Neural network modeling for prediction of recurrence, progression, and hormonal non-remission in patients following resection of functional pituitary adenomas.

PURPOSE: Functional pituitary adenomas (FPAs) cause severe neuro-endocrinopathies including Cushing's disease (CD) and acromegaly. While many are effectively cured following FPA resection, some encounter disease recurrence/progression or hormonal non-remission requiring adjuvant treatment. Identification of risk factors for suboptimal postoperative outcomes may guide initiation of adjuvant multimodal therapies. METHODS: Patients undergoing endonasal transsphenoidal resection for CD, acromegaly, and mammosomatotroph adenomas between 1992 and 2019 were identified. Good outcomes were defined as hormonal remission without imaging/biochemical evidence of disease recurrence/progression, while suboptimal outcomes were defined as hormonal non-remission or MRI evidence of recurrence/progression despite adjuvant treatment. Multivariate regression modeling and multilayered neural networks (NN) were implemented. The training sets randomly sampled 60% of all FPA patients, and validation/testing sets were 20% samples each. RESULTS: 348 patients with mean age of 41.7 years were identified. Eighty-one patients (23.3%) reported suboptimal outcomes. Variables predictive of suboptimal outcomes included: Requirement for additional surgery in patients who previously had surgery and continue to have functionally active tumor (p = 0.0069; OR = 1.51, 95%CI 1.12-2.04), Preoperative visual deficit not improved after surgery (p = 0.0033; OR = 1.12, 95%CI 1.04-1.20), Transient diabetes insipidus (p = 0.013; OR = 1.27, 95%CI 1.05-1.52), Higher MIB-1/Ki-67 labeling index (p = 0.038; OR = 1.08, 95%CI 1.01-1.15), and preoperative low cortisol axis (p = 0.040; OR = 2.72, 95%CI 1.06-7.01). The NN had overall accuracy of 87.1%, sensitivity of 89.5%, specificity of 76.9%, positive predictive value of 94.4%, and negative predictive value of 62.5%. NNs for all FPAs were more robust than for CD or acromegaly/mammosomatotroph alone. CONCLUSION: We demonstrate capability of predicting suboptimal postoperative outcomes with high accuracy. NNs may aid in stratifying patients for risk of suboptimal outcomes, thereby guiding implementation of adjuvant treatment in high-risk patients.

Use of Salvage Surgery or Stereotactic Radiosurgery for Multiply Recurrent Skull Base Chordomas: A Single-Institution Experience and Review of the Literature.

Introduction Chordomas are locally destructive neoplasms characterized by appreciable recurrence rates after initial multimodality treatment. We examined the outcome of salvage treatment in recurrent/progressive skull base chordomas. Methods This is a retrospective review of recurrent/progressive skull base chordomas at a tertiary urban academic medical center. The outcomes evaluated were overall survival, progression-free survival (PFS), and incidence of new toxicity. Results Eighteen consecutive patients who underwent ≥1 course of treatment (35.3% salvage surgery, 23.5% salvage radiation, and 41.2% both) were included. The median follow-up was 98.6 months (range 16-215 months). After initial treatment, the median PFS was 17.7 months (95% confidence interval [CI]: 4.9-22.6 months). Following initial therapy, age ≥ 40 had improved PFS on univariate analysis ( p = 0.03). All patients had local recurrence, with 15 undergoing salvage surgical resections and 16 undergoing salvage radiation treatments (mostly stereotactic radiosurgery [SRS]). The median PFS was 59.2 months (95% CI: 4.0-99.3 months) after salvage surgery, 58.4 months (95% CI: 25.9-195 months) after salvage radiation, and 58.4 months (95% CI: 25.9.0-98.4 months) combined. Overall survival for the total cohort was 98.7% ± 1.7% at 2 years and 92.8% ± 5.5% at 5 years. Salvage treatments were well-tolerated with two patients (11%) reporting tinnitus and one patient each (6%) reporting headaches, visual field deficits, hearing loss, anosmia, dysphagia, or memory loss. Conclusion Refractory skull base chordomas present a challenging treatment dilemma. Repeat surgical resection or SRS seems to provide adequate salvage therapy that is well-tolerated when treated at a tertiary center offering multimodality care.

The role of stereotactic radiosurgery in the multimodal management of growth hormone-secreting pituitary adenomas.

Growth hormone (GH)-secreting pituitary adenomas represent a common source of GH excess in patients with acromegaly. Whereas surgical extirpation of the culprit lesion is considered first-line treatment, as many as 19% of patients develop recurrent symptoms due to regrowth of previously resected adenomatous tissue or to continued growth of the surgically inaccessible tumor. Although medical therapies that suppress GH production can be effective in the management of primary and recurrent acromegaly, these therapies are not curative, and lifelong treatment is required for hormonal control. Stereotactic radiosurgery has emerged as an effective adjunctive treatment modality, and is an appealing alternative to conventional fractionated radiation therapy. The authors reviewed the growing body of literature concerning the role of radiosurgical procedures in the treatment armamentarium of acromegaly, and identified more than 1350 patients across 45 case series. In this review, the authors report that radiosurgery offers true hormonal normalization in 17% to 82% of patients and tumor growth control in 37% to 100% of cases across all series, while minimizing adverse complications. As a result, stereotactic radiosurgery represents a safe and effective treatment option in the multimodal management of primary or recurrent acromegaly secondary to GH-secreting pituitary adenomas.

Surgical management of clinically silent thyrotropin pituitary adenomas: A single center series of 20 patients.

Silent thyrotropin pituitary adenomas (TSHomas) are defined by absence of hyperthyroidism despite TSH immunopositivity. Data pertaining to clinical and surgical characteristics of silent TSHomas remains limited. We aim to describe the clinical presentation, pathological characteristics, and outcomes in silent TSHoma patients treated at a tertiary pituitary center. We retrospectively identified patients with histologically-proven silent TSHoma who underwent transsphenoidal resection at our center between 2000 and 2016 (n = 1244 total patients). Patients with preoperative hyperthyroidism or thyroidectomy were excluded. Twenty patients with silent TSHomas were included (1.6% of surgically treated PAs), of which 35% were reoperations. Presenting symptoms included vision loss (45%) and headache (40%). Preoperative pituitary dysfunction included hypothyroidism (40%), hypogonadotropic hypogonadism (30%), and panhypopituitarism (15%). Nineteen patients (95%) had macroadenomas (mean diameter 29.9 mm). Extrasellar growth was identified in 17 patients (85%) and 65% had cavernous sinus invasion. Immunostaining for alpha-subunit was positive in 19 patients (95%), and 75% of tumors expressed immunopositivity for hormones other than TSH. Gross total tumor resection was achieved in 9 patients (45%) on follow-up MRI. Major postoperative complications included hydrocephalus (1 patient) and cerebrospinal fluid leak with meningitis (1 patient). Tumor progression and recurrence occurred in 1 patient each (10% total) over the follow-up period (median 18.5 months). Silent TSHomas tend to be large, invasive tumors. In addition to TSH, a majority express immunopositivity for alpha-subunit and gonadotropins, thereby potentially supporting a primitive adenoma lineage and subtype. Despite reoperation in several patients, good overall outcomes with low complication rates were achieved.

Hemorrhagic Presentation of Rathke Cleft Cysts: A Surgical Case Series.

BACKGROUND: Rathke cleft cysts (RCCs) are benign sellar and suprasellar lesions commonly presenting as asymptomatic incidental findings. Rarely, RCCs hemorrhage and mimic pituitary apoplexy on presentation. OBJECTIVE: To review a series of hemorrhagic RCCs for physicians encountering this rare presentation. METHODS: A database review of >1700 transsphenoidal pituitary operations was performed at the USC Pituitary Center to identify patients with pathologically confirmed RCCs presenting with acute symptoms and evidence of hemorrhage at the time of surgery. Surgical treatment involved transsphenoidal RCC fenestration and drainage. Clinical, endocrine, and imaging outcomes were reviewed. RESULTS: A total of 119 RCCs were identified, and 6 (5.0%) presented with hemorrhage mimicking pituitary apoplexy. Presenting symptoms included acute onset headaches (5/6), vision loss (2/6), and oculomotor nerve palsy (n = 1). Endocrine disturbances at presentation included pre-existing amenorrhea in all female patients (3/3), hypothyroidism (n = 2), panhypopituitarism (n = 2), and one with profound hyponatremia (Na 116 meq/L). All patients underwent endonasal transsphenoidal fenestration and drainage with no major complications. Over mean follow-up of 38.4 mo, 2/2 patients with vision loss reported improvement, and 2/5 patients with headaches reported improvement. Although all women resumed menses, patients with preoperative hypopituitarism did not experience pituitary axis improvement. Follow-up magnetic resonance imaging showed no instances of RCC recurrence with a mean imaging follow-up of 38.6 mo. CONCLUSION: RCCs occasionally present with hemorrhage and clinical symptoms that may be confused with apoplexy. Outcomes following hemorrhagic RCC treatment are excellent when treated at tertiary pituitary centers. Although hyperprolactinemia often improves following surgery, other pituitary axis deficits typically do not.

Recurrent Rathke's Cleft Cysts: Incidence and Surgical Management in a Tertiary Pituitary Center over 2 Decades.

BACKGROUND: Limited data exist pertaining to outcomes following surgery for recurrent Rathke's cleft cysts (RCC). OBJECTIVE: To determine treatment outcomes in patients undergoing reoperation for recurrent or residual RCCs. METHODS: A retrospective analysis of 112 consecutive RCC operations in 109 patients between 1995 and 2017 was conducted. RESULTS: Eighteen patients underwent 21 RCC reoperations with a mean follow-up of 58 mo. Patient symptoms prior to reoperation included headaches (14, 66.7%) and vision loss (12, 57.1%). Thirteen of 18 patients (72.2%) required hormone supplementation prior to reoperation including 5 with diabetes insipidus (DI). Mean RCC diameter was 16 mm and 76% had suprasellar extension. Compared to index RCC cases, intraoperative cerebrospinal fluid leak repair was more common in reoperation cases (15/21, 71% vs 43/91, 47%, P = .05). There was 1 carotid artery injury without neurological sequelae, and 2 postoperative cerebrospinal fluid (CSF) leaks (9.5%). Rates of transient hyponatremia (3/10, 30% vs 4/91, 4.4%, P = .04) and transient DI (5/10, 50% vs 17/91, 18.7%, P = .04) were higher in the reoperation vs index group. Improved headaches and vision were reported in 4/12 (33%) and 8/12 (61.5%) of RCC reoperation patients, respectively. Two patients developed new permanent DI. A higher proportion of reoperation patients had RCC squamous metaplasia (24% vs 5.4%, P = .02) or wall inflammation (42.9% vs 2.2%, P < .001) on pathological examination. CONCLUSION: Reoperation for RCCs is generally safe at tertiary pituitary centers and often results in improved vision. Hypopituitarism is less likely to improve following reoperation for recurrent RCCs. Several histopathological features may help characterize "atypical RCCs" with a higher likelihood of recurrence/progression.

Complications associated with microscopic and endoscopic transsphenoidal pituitary surgery: experience of 1153 consecutive cases treated at a single tertiary care pituitary center.

OBJECTIVEPituitary adenomas (PAs) are benign neoplasms that are frequently encountered during workup for endocrinopathy, headache, or visual loss. Transsphenoidal surgery remains the first-line approach for PA resection. The authors retrospectively assessed complication rates associated with transsphenoidal PA resection from an institutional database.METHODSA retrospective analysis of 1153 consecutive transsphenoidal pituitary adenoma resections performed at the Keck Hospital of USC between November 1992 and March 2017 was conducted. Microscopic transsphenoidal resection was performed in 85.3% of cases, and endoscopic transsphenoidal resection was performed in 14.7%. Analysis of perioperative complications and patient and tumor risk factors was conducted.RESULTSThe overall median hospital stay was 3 days. There was 1 perioperative death (0.1%). Surgical complications included postoperative cerebrospinal fluid leak (2.6%), epistaxis (1.1%), postoperative hematoma (1.1%), meningitis (1.0%), cranial nerve paresis (0.8%), hydrocephalus (0.8%), vision loss (0.6%), stroke (0.3%), abdominal hematoma or infection (0.2%), carotid artery injury (0.1%), and vegetative state (0.2%). Perioperative medical complications included bacteremia/sepsis (0.5%), pneumonia (0.3%), myocardial infarction (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Endocrine complications were the most frequent, including transient diabetes insipidus (4.3%), symptomatic hyponatremia (4.2%), new hypopituitarism (any axis) (3.6%), permanent diabetes insipidus (0.3%), and adrenal insufficiency (0.2%). There were no significant differences between microscopic and endoscopic approaches with regard to surgical complications (6.4% vs 8.8%, p = 0.247) or endocrine complications (11.4 vs 11.8%, p = 0.888). Risk factors for surgical complications included prior transsphenoidal surgery (11.4% vs 6.8%, p = 0.025), preoperative vision loss (10.3% vs 6.8%, p = 0.002), and presence of PA invasion on MRI (8.5% vs 4.4%, p = 0.007).CONCLUSIONSIn this single tertiary center study assessing complications associated with transsphenoidal PA resection, the rate of death or major disability was 0.26%. Risk factors for complications included prior surgical treatment and PA invasion. No differences in complication rates between endoscopic and microscopic surgery were observed. When performed at experienced pituitary centers, transsphenoidal surgery for PAs may be performed with a high degree of safety.

Long-term surgical outcomes following transsphenoidal surgery in patients with Rathke's cleft cysts.

OBJECTIVE: Rathke's cleft cysts (RCCs) are benign epithelial lesions of the sellar region typically treated via a transsphenoidal approach with cyst fenestration and drainage. At present, there is limited evidence to guide patient selection for operative treatment. Furthermore, there is minimal literature describing factors contributing to cyst recurrence. METHODS: The authors conducted a retrospective analysis of 109 consecutive cases of pathology-confirmed RCCs treated via a transsphenoidal approach at a single center from 1995 to 2016. The majority of cases (86.2%) involved cyst fenestration, drainage, and partial wall resection. Long-term outcomes were analyzed. RESULTS: A total of 109 surgeries in 100 patients were included, with a mean follow-up duration of 67 months (range 3-220 months). The mean patient age was 44.6 years (range 12-82 years), and 73% were women. The mean maximal cyst diameter was 14.7 mm. Eighty-eight cases (80.7%) were primary operations, and 21 (19.3%) were reoperations. Intraoperative CSF leak repair was performed in 53% of cases and was more common in reoperation cases (71% vs 48%, p < 0.001). There were no new neurological deficits or perioperative deaths. Two patients (1.8%) developed postoperative CSF leaks. Transient diabetes insipidus (DI) developed in 24 cases (22%) and permanent DI developed in 6 (5.5%). Seven cases (6.4%) developed delayed postoperative hyponatremia. Of the 66 patients with preoperative headache, 27 (44.3%) of 61 reported postoperative improvement and 31 (50.8%) reported no change. Of 31 patients with preoperative vision loss, 13 (48.1%) reported subjective improvement and 12 (44.4%) reported unchanged vision. Initial postoperative MRI showed a residual cyst in 25% of cases and no evidence of RCC in 75% of cases. Imaging revealed evidence of RCC recurrence or progression in 29 cases (26.6%), with an average latency of 28.8 months. Of these, only 10 (9.2% of the total 109 cases) were symptomatic and underwent reoperation. CONCLUSIONS: Transsphenoidal fenestration and drainage of RCCs is a safe and effective intervention for symptomatic lesions, with many patients experiencing improvement of headaches and vision. RCCs show an appreciable (although usually asymptomatic) recurrence rate, thereby mandating serial follow-up. Despite this, full RCC excision is typically not recommended due to risk of hypopituitarism, DI, and CSF leaks.

Recognition and management of delayed hyponatremia following transsphenoidal pituitary surgery.

OBJECT: The goal of this study was to assess the incidence of symptomatic and occult hyponatremia in patients who had undergone transsphenoidal pituitary surgery. METHODS: Patients who underwent transsphenoidal surgery at the University of Southern California University Hospital between 1997 and 2004 had serum sodium levels drawn on an outpatient basis on postoperative Day 7. Patient records were retrospectively reviewed to determine the incidence of, and risk factors for, symptomatic and asymptomatic hyponatremia. Two hundred forty-one patients had routine serum sodium levels drawn as outpatients on postoperative Day 7. Twenty-three percent of these patients were found to be hyponatremic (Na < or =135 mEq/L). The overall incidence rate of symptomatic hyponatremia in the 241 patients was 5%. The majority of hyponatremic patients (80%) remained asymptomatic, whereas 20% became symptomatic. In patients with symptomatic hyponatremia, the mean sodium level at diagnosis was 120.5 mEq/L, compared with 128.4 mEq/L in asymptomatic, hyponatremic patients (p < 0.0001). Female patients were more likely to develop hyponatremia than male patients (33% compared with 22%, p < 0.03). Fifty-two percent of patients who had transient diabetes insipidus (DI) early in their postoperative course subsequently developed hyponatremia, compared with 21% of those who did not have DI (p < 0.001). Patient age, tumor type, and tumor size did not correlate with development of delayed hyponatremia. Outpatients with moderately and severely low sodium levels were 5 and 12.5 times more likely, respectively, to be symptomatic than were patients with mild hyponatremia. CONCLUSIONS: Delayed hyponatremia occurs more frequently than was previously suspected in patients who have undergone transsphenoidal surgery, especially in female patients and those who have previously had transient DI. The majority of hyponatremic patients remain asymptomatic. Obtaining a serum sodium value on an outpatient basis 1 week after pituitary surgery is helpful in recognition, risk stratification, and subsequent intervention, and may prevent potentially serious complications.

Nelson syndrome: historical perspectives and current concepts.

The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

Postoperative Gamma Knife surgery for benign meningiomas of the cranial base.

OBJECT: The standard treatment for meningiomas is complete resection, but the proximity of skull base meningiomas to important neurovascular structures makes complete excision of the lesion difficult or impossible. The authors analyzed the mid- and long-term results obtained in patients treated with postresection Gamma Knife surgery (GKS) for residual or recurrent benign meningiomas of the cranial base. METHODS: Thirty-six patients with residual or recurrent benign meningiomas of the skull base following one or more surgical procedures underwent GKS. There were 31 women and five men, ranging in age from 22 to 73 years. The median tumor volume was 4.1 ml (range 0.8-20 ml) and the median radiation dose to the tumor margin was 16 Gy (range 15-16 Gy). RESULTS: Patients were followed for a median of 81 months (range 30-141 months) after GKS. At the end of the follow-up period, overall neurological improvement was observed in 16 patients (44.4%), whereas the condition in 20 patients (55.6%) was unchanged. One patient suffered transient cerebral edema 6 months after GKS. Based on imaging documentation, a partial response was seen in five patients (13.9%), the disease remained stable in 30 patients (83.3%), and in one patient (2.8%) there was an increase in tumor size. The actuarial progression-free survival rate was 100% at 5 years and 94.7% at 10 years. CONCLUSIONS: Gamma Knife surgery was shown to be an excellent adjunct to resection because of its durable rate of tumor control and low toxicity. It should be initially considered along with surgery for the treatment of complex skull base meningiomas.

Simple closure following transsphenoidal surgery. Technical note.

The most common nonendocrine complication after transsphenoidal surgery is cerebrospinal fluid (CSF) leak. Many neurosurgeons have advocated the routine reconstruction of the floor of the sella turcica using autologous fat, muscle, fascia, and either cartilage or bone after transsphenoidal surgery to prevent postoperative CSF fistulas. However, the use of autologous grafting requires a second incision, prolongs operative time, and adds to the patient's postoperative discomfort. In addition, the presence of sellar packing may interfere with the interpretation of postoperative images. To avoid these disadvantages, the authors suggest that routine sellar reconstruction or closure after transsphenoidal surgery is unnecessary unless an intraoperative CSF leak is encountered. The incidence of postoperative CSF leakage in the patients reported on in this series is no higher than that reported by others, and no other complications such as pneumatocele have been encountered in approximately 2700 patients in whom no intraoperative CSF leak was encountered. The authors conclude that routine closure of the floor of the sella turcica or sphenoid is unnecessary in the absence of intraoperative CSF leak.

Long-term neurological, visual, and endocrine outcomes following transnasal resection of craniopharyngioma.

OBJECT: The authors report on a cohort of patients with craniopharyngioma treated principally through transnasal (TN) resection and followed up for a minimum of 5 years. More specifically, they evaluate the role of the TN approach in the management of craniopharyngioma. METHODS: Between 1984 and 1994, 68 patients underwent TN resection of craniopharyngiomas at the University of Southern California. The tumor was at least partially cystic in 88% of cases. Four tumors were purely intrasellar, 53 had intra- and suprasellar components, and 11 were exclusively suprasellar. During the same period, 18 patients underwent transcranial (TC) resection of purely suprasellar craniopharyngiomas. Long-term neurological, visual, and endocrine outcomes were reviewed for all patients. In 61 (90%) of 68 patients in the TN group, total resection was achieved, according to 3-month postoperative magnetic resonance images, although four patients suffered a recurrence. Three (43%) of the seven tumors that had been partially resected were enlarged on serial imaging. Fifty-four (87%) of 62 patients with preoperative visual loss experienced improvement in one or both eyes, but two patients (3%) with exclusively suprasellar tumors experienced postoperative visual worsening in one or both eyes. New instances of postoperative endocrinopathy (that is, not present preoperatively) occurred as follows: hypogonadism (eight of 22 cases), growth hormone (GH) deficiency (four of 18 cases), hypothyroidism (11 of 49 cases), hypocortisolemia (nine of 52 cases), and diabetes insipidus (DI; four of 61 cases). One case each of hypocortisolemia and hypothyroidism resolved after surgery. Hyperphagia occurred in 27 (40%) of 68 patients. One patient had short-term memory loss. Postoperative complications included one case of cerebrospinal fluid leak. Among the 18 patients in the TC group, 11 had complete resections. In one case (9%) the tumors recurred. Three (43%) of the seven subtotally resected tumors grew during the follow-up interval. Vision improved in 11 (61%) of 18 cases and worsened in three (17%) as a result of surgery. New instances of postoperative endocrinopathy occurred as follows: hypogonadism (one of six cases), GH deficiency (four of seven cases), hypothyroidism (11 of 14 cases), hypocortisolemia (eight of 15 cases), and DI (nine of 16 cases). No instance of preoperative endocrinopathy was corrected through TC surgery. Four patients (22%) exhibited short-term memory loss and 11 (61%) had hyperphagia after surgery. When compared with those in the TC group, patients in the TN group had shorter hospital stays. CONCLUSIONS: Use of the TN approach can render good outcomes in properly selected patients with craniopharyngioma, particularly when the tumor is cystic. Even in mostly suprasellar cases, an extended TN approach can afford complete resection. Note that endocrine function often worsens after surgery and that postoperative obesity can be a significant problem.

Surgical outcomes in 118 patients with Rathke cleft cysts.

OBJECT: Microscopic Rathke cleft cysts are a common incidental autopsy finding, but some Rathke cleft cysts can become sufficiently large to cause visual impairment, hypothalamic-pituitary dysfunction, and headaches. In this study patients were evaluated pre- and postoperatively to ascertain the clinical significance of surgical intervention on endocrine and visual improvement. Factors correlated with cyst recurrence were also evaluated. METHODS: A retrospective analysis was conducted in 160 patients with Rathke cleft cysts who were treated between 1984 and 1995 and completed at least a 5-year follow-up period. Of these 160 patients, 118 initially exhibited symptoms of visual impairment or endocrine dysfunction, became symptomatic during the follow-up period, or were found to have cyst enlargement. These 118 patients underwent transsphenoidal surgery. Forty-two patients with incidental lesions that demonstrated no growth on magnetic resonance (MR) images were followed up without an operation. Complete resection, as observed on MR images 3 months postoperatively, was obtained in 114 (97%) of 118 patients. Vision improved postoperatively in 57 (98%) of 58 patients. Hypogonadism improved in 11 (18%) of 62 patients, growth hormone deficiency resolved in 14 (18%) of 78 patients, and hypocortisolemia resolved in one (14%) of seven patients. Twenty-two patients (19%) began to exhibit symptoms of diabetes insipidus, which had not been present preoperatively. The total 5-year recurrence rate was 18% (21 of 118 patients), with 12 patients requiring a repeated operation. Surgical and pathological factors that were found to be statistically associated with recurrence were the use of a fat and/or fascial graft for closure (p < 0.01) and the presence of squamous metaplasia in the cyst wall (p < 0.01). The extent of resection of the cyst wall was not associated with an increased rate of recurrence. In 42 (69%) of 61 patients the incidental cysts did not progress on imaging studies or clinically. CONCLUSIONS: This is the largest series of patients with symptomatic Rathke cleft cysts who received operative intervention and participated in the longest postoperative follow up reported in the literature. The high recurrence rate (18%) supports the theory that a relationship exists between a symptomatic Rathke cleft cyst and craniopharyngioma. Improvements in visual and endocrine dysfunction can be expected after surgical decompression of the optic apparatus and the hypothalamic-pituitary axis.

Tamoxifen-induced growth arrest and apoptosis in pituitary tumor cells in vitro via a protein kinase C-independent pathway.

Protein kinase C (PKC), a kinase family involved in cell signal transduction, is overexpressed in most pituitary adenoma cells. We studied the effect of tamoxifen, an estrogen receptor antagonist and also a protein kinase inhibitor, on pituitary tumor cell proliferation and the induction of apoptosis; and we compared its effects with those of another PKC inhibitor, staurosporine. Tamoxifen induced growth arrest and apoptosis in a mouse pituitary adenoma cell line, AtT20, and in low-passage human primary pituitary tumor cell cultures. Staurosporine also inhibited pituitary tumor cell growth. PKC activity in AtT20 cells was inhibited by staurosporine and by prolonged treatment with phorbol myristate acetate, which down-regulates PKC activity, but not by tamoxifen, at the dosages used to induce apoptosis. Our findings suggest that tamoxifen induces apoptosis in AtT20 cells independent of a classical PKC isozyme pathway.

Variations on the standard transsphenoidal approach to the sellar region, with emphasis on the extended approaches and parasellar approaches: surgical experience in 105 cases.

OBJECTIVE: The traditional boundaries of the transsphenoidal approach may be expanded to include the region from the cribriform plate of the anterior cranial base to the inferior clivus in the anteroposterior plane, and laterally to expose the cavernous cranial nerves and the optic canal. We review our combined experience with these variations on the transsphenoidal approach to various lesions of the sellar and parasellar region. METHODS: From 1982 to 2003, we used the extended and parasellar transsphenoidal approaches in 105 patients presenting with a variety of lesions of the parasellar region. This study specifically reviews the breadth of pathological lesions operated and the complications associated with the approaches. RESULTS: Variations of the standard transsphenoidal approach have been used in the following series: 30 cases of pituitary adenomas extending laterally to involve the cavernous sinus, 27 craniopharyngiomas, 11 tuberculum/diaphragma sellae meningiomas, 10 sphenoid sinus mucoceles, 18 clivus chordomas, 4 cases of carcinoma of the sphenoid sinus, 2 cases of breast carcinoma metastatic to the sella, and 3 cases of monostotic fibrous dysplasia involving the clivus. There was no mortality in the series. Permanent neurological complications included one case of monocular blindness, one case of permanent diabetes insipidus, and two permanent cavernous cranial neuropathies. There were four cases of internal carotid artery hemorrhage, one of which required ligation of the cervical internal carotid artery and resulted in hemiparesis. The incidence of postoperative cerebrospinal fluid fistulae was 6% (6 of 105 cases). CONCLUSION: These modifications of the standard transsphenoidal approach are useful for lesions within the boundaries noted above, they offer excellent alternatives to transcranial approaches for these lesions, and they avoid prolonged exposure time and brain retraction. Technical details are discussed and illustrative cases presented.

Zones of approach for craniofacial resection: minimizing facial incisions for resection of anterior cranial base and paranasal sinus tumors.

OBJECTIVE: Anterior cranial base tumors are surgically resected with combined craniofacial approaches that frequently involve disfiguring facial incisions and facial osteotomies. The authors outline three operative zones of the anterior cranial base and paranasal sinuses in which tumors can be resected with three standard surgical approaches that minimize transfacial incisions and extensive facial osteotomies. METHODS: The zones were defined by performing dissections on 10 cadaveric heads and by evaluating radiographic images of patients with anterior cranial base tumors. The three approaches performed on each cadaver were transbasal, transmaxillary, and extended transsphenoidal. RESULTS: Three zones of approach were defined for accessing tumors of the anterior cranial base, nasal cavity, and paranasal sinuses. Zone 1 is exposed by the transbasal approach, which is limited anteriorly by the supraorbital rim, posteriorly by the optic chiasm and clivus, inferiorly by the palate, and laterally by the medial orbital walls. This approach allows access to the entire anterior cranial base, nasal cavity, and the majority of maxillary sinuses. The limitation imposed by the orbits results in a blind spot in the superolateral extent of the maxillary sinus. Zone 2 is exposed by a sublabial maxillotomy approach and accesses the entire maxillary sinus, including the superolateral blind spot and the ipsilateral anterior cavernous sinus. However, access to the anterior cranial base is limited. Zone 3 is exposed by the transsphenoidal approach. This approach accesses the midline structures but is limited by the lateral nasal walls and intracavernous carotid arteries. An extended transsphenoidal approach allows further exposure to the anterior cranial base, clivus, or cavernous sinuses. The use of the endoscope facilitates tumor resection in the nasal cavity and paranasal sinuses. CONCLUSION: The operative zones outlined offer minimally invasive craniofacial approaches to accessing lesions of the anterior cranial base and paranasal sinuses, obviating facial incisions and facial osteotomies. Case illustrations demonstrating the approach selection paradigm are presented.