary tissues in all cases.Different degree of uptake of Ga DOTATATE and F-FDG PET/CT in the remaining pituitary tissue and recurrent/residual pituitary tumor indicated that combined analysis of Ga DOTATATE and F-FDG PET/CT might be of clinical value in differentiating recurrent/residual pituitary adenoma from the remaining pituitary tissue.Keywords:
Transsphenoidal surgery
Pituitary Tumors
Pituitary Tumors
Pituitary neoplasm
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OBJECTIVE Pituitary adenomas account for approximately 10% of intracranial tumors and have an estimated prevalence of 15%–20% in the general US population. Resection is the primary treatment for pituitary adenomas, and the transsphenoidal approach remains the most common. The greatest challenge with pituitary adenomas is that 20% of patients develop tumor recurrence. Current approaches to reduce recurrence, such as intraoperative MRI, are costly, associated with high false-positive rates, and not recommended. Pituitary adenomas are known to overexpress folate receptor alpha (FRα), and it was hypothesized that OTL38, a folate analog conjugated to a near-infrared (NIR) fluorescent dye, could provide real-time intraoperative visual contrast of the tumor versus the surrounding nonneoplastic tissues. The preliminary results of this novel clinical trial are presented. METHODS Nineteen adult patients who presented with pituitary adenoma were enrolled. Patients were infused with OTL38 2–4 hours prior to surgery. A 4-mm endoscope with both visible and NIR light capabilities was used to visualize the pituitary adenoma and its margins in real time during surgery. The signal-to-background ratio (SBR) was recorded for each tumor and surrounding tissues at various endoscope-to-sella distances. Immunohistochemical analysis was performed to assess the FRα expression levels in all specimens and classify patients as having either high or low FRα expression. RESULTS Data from 15 patients (4 with null cell adenomas, 1 clinically silent gonadotroph, 1 totally silent somatotroph, 5 with a corticotroph, 3 with somatotrophs, and 1 somatocorticotroph) were analyzed in this preliminary analysis. Four patients were excluded for technical considerations. Intraoperative NIR imaging delineated the main tumors in all 15 patients with an average SBR of 1.9 ± 0.70. The FRα expression level of the adenomas and endoscope-to-sella distance had statistically significant impacts on the fluorescent SBRs. Additional considerations included adenoma functional status and time from OTL38 injection. SBRs were 3.0 ± 0.29 for tumors with high FRα expression (n = 3) and 1.6 ± 0.43 for tumors with low FRα expression (n = 12; p < 0.05). In 3 patients with immunohistochemistry-confirmed FRα overexpression (2 patients with null cell adenoma and 1 patient with clinically silent gonadotroph), intraoperative NIR imaging demonstrated perfect classification of the tumor margins with 100% sensitivity and 100% specificity. In addition, for these 3 patients, intraoperative residual fluorescence predicted postoperative MRI results with perfect concordance. CONCLUSIONS Pituitary adenomas and their margins can be intraoperatively visualized with the preoperative injection of OTL38, a folate analog conjugated to NIR dye. Tumor-to-background contrast is most pronounced in adenomas that overexpress FRα. Intraoperative SBR at the appropriate endoscope-to-sella distance can predict adenoma FRα expression status in real time. This work suggests that for adenomas with high FRα expression, it may be possible to identify margins and to predict postoperative MRI findings.
Transsphenoidal surgery
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Pituitary Tumors
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Adenoma of the pituitary gland represents one of the commonest spontaneous tumors in strains of laboratory rats. In a retrospective survey of pituitary glands from 2165 albino Wistar rats, the total number of pituitary adenomas was 501, representing an overall incidence of 23% with females showing a higher incidence (32%) than males (13%). Pituitary adenoma was rare from 6-52 weeks of age and accounted for only 0.2% of the total incidence. The first pituitary tumors in this series were observed at 32 weeks in 2 female rats and at 40 weeks in a male rat. From 52-85 weeks of age, incidence remained low, and then increased progressively in animals that died from 85-110 weeks of age. In a series of 200 Wistar rats, detailed evaluation was completed for neoplastic and hyperplastic lesions of the pituitary gland. The immunocytochemical characteristics of the pituitary adenoma were investigated using markers for prolactin, growth hormone, and thyrotropic hormone. Positive immunoperoxidase staining revealed an incidence of 59% prolactinomas in both male and female rats. Forty-one percent of pituitary adenomas did not stain for prolactin, thyrotropic, or growth hormone and showed no specific morphologic differences from prolactinomas. The application of immunoperoxidase-staining techniques offers a useful tool for characterizing secretory activity of pituitary adenomas and evaluating histopathologic changes of the pituitary gland.
Immunoperoxidase
Pituitary Tumors
Pituitary neoplasm
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Transsphenoidal surgery
Gold standard (test)
Pituitary Tumors
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In 48 patients undergoing transsphenoidal surgery for pituitary adenoma, the intrasellar pressure was recorded during surgery. In 14 patients, adenoma blood flow was measured with the technique of local injection of 133xenon. Median intrasellar pressure was 30 mmHg (range 8-62), n = 48, and median adenoma blood flow was 8 ml/100 g/min (range 0-37), n = 14. In two patients, blood flow in the anterior pituitary gland was measured, and values of 26 and 22 ml/100 g/min were obtained. The finding that intrasellar pressure is above central venous and intracranial pressure suggests the possibility that the adenoma and the anterior pituitary gland are supplied not only with venous blood, but receive an additional arterial supply at a less than normal arterial pressure. In three cases perfusion pressures that caused arrest of adenoma blood flow were found, and these observations are discussed with reference to pituitary apoplexy.
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Pituitary apoplexy
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Fluid-attenuated inversion recovery
Cushing Disease
Hypercortisolemia
Cushing's disease
Pituitary Tumors
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Objective
To compare the effect of microscopic pituitary adenoma resection and neuroendoscopic transsphenoidal approach surgery for pituitary adenoma resection.
Methods
Eighty-four patients with pituitary adenoma admitted to Changzhi People’s Hospital from March 2010 to March 2019 were selected as the study subjects and grouped according to the parity of admission sequence. They were divided into the control group (42 cases, pituitary adenoma resection under microscope) and the observation group (42 cases, neuroendoscopic nasal transsphenoidal approach of pituitary adenoma resection). The operation condition, growth hormone levels, serum stress index and complications were compared between the two groups.
Results
The duration of operation and hospitalization in the observation group were significantly shorter than those in the control group(P<0.05), while the intraoperative bleeding volume, adrenocorticotropic hormone , growth hormone, prolactin , cortisol and norepinephrine levels 3 days after operation in the observation group were lower than those in the control group(P<0.05). The incidence of complications in the observation group (4.76%) was significantly lower than that in the control group (23.81%), and the differences were statistically significant(P<0.05).
Conclusions
Neuroendoscopic transsphenoidal surgery for pituitary adenoma can effectively shorten the treatment time, reduce the stress response and incidence of complications.
Key words:
Endoscopic transsphenoidal approach; Pituitary adenoma; Serum stress response; Complication
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Pituitary Tumors
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Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.
Pituitary Tumors
Pituitary neoplasm
Posterior pituitary
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Transsphenoidal surgery is an established treatment for pituitary adenomas. We examined outcomes and time points following transsphenoidal surgery for pituitary adenoma to identify reporting heterogeneity within the literature.
Transsphenoidal surgery
Human physiology
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Objectives: Invasiveness is the feature of malignant tumor,which some pituitary adenomas have.The DNA ploidy and the proliferation ability of invasive adenoma cells were studied. Methods: Pituitary adenoma cells were assayed by Flow Cytometer and Image Cytometer. Results: Invasiveness of pituitary adenoma correlated with the proportion of abnormal DNA ploidy cells. Conclusions: From the DNA ploidy of invasive pituitary adenoma,we could conclude that invasive pituitary adenoma developed malignantly.
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Pituitary neoplasm
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