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Tyler Cardinal, Martin J. Rutkowski, Alexander Micko, Mark Shiroishi, Chia-Shang Jason Liu, Bozena Wrobel, John Carmichael and Gabriel Zada

OBJECTIVE

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor–1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation.

METHODS

The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values.

RESULTS

The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves.

CONCLUSIONS

Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

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Meng Law, Regina Wang, Chia-Shang J. Liu, Mark S. Shiroishi, John D. Carmichael, William J. Mack, Martin Weiss, Danny J. J. Wang, Arthur W. Toga and Gabriel Zada

Cushing’s disease is caused by adrenocorticotrophic hormone (ACTH)–secreting pituitary adenomas, which are often difficult to identify on standard 1.5-T or 3-T MRI, including dynamic contrast imaging. Inferior petrosal and cavernous sinus sampling remains the gold standard for MRI-negative Cushing’s disease.

The authors report on a 27-year-old woman with Cushing’s disease in whom the results of standard 1.5-T and 3-T MRI, including 1.5-T dynamic contrast imaging, were negative. Inferior petrosal sinus sampling showed a high central-to-peripheral ACTH ratio (148:1) as well as a right-to-left ACTH gradient (19:1), suggesting a right-sided pituitary microadenoma. The patient underwent 7-T MRI, which showed evidence of a right-sided pituitary lesion with focal hypoenhancement not visualized on 1.5-T or 3-T MRI. The patient underwent an endoscopic endonasal transsphenoidal operation, with resection of a right-sided pituitary mass. Postoperatively, she developed clinical symptoms suggestive of adrenal insufficiency and a nadir cortisol level of 1.6 μg/dl on postoperative day 3, and hydrocortisone therapy was initiated. Permanent histopathology specimens showed Crooke’s hyaline change and ACTH-positive cells suggestive of an adenoma.

MRI at 7 T may be beneficial in identifying pituitary microadenoma location in cases of standard 1.5-T and 3-T MRI-negative Cushing’s disease. In the future, 7-T MRI may preempt inferior petrosal sinus sampling and help in cases of standard and dynamic contrast 1.5-T and 3-T MRI-negative Cushing’s disease.

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Martin J. Rutkowski, Ki-Eun Chang, Tyler Cardinal, Robin Du, Ali R. Tafreshi, Daniel A. Donoho, Andrew Brunswick, Alexander Micko, Chia-Shang J. Liu, Mark S. Shiroishi, John D. Carmichael and Gabriel Zada

OBJECTIVE

Pituitary adenoma (PA) consistency, or texture, is an important intraoperative characteristic that may dictate operative dissection techniques and/or instruments used for tumor removal during endoscopic endonasal approaches (EEAs). The impact of PA consistency on surgical outcomes has yet to be elucidated.

METHODS

The authors developed an objective 5-point grading scale for PA consistency based on intraoperative characteristics, including ease of tumor debulking, manipulation, and instrument selection, ranging from cystic/hemorrhagic tumors (grade 1) to calcified tumors (grade 5). The proposed grading system was prospectively assessed in 306 consecutive patients who underwent an EEA for PAs, and who were subsequently analyzed for associations with surgical outcomes, including extent of resection (EOR) and complication profiles.

RESULTS

Institutional database review identified 306 patients who underwent intraoperative assessment of PA consistency, of which 96% were macroadenomas, 70% had suprasellar extension, and 44% had cavernous sinus invasion (CSI). There were 214 (69.9%) nonfunctional PAs and 92 functional PAs (31.1%). Distribution of scores included 15 grade 1 tumors (4.9%), 112 grade 2 tumors (36.6%), 125 grade 3 tumors (40.8%), 52 grade 4 tumors (17%), and 2 grade 5 tumors (0.7%). Compared to grade 1/2 and grade 3 PAs, grade 4/5 PAs were significantly larger (22.5 vs 26.6 vs 27.4 mm, p < 0.01), more likely to exhibit CSI (39% vs 42% vs 59%, p < 0.05), and trended toward nonfunctionality (67% vs 68% vs 82%, p = 0.086). Although there was no association between PA consistency and preoperative headaches or visual dysfunction, grade 4/5 PAs trended toward preoperative (p = 0.058) and postoperative panhypopituitarism (p = 0.066). Patients with preoperative visual dysfunction experienced greater improvement if they had a grade 1/2 PA (p < 0.05). Intraoperative CSF leaks were noted in 32% of cases and were more common with higher-consistency-grade tumors (p = 0.048), although this difference did not translate to postoperative CSF leaks. Gross-total resection (%) was more likely with lower PA consistency score as follows: grade 1/2 (60%), grade 3 (50%), grade 4/5 (44%; p = 0.045). Extracapsular techniques were almost exclusively performed in grade 4/5 PAs. Assignment of scores showed low variance and high reproducibility, with an intraclass correlation coefficient of 0.905 (95% CI 0.815–0.958), indicating excellent interrater reliability.

CONCLUSIONS

These findings demonstrate clinical validity of the proposed intraoperative grading scale with respect to PA subtype, neuroimaging features, EOR, and endocrine complications. Future studies will assess the relation of PA consistency to preoperative MRI findings to accurately predict consistency, thereby allowing the surgeon to tailor the exposure and prepare for varying resection strategies.

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Janelle Cyprich, Dhiraj J. Pangal, Martin Rutkowski, Daniel A. Donoho, Mark Shiroishi, Chia-Shang Jason Liu, John D. Carmichael and Gabriel Zada

OBJECTIVE

Sociodemographic disparities in health outcomes are well documented, but the effects of such disparities on preoperative presentation of pituitary adenomas (PA) and surgical outcomes following resection are not completely understood. In this study the authors sought to compare the preoperative clinical characteristics and postoperative outcomes in patients undergoing PA resection at a private hospital (PH) versus a safety-net hospital (SNH).

METHODS

The authors conducted a retrospective review over a 36-month period of patients with PAs who underwent endoscopic endonasal transsphenoidal surgery performed by the same attending neurosurgeon at either a PH or an SNH at a single academic medical institution.

RESULTS

A total of 92 PH patients and 69 SNH patients were included. SNH patients were more likely to be uninsured or have Medicaid (88.4% vs 10.9%, p < 0.0001). A larger percentage of SNH patients were Hispanic (98.7% vs 32.6% p < 0.0001), while PH patients were more likely to be non-Hispanic white (39.1% vs 4.3%, p < 0.0001). SNH patients had a larger mean PA diameter (26.2 vs 22.4 mm, p = 0.0347) and a higher rate of bilateral cavernous sinus invasion (13% vs 4.3%, p = 0.0451). SNH patients were more likely to present with headache (68.1% vs 45.7%, p = 0.0048), vision loss (63.8% vs 35.9%, p < 0.0005), panhypopituitarism (18.8% vs 4.3%, p = 0.0031), and pituitary apoplexy (18.8% vs 7.6%, p = 0.0334). Compared to PH patients, SNH patients were as likely to undergo gross-total resection (73.9% vs 76.1%, p = 0.7499) and had similar rates of postoperative improvement in headache (80% vs 89%, p = 0.14) and vision (82% vs 84%, p = 0.74), but had higher rates of postoperative panhypopituitarism (23% vs 10%, p = 0.04) driven by preoperative endocrinopathies. Although there were no differences in tumor recurrence or progression, loss to follow-up was seen in 7.6% of PH versus 18.6% (p = 0.04) of SNH patients.

CONCLUSIONS

Patients presenting to the SNH were more often uninsured or on Medicaid and presented with larger, more advanced pituitary tumors. SNH patients were more likely to present with headaches, vision loss, and apoplexy, likely translating to greater improvements in headache and vision observed after surgery. These findings highlight the association between medically underserved populations and more advanced disease states at presentation, and underscore the likely role of academic tertiary multidisciplinary care teams and endoscopic PA resection in somewhat mitigating sociodemographic factors known to portend poorer outcomes, though longer-term follow-up is needed to confirm these findings.