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Ariane Lewis, Amol Raheja and Ian E. McCutcheon

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Stephen J. Hentschel and Ian E. McCutcheon

The most common cause of Cushing syndrome is Cushing disease, in which hypercortisolism is produced by a functional adrenocorticotropic hormone–producing adenoma of the anterior pituitary gland. The common therapies available include microsurgical resection, conventional fractionated radiotherapy, and stereotactic radiosurgery (SRS). In this article the authors review the indications, results, and complications associated with SRS in the treatment of Cushing disease.

In as many as 90% of patients SRS results in disease remission, which is defined as a normal 24-hour urinary free cortisol level and a normal or subnormal morning serum cortisol level. Although in most patients who are subsequently cured a marked decrease in the serum cortisol level is demonstrated within 3 months after treatment, a biochemical cure may be delayed up to 3 years in some cases. Complications following SRS for pituitary adenomas are uncommon, particularly in patients with microadenomas, which are most commonly seen in Cushing disease. The most common complication is hypopituitarism, which occurs in up to 50% of patients with a mean latency period of 5 years. Radiation-induced optic neuropathy has been reported in less than 2% of cases and induction of a secondary neoplasm in less than 1% of cases.

For patients with Cushing disease, the rate of endocrinological cure following SRS appears to be similar to that attained using microsurgical resection. In contrast to surgery, SRS has the benefit of being noninvasive and associated with a very low incidence of diabetes insipidus, although hypopituitarism may be more common with SRS. With continued follow-up patient reviews and additional experience with SRS, it may become possible to make more definitive statements regarding SRS as the initial treatment for patients with Cushing disease.

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Julie E. York, Garrett L. Walsh, Frederick F. Lang, Joe B. Putnam, Ian E. McCutcheon, Stephen G. Swisher, Ritsuko Komaki and Ziya L Gokaslan

Traditionally, superior sulcus tumors of the lung that involve the chest wall and spinal column have been considered to be unresectable, and historically, patients harboring these tumors have been treated with local radiation therapy with, at best, modest results. The value of gross-total resection remains unclear in this patient population; however, with the recent advances in surgical technique and spinal instrumentation, procedures involving more radical removal of such tumors are now possible. At The University of Texas M. D. Anderson Cancer Center, the authors have developed a new technique for resecting superior sulcus tumors that invade the chest wall and spinal column. They present a technical description of this procedure and results in nine patients in whom stage IIIb superior sulcus tumors extensively invaded the vertebral column. These patients underwent gross-total tumor resection via a combined approach that included posterolateral thoracotomy, apical lobectomy, chest wall resection, laminectomy, vertebrectomy, anterior spinal column reconstruction with methylmethacrylate, and placement of spinal instrumentation. There were six men and three women, with a mean age of 55 years (range 36–72 years). Histological examination revealed squamous cell carcinoma (three patients), adenocarcinoma (four patients), and large cell carcinoma (two patients). The mean postoperative follow-up period was 16 months. All patients are currently ambulatory or remained ambulatory until they died. Pain related to tumor invasion improved in four patients and remained unchanged in five. In three patients instrumentation failed and required revision. There was one case of cerebrospinal leak that was treated with lumbar drainage and one case of wound breakdown that required revision. Two patients experienced local tumor recurrence, and one patient developed a second primary lung tumor. The authors conclude that in selected patients, combined radical resection of superior sulcus tumors of the lung that involve the chest wall and spinal column may represent an acceptable treatment modality that can offer a potential cure while preserving neurological function and providing pain control.

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Scott L. Zuckerman, Ganesh Rao, Laurence D. Rhines, Ian E. McCutcheon, Richard G. Everson and Claudio E. Tatsui

OBJECTIVE

Treatment of epidural spinal cord compression (ESCC) caused by tumor includes surgical decompression and stabilization followed by postoperative radiation. In the case of severe axial loading impairment, anterior column reconstruction is indicated. The authors describe the use of interbody distraction to restore vertebral body height and correct kyphotic angulation prior to reconstruction with polymethylmethacrylate (PMMA), and report the long-term durability of such reconstruction.

METHODS

A single institution, prospective series of patients with ESCC undergoing single-stage decompression, anterior column reconstruction, and posterior instrumentation from 2013 to 2016 was retrospectively analyzed. Several demographic, perioperative, and radiographic measurements were collected. Descriptive statistics were compiled, in addition to postoperative changes in anterior height, posterior height, and kyphosis. Paired Student t-tests were performed for each variable. Overall survival was calculated using the techniques described by Kaplan and Meier.

RESULTS

Twenty-one patients underwent single-stage posterior decompression with interbody distraction and anterior column reconstruction using PMMA. The median age and Karnofsky Performance Scale score were 61 years and 70, respectively. Primary tumors included renal cell (n = 8), lung (n = 4), multiple myeloma (n = 2), prostate (n = 2), and other (n = 5). Eighteen patients underwent a single-level vertebral body reconstruction and 3 underwent multilevel transpedicular corpectomies. The median survival duration was 13.3 months. In the immediate postoperative setting, statistically significant improvement was noted in anterior body height (p = 0.0017, 95% confidence interval [CI] −4.15 to −1.11) and posterior body height (p = 0.0116, 95% CI −3.14 to −0.45) in all patients, and improved kyphosis was observed in those with oblique endplates (p = 0.0002, 95% CI 11.16–20.27). In the median follow-up duration of 13.9 months, the authors observed 3 cases of asymptomatic PMMA subsidence. One patient required reoperation in the form of extension of fusion.

CONCLUSIONS

In situ interbody distraction allows safe and durable reconstruction with PMMA, restores vertebral height, and corrects kyphotic deformities associated with severe pathological fractures caused by tumor. This is accomplished with minimal manipulation of the thecal sac and avoiding an extensive 360° surgical approach in patients who cannot tolerate extensive surgery.

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Sherise D. Ferguson, Nicholas B. Levine, Dima Suki, Andrew J. Tsung, Fredrick F. Lang, Raymond Sawaya, Jeffrey S. Weinberg and Ian E. McCutcheon

OBJECTIVE

Fourth ventricle tumors are rare, and surgical series are typically small, comprising a single pathology, or focused exclusively on pediatric populations. This study investigated surgical outcome and complications following fourth ventricle tumor resection in a diverse patient population. This is the largest cohort of fourth ventricle tumors described in the literature to date.

METHODS

This is an 18-year (1993–2010) retrospective review of 55 cases involving patients undergoing surgery for tumors of the fourth ventricle. Data included patient demographic characteristics, pathological and radiographic tumor characteristics, and surgical factors (approach, surgical adjuncts, extent of resection, etc.). The neurological and medical complications following resection were collected and outcomes at 30 days, 90 days, 6 months, and 1 year were reviewed to determine patient recovery. Patient, tumor, and surgical factors were analyzed to determine factors associated with the frequently encountered postoperative neurological complications.

RESULTS

There were no postoperative deaths. Gross-total resection was achieved in 75% of cases. Forty-five percent of patients experienced at least 1 major neurological complication, while 31% had minor complications only. New or worsening gait/focal motor disturbance (56%), speech/swallowing deficits (38%), and cranial nerve deficits (31%) were the most common neurological deficits in the immediate postoperative period. Of these, cranial nerve deficits were the least likely to resolve at follow-up. Multivariate analysis showed that patients undergoing a transvermian approach had a higher incidence of postoperative cranial nerve deficits, gait disturbance, and speech/swallowing deficits than those treated with a telovelar approach. The use of surgical adjuncts (intraoperative navigation, neurophysiological monitoring) did not significantly affect neurological outcome. Twenty-two percent of patients required postoperative CSF diversion following tumor resection. Patients who required intraoperative ventriculostomy, those undergoing a transvermian approach, and pediatric patients (< 18 years old) were all more likely to require postoperative CSF diversion. Twenty percent of patients suffered at least 1 medical complication following tumor resection. Most complications were respiratory, with the most common being postoperative respiratory failure (14%), followed by pneumonia (13%).

CONCLUSIONS

The occurrence of complications after fourth ventricle tumor surgery is not rare. Postoperative neurological sequelae were frequent, but a substantial number of patients had neurological improvement at long-term followup. Of the neurological complications analyzed, postoperative cranial nerve deficits were the least likely to completely resolve at follow-up. Of all the patient, tumor, and surgical variables included in the analysis, surgical approach had the most significant impact on neurological morbidity, with the telovelar approach being associated with less morbidity.

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Ziya L. Gokaslan, Julie E. York, Garrett L. Walsh, Ian E. McCutcheon, Frederick F. Lang, Joe B. Putnam Jr., David M. Wildrick, Stephen G. Swisher, Dima Abi-Said and Raymond Sawaya

Anterior approaches to the spine for the treatment of spinal tumors have gained acceptance; however, in most published reports, patients with primary, metastatic, or chest wall tumors involving cervical, thoracic, or lumbar regions of the spine are combined. The purpose of this study was to provide a clear perspective of results that can be expected in patients who undergo anterior vertebral body resection, reconstruction, and stabilization for spinal metastases that are limited to the thoracic region.

Outcome is presented for 72 patients with metastatic spinal tumors who were treated by transthoracic vertebrectomy at The University of Texas M. D. Anderson Cancer Center. The predominant primary tumors included renal cancer in 19 patients, breast cancer in 10, melanoma or sarcoma in 10, and lung cancer in nine patients. The most common presenting symptoms were back pain, which occurred in 90% of patients, and lower-extremity weakness, which occurred in 64% of patients. All patients underwent transthoracic vertebrectomy, decompression, reconstruction with methylmethacrylate, and anterior fixation with locking plate and screw constructs. Supplemental posterior instrumentation was required in seven patients with disease involving the cervicothoracic or thoracolumbar junction, which was causing severe kyphosis. After surgery, pain improved in 60 of 65 patients. This improvement was found to be statistically significant (p < 0.001) based on visual analog scales and narcotic analgesic medication use. Thirty-five of the 46 patients who presented with neurological dysfunction improved significantly (p < 0.001) following the procedure. Thirty-three patients had weakness but could ambulate preoperatively. Seventeen of these 33 regained normal strength, 15 patients continued to have weakness, and one patient was neurologically worse postoperatively. Of the 13 preoperatively nonambulatory patients, 10 could walk after surgery and three were still unable to walk but showed improved motor function. Twenty-one patients had complications ranging from minor atelectasis to pulmonary embolism. The 30-day mortality rate was 3%. The 1-year survival rate for the entire study population was 62%.

These results suggest that transthoracic vertebrectomy and spinal stabilization can improve the quality of life considerably in cancer patients with spinal metastasis by restoring or preserving ambulation and by controlling intractable spinal pain with acceptable rates of morbidity and mortality.

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Claudio E. Tatsui, Dima Suki, Ganesh Rao, Stefan S. Kim, Abhijit Salaskar, Mustafa Aziz Hatiboglu, Ziya L. Gokaslan, Ian E. McCutcheon and Laurence D. Rhines

Object

Renal cell carcinoma (RCC) frequently metastasizes to the spine, and the prognosis can be quite variable. Surgical removal of the tumor with spinal reconstruction has been a mainstay of palliative treatment. The ability to predict prognosis is valuable when determining the role and magnitude of surgical intervention in cancer patients. To better identify factors affecting survival in patients undergoing surgery for spinal metastasis from RCC, the authors undertook a retrospective analysis of a large patient cohort at a tertiary care cancer center.

Methods

Relevant clinical data on a consecutive series of patients who had undergone surgery for spinal metastasis of RCC between 1993 and 2007 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Demographic data, histopathological grade of primary tumor, timing of spinal surgery relative to diagnosis, treatment history prior to surgery, neurological status, and systemic disease burden were analyzed to determine the impact of these factors on survival outcome.

Results

The authors identified 267 patients who met the study criteria. Five-year overall survival (OS) after spine tumor resection was 7.8%, with a median OS of 11.3 months (95% CI 9.5–13.0 months). Patients with Fuhrman Grade 4 RCC had a median OS of 6.1 months (95% CI 3.5–8.7 months), which was significantly lower than the 14.3 months (95% CI 9.1–19.4 months) observed in patients with Fuhrman Grade 3 or less RCC (p < 0.001). Patients with preoperative neurological deficits had a median survival of 5.9 months (95% CI 4.1–7.7 months), which was significantly lower than the 13.5 months (95% CI 10.4–16.6 months) observed in patients with a normal neurological examination (p < 0.001). Patients whose spine was the only site of metastasis had a median OS of 19 months (95% CI 9.8–28.2 months) after surgery, significantly longer than the 9.7 months (95% CI 8.1–11.3 months) observed in patients with additional extraspinal metastasis sites (p < 0.001). Patients with nonprogressing extraspinal metastasis (no metastasis, stable, or concurrent) had a median survival of 20.6 months (95% CI 15.1–26.1 months), compared with 5.6 months (95% CI 4.4–6.8 months) in patients with progressing metastasis (p < 0.001).

Conclusions

The authors identified several factors influencing survival after spine surgery for metastatic spinal RCC, including grade of the original nephrectomy specimen, activity of the systemic disease, and neurological status at the time of surgery. These clinical features may help to identify patients who may benefit from aggressive surgical intervention.

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Jonathan N. Sellin, Dima Suki, Viraat Harsh, Benjamin D. Elder, Daniel K. Fahim, Ian E. McCutcheon, Ganesh Rao, Laurence D. Rhines and Claudio E. Tatsui

OBJECT

Spinal metastases account for the majority of bone metastases from thyroid cancer. The objective of the current study was to analyze a series of consecutive patients undergoing spinal surgery for thyroid cancer metastases in order to identify factors that influence overall survival.

METHODS

The authors retrospectively reviewed the records of all patients who underwent surgery for spinal metastases from thyroid cancer between 1993 and 2010 at the University of Texas MD Anderson Cancer Center.

RESULTS

Forty-three patients met the study criteria. Median overall survival was 15.4 months (95% CI 2.8–27.9 months) based on the Kaplan-Meier method. The median follow-up duration for the 4 patients who were alive at the end of the study was 39.4 months (range 1.7–62.6 months). On the multivariate Cox analysis, progressive systemic disease at spine surgery and postoperative complications were associated with worse overall survival (HR 8.98 [95% CI 3.46–23.30], p < 0.001; and HR 2.86 [95% CI 1.30–6.31], p = 0.009, respectively). Additionally, preoperative neurological deficit was significantly associated with worse overall survival on the multivariate analysis (HR 3.01 [95% CI 1.34–6.79], p = 0.008). Conversely, preoperative embolization was significantly associated with improved overall survival on the multivariate analysis (HR 0.43 [95% CI 0.20–0.94], p = 0.04). Preoperative embolization and longer posterior construct length were significantly associated with fewer and greater complications, respectively, on the univariate analysis (OR 0.24 [95% CI 0.06–0.93] p = 0.04; and OR 1.24 [95% CI 1.02–1.52], p = 0.03), but not the multivariate analysis.

CONCLUSIONS

Progressive systemic disease, postoperative complications, and preoperative neurological deficits were significantly associated with worse overall survival, while preoperative spinal embolization was associated with improved overall survival. These factors should be taken into consideration when considering such patients for surgery. Preoperative embolization and posterior construct length significantly influenced the incidence of postoperative complications only on the univariate analysis.

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Kelsey L. Watson, Ghadah A. Al Sannaa, Christine M. Kivlin, Davis R. Ingram, Sharon M. Landers, Christina L. Roland, Janice N. Cormier, Kelly K. Hunt, Barry W. Feig, B. Ashleigh Guadagnolo, Andrew J. Bishop, Wei-Lien Wang, John M. Slopis, Ian E. McCutcheon, Alexandar J. Lazar and Keila E. Torres

OBJECTIVE

Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive group of soft tissue sarcomas that can arise sporadically, in the context of neurofibromatosis Type 1 (NF1) or at a site of prior irradiation. Large series profiling the features and outcomes of sporadic, NF1-associated, and radiation-associated MPNSTs are limited. The goal of this study was to elucidate differences between MPNST etiologies in a large single-institution retrospective study.

METHODS

Patients (n = 317) were identified through the tumor registry of The University of Texas MD Anderson Cancer Center. Clinicopathological features were retrospectively collected. Features were compared among MPNST subtypes for patients who had sufficient clinical history (n = 289), and clinicopathological features were used to identify adverse predictors of recurrence and survival outcomes.

RESULTS

Five-year local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and disease-specific survival (DSS) estimates were 56.6%, 49.6%, and 53.6%, respectively, for the high-grade MPNST cohort. Five-year DSS was lower in NF1-associated and radiation-associated MPNST than in sporadic MPNST (52%, 47%, and 67%, respectively, p = 0.140). Patients with radiation-associated MPNST had worse 5-year LRFS than those with the sporadic and NF1-associated subtypes (RT-associated vs sporadic, p = 0.010; RT-associated vs NF1-associated, p = 0.232). Truncally located tumors, positive surgical margins, local recurrence, and metastasis were predictors of adverse DSS in multivariate analysis.

CONCLUSIONS

Radiation-associated MPNSTs are associated with poorer local recurrence-free and disease-specific survival than sporadic and NF1-associated tumors. NF1-associated MPNSTs may have worse survival outcomes owing to large tumor size, compromising truncal location, and lower rate of negative resection margins compared with sporadic tumors.