Early results of surgery in patients with nonfunctioning pituitary adenoma and analysis of the risk of tumor recurrence

OBJECT: Nonfunctioning pituitary adenomas (NFPAs) are benign tumors of the pituitary gland that typically cause visual and/or hormonal dysfunction. Surgery is the treatment of choice, but patients remain at risk for tumor recurrence for several years afterwards. The authors evaluate the early results of surgery and the long-term risk of tumor recurrence in patients with NFPAs. METHODS: Between 1990 and 2005, 491 previously untreated patients with NFPA underwent surgery at the Università Vita-Salute. Determinations of recurrence or growth of the residual tumor tissue during the follow-up period were based on neuroradiological criteria. RESULTS: Residual tumor after surgery was detected in 173 patients (36.4%). Multivariate analysis showed that invasion of the cavernous sinus, maximum tumor diameter, and absence of tumor apoplexy were associated with an unfavorable surgical outcome. At least 2 sets of follow-up neuroimaging studies were obtained in 436 patients (median follow-up 53 months). Tumors recurred in 83 patients (19.0%). When tumor removal appeared complete, younger age at surgery was associated with a risk of tumor recurrence. In patients with incomplete tumor removal, adjunctive postoperative radiotherapy had a marked protective effect against growth of residual tumor. CONCLUSIONS: Complete surgical removal of NFPAs can be safely achieved in > 50% of cases. Visual symptoms and, less frequently, pituitary function may improve after surgery. However, tumor can recur in patients after apparently complete surgical removal. In patients with incomplete tumor removal, radiation therapy is the most effective adjuvant therapy for preventing residual tumor growth.     

Long-term Outcomes of Hypofractionated Stereotactic Radiotherapy for the Treatment of Perioptic Nonfunctioning Pituitary Adenomas

The efficacy of stereotactic radiotherapy (SRT) has been well established for postoperative residual and recurrent nonfunctioning pituitary adenomas (NFPAs). However, the risk of visual impairment due to SRT for lesions adjacent to the optic pathways remains a topic of debate. Herein, we evaluated the long-term clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for perioptic NFPAs. From December 2002 to November 2015, 32 patients (18 males and 14 females; median age 63 years; range, 36–83 years) with residual or recurrent NFPAs abutting or displacing the optic nerve and/or chiasm (ONC) were treated with HFSRT. The median marginal dose was 31.3 Gy (range, 17.2–39.6) in 8 fractions (range, 6–15). Magnetic resonance imaging (MRI) and visual and hormonal examinations were performed before and after HFSRT. The median follow-up period was 99.5 months (range, 9–191). According to MRI findings at the last follow-up, the tumor size had decreased in 28 (88%) of 32 patients, was unchanged in 3 (9%), and had increased in 1 (3%). The successful tumor size control rate was 97%. Visual functions remained unchanged in 19 (60%) out of 32 patients, improved in 11 (34%), and deteriorated in 2 (6%). Two patients had deteriorated visual functions; no complications occurred because of the HFSRT. One patient developed hypopituitarism that required hormone replacement therapy. The result of this long-term follow-up study suggests that HFSRT is safe and effective for the treatment of NFPAs occurring adjacent to the ONC.     

Nonfunctioning pituitary adenomas: association of Ki-67 and HMGA-1 labeling indices with residual tumor growth

Background

The postoperative biological behavior of nonfunctioning pituitary adenomas (NFPAs) is variable. Some residual NFPAs are stable long-term, others grow, and some recur despite complete removal. The usual histological markers of tumor aggressiveness are often similar between recurring, regrowing, and stable tumors, and therefore are not reliable as prognostic parameters. In this study, the clinical utility of proliferation indices (labeling index, Li) based on immunohistochemistry targeted at antigens Ki-67 and High-mobility group A1 (HMGA-1) for prediction of NFPA prognosis was investigated.

Methods

Fifty patients with NFPAs were investigated. In each patient, Ki-67 and HMGA-1 Li were evaluated. Based on postoperative magnetic resonance images, patients were classified as tumor-free (18 patients), or harboring a residual tumor (32 patients). The latter group was further subdivided into groups with stable tumor remnants (11 patients) or progressive tumor remnants (21 patients).

Results

The median follow-up period was 8 years. No significant relationship between HMGA-1 Li and residual tumor growth was found. Growing residual tumors showed a trend towards higher Ki-67 Li compared with stable ones (p?=?0.104). All tumor remnants with Ki-67 Li above 2.2 % were growing. The relationship between residual tumor growth and Ki-67 Li exceeding the cutoff value of 2.2 % was significant (p?=?0.01 in univariate, p?=?0.044 in multivariate analysis).

Conclusions

The prognostic significance of the HMGA-1 antigen was not confirmed. In contrast, the Ki-67 Li provides useful and valuable information for the postoperative management of NFPAs. In residual adenomas with a Ki-67 Li above 2.2 %, regrowth should be expected, and these tumors may require shorter intervals of follow-up magnetic resonance imaging (MRI) and/or early adjuvant therapy. Future larger studies are needed to confirm the results of this study.     

Neurosurgery and pituitary tumors: surgical indications and outcome

TWO MAIN FEATURE: Indication for surgery in patients with pituitary tumors depends first on the anatomical situation: the enclosed or invasive nature of the tumor. Total resection of an enclosed tumor, even if it is a huge one, can be expected to be successful. For invasive tumors, surgery will be subtotal unless the invasion is very limited. The second consideration is the efficacy and limitations of medical treatment. At present, only secreting pituitary adenomas are accessible to medical therapy. Other pituitary tumors, and non-functioning pituitary adenomas are not suitable for valid medical treatment and may warrant a surgical strategy. CHOICE OF THE OPERATIVE APPROACH: Anatomical and radiological considerations are determining. For secreting pituitary adenomas, first intention surgery via a transphenoidal access is advocated when surgery can be expected to achieve complete tumor resection without damaging the normal gland. For other cases, medical treatment has to be instituted prior to surgery which will be discussed in case of failure, intolerance or for tumor reduction. Transphenoidal surgery is strongly advocated in case of a pituitary incidentaloma with a visual danger, even in old patients. OUTCOME: Visual symptoms are often improved after neurosurgery for pituitary tumors. Hormone cure is frequent in microsecreting pituitary adenomas, rarely in invasive tumors.     

Proliferation index of nonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results

OBJECTIVE: The recurrence of nonfunctioning pituitary adenomas (NFPAs) after surgical removal is common. The aim of our study was to investigate and correlate the growth fraction of NFPAs with clinical characteristics and long-term follow-up results. METHODS: Tumor specimens were obtained from 101 consecutive patients with NFPAs (48 female patients and 53 male patients; mean age, 52.0 +/- 1.5 yr). Specimens were immediately fixed in 10% buffered formalin and then embedded in paraffin. The Ki-67 antigen was assessed by immunocytochemical analysis using the monoclonal antibody MIB-1. The Ki-67 antigen labeling index (LI) was determined by counting a total of at least 1,000 neoplastic nuclei. RESULTS: The mean Ki-67 LI for the 101 patients was 2.4 +/- 0.3% (range, 0-23.0%). Only age at surgery was inversely correlated with the Ki-67 LI; sex, maximal tumor diameter, and invasiveness into the cavernous sinuses did not significantly affect the Ki-67 LI. The mean follow-up period was 39.7 +/- 2.1 months. During follow-up monitoring, 23 patients experienced tumor recurrence, after a mean period of 28.6 +/- 4.8 months. Invasiveness of the tumor on preoperative magnetic resonance imaging scans was the strongest predictor of late tumor recurrence, followed by previous pituitary surgery, younger age, and lack of postoperative radiotherapy. The Ki-67 LI had no independent prognostic value. CONCLUSION: Our study suggests that the clinical characteristics of patients with NFPAs, except for age at surgery, are not correlated with the Ki-67 LI. Moreover, the Ki-67 LI does not seem to provide independent information to identify patients at high risk for tumor recurrence.     

High-Field iMRI in transsphenoidal pituitary adenoma surgery with special respect to typical localization of residual tumor

Background

Intraoperative high-field magnetic resonance imaging (iMRI) is used as an immediate intraoperative quality control, evaluating the extent of tumor removal during the surgical procedure and allowing us to extend resections in those cases where tumor remnants are documented. The aim of the study was to analyze the typical localization of residual tumor remnants, detected by iMRI during transsphenoidal surgery of pituitary adenomas.

Methods

We reviewed a series of 72 patients. All patients presented with macroadenomas with or without suprasellar extension. After high-field MRI investigation, we divided the series preoperatively into totally resectable (TR) and non-totally resectable (NTR) tumors. Tumor remnants were documented by iMRI, obtained directly after tumor removal, as well as by intraoperative surgical inspection of the sellar content.

Results

In the TR group, we observed 23 cases suspicious for tumor remnants, located anteriorly, laterally, posteriorly, and suprasellar under descending folds of the diaphragm. Continuing surgery, upon a “second inspection”, tumor resection could be completed in all cases.

Conclusions

Incomplete removal of resectable pituitary adenomas could be avoided in a higher number of cases with the knowledge of the location of the typical remnant tumors. In those cases where it is not possible to achieve a complete resection of adenoma, further treatment can be planned at an earlier stage, without any need to wait for the conventional postoperative MRI scan performed 2 to 3 months after surgery.     

Imaging of Resected Nonfunctioning Pituitary Adenomas: The Cost of Surveillance

Objectives To determine the cost of annual magnetic resonance imaging (MRI) surveillance after resection of nonfunctioning pituitary adenomas (NFPAs) and its effectiveness in reducing visual compromise due to tumor recurrence. Design Retrospective case series. Setting Vanderbilt University Medical Center (2003–2011). Participants A total of 120 patients underwent primary transsphenoidal resection and surveillance of NFPAs between 2003 and 2011. Main Outcome Measures Time from initial surgery to most recent imaging or progression. Surveillance MRI costs according to Centers for Medicare and Medicaid database and visual field deficits. Results Patients received 382 surveillance scans at a total cost of $218,477.30. The median follow-up was 47 months (interquartile range [IQR]: 26–76), and the median interval between scans was 357 days (IQR: 225–434). Overall, 50 scans (13%) revealed tumor growth. The cost per scan revealing growth was $4,369.55. The cost to identify 19 patients (16%) with clinically significant growth was $11,498.80 per patient. A total of 5 of 19 patients (26%) experienced new visual deficits prior to intervention. Patients with visual decline tended to have longer scan intervals than those with preserved vision (mean: 239 versus 794 days; p = 0.0584). No patient with annual surveillance imaging experienced visual decline. Conclusions Annual MRI scans are a sensitive and cost-conscious method to identify NFPA recurrence prior to visual decline.     

TSH-Secreting Pituitary Adenoma: Current Management and Review

The neurosurgical literature contains little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide in such cases. While TSH-secreting pituitary adenomas are rare, our review and illustrative case demonstrate the effectiveness of pretreating patients with octreotide therapy not only to reduce tumor size prior to surgical resection but also to increase the possibility of clinical remission.

A 52-year-old male presented with signs and symptoms of hyperthyroidism and elevated TSH, thyroxine, and triiodothyronine. Magnetic resonance imaging revealed a pituitary macroadenoma with extension into the suprasellar cistern. The patient was treated with octreotide for 6 months prior to surgery. Approximately 3 months after initiation of octreotide therapy, the patient exhibited excellent biochemical and clinical response. Tumor shrinkage of nearly 50% was associated with resolution of suprasellar extension and optic nerve compression. Subsequent transsphenoidal surgery for resection of residual adenoma was followed by symptomatic and hormonal remission without the need for reinstitution of octreotide therapy.

Pretreatment with octreotide for TSH-secreting pituitary adenomas has a beneficial effect on disease symptoms and reduces tumor mass. We suggest that patients with these rare tumors can be managed with a combination of octreotide therapy and subsequent surgical removal of residual tumor. Although this combination treatment helps to facilitate clinical remission, only short-term follow-up has been reported and thus the optimal management of these patients remains to be determined.

     

Preliminary visual field preservation after staged CyberKnife radiosurgery for perioptic lesions

OBJECTIVE: The limited radiation tolerance of the optic nerves and the optic chiasm makes it a challenge to treat immediately adjacent lesions with radiosurgery. Staged or hypofractionated radiosurgery has the virtue of combining the accuracy and conformality of radiosurgery with the normal tissue-sparing benefits of fractionation. We describe a consecutive series of patients with meningiomas and pituitary adenomas abutting the anterior visual pathways who were treated with staged, image-guided radiosurgery. METHODS: Thirty-four patients with either meningiomas (20 patients) or pituitary adenomas (14 patients) within 2 mm of the optic apparatus were treated. Several patients had previously been treated with conventional fractionated radiotherapy (5 patients) or subtotal surgical resection (23 patients). Radiosurgery was delivered in two to five stages to a cumulative average marginal dose of 20.0 Gy. Visual testing and clinical examinations were performed before treatment and at follow-up intervals beginning at 6 months after treatment. RESULTS: The mean follow-up period was 29 months (range, 15-62 mo). Pre- and posttreatment vision was unchanged in 20 patients, improved in 10, and worse in 3. One patient died during follow-up as a result of an unrelated cardiac event. Visual loss was accompanied by tumor progression in two cases. In a third patient with a multiply recurrent adrenocorticotropic hormone-secreting pituitary adenoma, injury to one optic nerve occurred after both a prior course of radiotherapy and three separate sessions of radiosurgery. CONCLUSION: Staged radiosurgery resulted in high rates of tumor control and preservation of visual function. Ninety-one percent of patients retained their presurgical vision. Staged radiosurgery may be a safe and effective alternative to either surgery or fractionated radiotherapy for selected lesions adjacent to the optic apparatus.     

Growth pattern and rate in residual nonfunctioning pituitary adenomas: correlations among tumor volume doubling time,patient age,and MIB-1 index

OBJECT: Surgical cure can be achieved in pituitary adenomas when they are completely removed. It is controversial whether postoperative radiation therapy should be given to prevent recurrence, and whether an early reoperation should be performed for residual adenomas, because we have little information about the natural history of postoperative residual adenomas. METHODS: The residual tumor volume was serially measured in 40 nonfunctioning pituitary adenomas (NFPAs) and the tumor volume doubling time (TVDT) was calculated. Correlations between the patients' age, tumor volume, log TVDT, and MIB-1 index were examined. Other factors including the patient's sex, cavernous sinus (CS) invasion by the tumor, or presence of an intratumoral cyst were analyzed to assess their influence on the TVDT. Values are expressed as the means +/- standard deviations. Thirty-eight adenomas increased in volume and two decreased during a follow-up period ranging from 4 to 141 months (mean 52.5 months). Exponentially linear tumor growth was observed in the 38 growing adenomas regardless of the residual tumor volume, with the TVDT ranging from 506 to 5378 days (mean 1836 days). The patients' age was 57.1 +/- 15.7 years (range 15-79 years), the tumor volume at the beginning of the magnetic resonance imaging observation period was 2.5 +/- 2.2 cm3 (range 0.07-14.5 cm3), and the MIB-1 index was 0.73 +/- 0.68% (range 0.1-2.9%). There was a correlation between the log TVDT and patient age (R = 0.73), an inverse correlation between the log TVDT and MIB-1 index (r = -0.49), and an inverse correlation between the MIB-1 index and patient age (r = -0.61). A significant difference (p = 0.0001) was noted between the TVDT (1,106 days) in the 19 patients younger than 61 years of age and the TVDT (2566 days) in the 19 patients who were 61 years of age or older. There was also a significant difference (p = 0.0002) between the age (50.8 +/- 15.3 years) of the patients with rapidly growing tumors (TVDT < 1,836 days, 24 patients) and the age (69.1 +/- 7.6 years) of the patients with slowly growing tumors (TVDT> 1836 days, 14 patients). Other factors including the patients' sex, CS invasion, and intratumoral cyst formation did not affect the TVDT of residual NFPAs. CONCLUSIONS: The tumor growth rate of residual NFPAs is strongly influenced by the patient's age. The TVDT in elderly patients is much longer than that previously reported. Treatment strategies that take into consideration the natural history of residual adenomas should be established especially in the elderly population.     

Surgical removal of growth hormone-secreting pituitary adenomas with intensive microsurgical pseudocapsule resection results in complete remission of acromegaly

Although some investigators recommended surgical removal of the borders between pituitary adenoma and the surrounding normal pituitary gland, there is so far little documentation of how intensive dissection of the border zone affects the actual clinical remission rate of pituitary adenomas. We investigated the precise histological characteristics of the boundary, using surgical specimens from patients who underwent intensive resection of microsurgical pseudocapsule of growth hormone (GH)-secreting pituitary adenomas. Furthermore, we compared the remission rate of acromegaly between subjects with (Group 1) and without (Group 2) intensive resection of microsurgical pseudocapsule in order to correlate the histological complete resection and endocrinological remission. Histologically, most adenomas were in direct contact with normal pituitary gland that formed an increased fibrous component facing the adenoma, without a true histological pseudocapsule. It was impossible to dissect the tumor at exactly the tumor–normal pituitary interface for the whole extent of the pituitary adenoma during surgery, and complete removal of the tumor inevitably included a portion of normal tissue (microsurgical pseudocapsule). The biochemical remission rate was significantly higher in Group 1 than in Group 2 (90.0 vs 61.1%), and Group 1 showed no additional postoperative pituitary hypofunction. The present results suggested that intensive resection of the microsurgical pseudocapsule is essential to accomplish histological and endocrinological total resection of the GH-secreting pituitary adenomas for remission of acromegaly.     

TSH-Secreting Pituitary Adenoma: Current Management and Review

The neurosurgical literature contains little information about the current management of patients with thyroid-stimulating hormone (TSH)-secreting pituitary adenomas or about the usefulness of the somatostatin analogue octreotide in such cases. While TSH-secreting pituitary adenomas are rare, our review and illustrative case demonstrate the effectiveness of pretreating patients with octreotide therapy not only to reduce tumor size prior to surgical resection but also to increase the possibility of clinical remission.A 52-year-old male presented with signs and symptoms of hyperthyroidism and elevated TSH, thyroxine, and triiodothyronine. Magnetic resonance imaging revealed a pituitary macroadenoma with extension into the suprasellar cistern. The patient was treated with octreotide for 6 months prior to surgery. Approximately 3 months after initiation of octreotide therapy, the patient exhibited excellent biochemical and clinical response. Tumor shrinkage of nearly 50% was associated with resolution of suprasellar extension and optic nerve compression. Subsequent transsphenoidal surgery for resection of residual adenoma was followed by symptomatic and hormonal remission without the need for reinstitution of octreotide therapy.Pretreatment with octreotide for TSH-secreting pituitary adenomas has a beneficial effect on disease symptoms and reduces tumor mass. We suggest that patients with these rare tumors can be managed with a combination of octreotide therapy and subsequent surgical removal of residual tumor. Although this combination treatment helps to facilitate clinical remission, only short-term follow-up has been reported and thus the optimal management of these patients remains to be determined.     

Long-term recurrence and mortality after surgery and adjuvant radiotherapy for nonfunctional pituitary adenomas

OBJECT: Long-term outcomes following surgery for nonfunctional pituitary adenomas (NFPAs) are unclear. The role of adjuvant radiation therapy is therefore controversial because it is associated with higher tumor control but also carries known long-term morbidity. The authors' aim was to determine predictors of recurrence and overall survival and to define patient subgroups that may benefit from radiotherapy. METHODS: The authors performed a retrospective cohort analysis of 663 patients who underwent surgery between 1975 and 1995 for treatment of primary NFPAs. The main outcome measures were disease progression after surgery, defined by clinical and/or imaging criteria, and all-cause mortality. RESULTS: Over a median clinical follow-up of 8.4 years, there were 64 (9.7%) recurrences after treatment, with a median time to recurrence of 5.6 years. The 5-, 10-, and 15-year recurrence-free probabilities were 0.93, 0.87, and 0.81, respectively. Multivariate Cox proportional hazard regression analysis identified the following predictors as associated with increased recurrence: cavernous sinus invasion (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.5-6.4; p < 0.001) and subtotal resection (STR) without radiotherapy (HR 3.6, 95% CI 1.4-14; p = 0.01). Using time-to-event estimates to adjust for differences in follow-up between groups, radiotherapy was found to reduce tumor recurrence in only those patients who received an STR (p < 0.001, log-rank test) but not gross-total resection (GTR; p = 0.63, log-rank test). Median follow-up for overall survival was 14.0 years. The 5-, 10-, 15- and 20-year overall survival estimates were 0.91, 0.81, 0.69, and 0.55, respectively. Within the study cohort and in age- and sex-adjusted comparison with the general US population, increased relative mortality was observed in patients who underwent radiotherapy or STR. CONCLUSIONS: Cavernous sinus invasion is an important prognostic variable for long-term control of NFPAs. Radiotherapy results in long-term tumor control for patients who undergo STR but does not affect recurrence rates and may increase the risk of death after GTR. Given the risks associated with radiotherapy, there is no role for its routine application in patients who have undergone GTR of their NFPA. In all patients, long-term monitoring is required.     

Endoscopic vs. microscopic transsphenoidal surgery outcomes in 514 nonfunctioning pituitary adenoma cases

Transsphenoidal surgery remains the preference choice for patients with nonfunctioning pituitary tumors at present, but the superiority of surgical modalities is still debated. Moreover, the efficacy of microscopic and endoscopic transsphenoidal surgery has not been fully studied. Therefore, the present study was designed to compare the postoperative outcomes of the two widely used approaches worldwide. This retrospective study included 514 patients with the first transsphenoidal pituitary adenoma resection in Shandong Provincial Hospital from January 2015 to July 2020 and compared the outcomes of microscope transsphenoidal surgery (MTSS) and endoscopy transsphenoidal surgery (ETSS). A total of 514 patients were included in this study, of whom 210 received the ETSS and 304 received the MTSS. The patients in two groups were similar in terms of postoperative hyponatremia (p?=?0.229), diabetes insipidus (p?=?0.264), the recovery of hormonal axis (p?<?0.05), and extent of resection (EOR) (p?=?0.067). ETSS was more likely to cause cerebrospinal fluid leakage than MTSS (p?=?0.017, 3.6% vs. 8.6%). CSF leakage might be related to tumor size (95% CI?=?1.305–2.766, p?=?0.001), and the surgeon’s transsphenoidal surgery volume?<?300 was also a risk factor (95% CI?=?1.396–9.067, p?=?0.008). The effect of different surgeries on postoperative vision improvement was statistically difference in univariate analysis (p?=?0.048) but not after adjustment for confounders (p?=?0.112). Furthermore, there were statistical difference in EOR between MTSS and ETSS when adenomas were performed suprasellar extension (p?=?0.037) or optic chiasm compression (p?=?0.045). Both techniques are valid for the treatment of nonfunctional adenomas. But CSF leakage is more likely after ETSS. In addition, ETSS is more conducive to resection of nonfunctional adenomas with suprasellar extension or optic chiasm compression.

     

Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors

OBJECT: The presence of a histological pseudocapsule around pituitary tumors was noted in the early 1900s. Since that time there has been no emphasis on the sequence of the stages of its development or on the relationship between these stages and the capacity to identify very small pituitary tumors at surgery in patients in whom preoperative imaging has been nondiagnostic. In addition, limited emphasis has been given to the pseudocapsule's use for selective and complete resection of pituitary adenomas. METHODS: The development of the pseudocapsule was examined by performing histological analysis of portions of pituitary glands removed during 805 operations for Cushing disease. Twenty-five adenomas, each measuring between 0.25 and 4 mm in maximum diameter, were detected in the excised specimens; 17 were adenocorticotropic hormone-positive adenomas and eight were incidental tumors (four prolactin-secreting and four nonsecreting lesions). In 16 tumors the size of the adenoma could be established. The distribution of tumor size in relation to the presence of a histological pseudocapsule indicates a transition from the absence of a reticulin capsule (tumor diameter < or =1 mm) through the initial compression of surrounding tissue (tumor diameter 1-2 mm) to the presence of a multilayered reticulin capsule observed when adenomas become larger (tumor diameter 2-3 mm). CONCLUSIONS: The absence of a reticulin capsule in cases of very small tumors may contribute to limited localization of these lesions during surgical exploration of the pituitary gland. In this article the authors describe surgical techniques in which the histological pseudocapsule is used as a surgical capsule during pituitary surgery. In their experience, recognition of this surgical capsule and its use at surgery has contributed to the identification of microadenomas buried in the pituitary gland, aided the recognition of subtle invasion of the pituitary capsule and contiguous dura mater, and enhanced the consistency of complete tumor excision with small and large tumors.     

The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery

OBJECT: Pituitary adenomas are considered benign tumors; however, they may infiltrate surrounding tissues including the dura mater. In this paper the authors analyze the clinical significance of microscopically confirmed dural invasion by comparing a range of variables (age and sex of patients, adenoma type, adenoma size on magnetic resonance [MR] images, remission, residual pituitary disease, recurrence, survival, and disease-free interval after surgery) between patients with noninvasive adenomas and those with invasive ones. METHODS: Between 1992 and 1997 dural specimens were obtained in 354 patients with pituitary adenomas who underwent transsphenoidal surgery performed by the senior author (E.R.L.). Dural specimens were examined using routine histological methods and assessed for invasion by pituitary adenoma tissue. The dura was invaded by the pituitary adenoma in 161 patients (45.5%), and in 192 patients (54.5%) no evidence of dural invasion was found. Dural invasion was present significantly more frequently in the repeated surgery group (69%, 55 patients) than in the primary transsphenoidal surgery group (41%, 291 patients). The mean age of patients undergoing primary transsphenoidal surgery was significantly older in cases of invasive adenomas (50 years) compared with cases of noninvasive adenomas (43 years), and these age differences also correlated with adenoma size. Women tend to develop clinically evident, smaller adenomas at a younger age than men. Of the patients with pituitary adenomas that were 20 mm or smaller, 117 (76%) of 154 were women, whereas of the patients with adenomas that were larger than 20 mm, 74 (54%) of 137 were men. The frequency of dural invasion increased with increasing size of the pituitary adenoma as measured on MR images. In 291 patients who underwent primary pituitary surgery, the frequency of dural invasion according to adenoma size was 24% (< or = 10 mm), 35% (> 10 to < or = 20 mm), 55% (> 20 to < or = 40 mm), and 70% (> 40 mm). In patients who underwent primary transsphenoidal surgery, dural invasion was present in more than 50% of those with nonfunctioning adenomas and in 30 to 35% of patients with endocrinologically active adenomas. The mean diameter of the gonadotrophic adenomas and null-cell adenomas was significantly larger than that of each of the endocrinologically active adenomas. In 58 (20%) of 291 patients who underwent primary pituitary surgery there was residual pituitary disease postsurgery, and 20% of this subset of patients showed clinical improvement to such an extent that no further management was recommended. After pituitary surgery, residual tumor tissue was demonstrable significantly more frequently in patients with invasive adenomas than in those with noninvasive adenomas. Recurrences after initial remission (cure) of pituitary disease occurred in 18 (8.8%) of 205 patients between 2 and 79 months after primary pituitary surgery (median 25 months). The recurrence rate was not related to dural invasion in a consistent or significant fashion. Seven patients died between 14 and 79 months after pituitary surgery and all had invasive adenomas identified on gross observation at surgery and on microscopy. The survival rate was slightly but significantly decreased for patients with invasive adenomas (91%) compared with patients with noninvasive adenomas (100%) at 6 years postsurgery. CONCLUSIONS: The principal significance of dural invasion by pituitary adenoma is the persistence of tumor tissue after transsphenoidal surgery (incomplete adenomectomy; 20% in primary pituitary tumor resections). The increase in adenoma size with time and the concurrent development of dural invasion are the major factors that determine an incomplete adenomectomy. When the adenoma remains restricted to the sellar compartment or shows only moderate suprasellar extension, dural invasion may not yet have developed and conditions for complete selective adenomectomy are improved.     

Application of low-field intraoperative magnetic resonance imaging in transsphenoidal surgery for pituitary adenomas: technical points to improve the visibility of the tumor resection margin

Background

Intraoperative magnetic resonance imaging (iMRI) is proven to be advantageous in transsphenoidal surgery (TSS) for pituitary adenomas. We evaluated the efficacy of low-field iMRI. Also, we described several techniques to enhance the visibility of the tumor resection margin.

Methods

Two hundred twenty-nine patients who underwent TSS using low-field iMRI were analyzed. iMRI was acquired in cases where the tumor removal was thought to meet the surgical goal after the tumor resection cavity had been packed with contrast-soaked cotton pledgets to improve the visibility of the tumor resection margin. Suspicious remnants were localized and explored using updated iMRI-based semi-real-time navigation. A merging technique was adopted for very small tumors. The final outcome was evaluated using postoperative 3-T diagnostic magnetic resonance imaging (MRI).

Results

Among 198 patients in whom total resection was attempted, total resection seemed to have been achieved in 184 patients based on iMRI findings. However, immediate postoperative MRI revealed remnant tumors in 4 out of 184 patients (false-negative rate, 2.2 %). The other 31 patients underwent intended subtotal resection of the tumors. Overall, in 47 patients (20.5 %), the use of iMRI led to further resection. Those patients benefited from the use of iMRI to achieve the planned extent of tumor resection.

Conclusions

iMRI maximizes the extent of resection and minimizes the possibility of unexpected tumor remnants in TSS for pituitary adenomas. It is essential to reduce imaging artifacts and enhance the visibility of the tumor resection margin during the use of low-field iMRI.     

Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma

OBJECT: Thyrotropin-secreting pituitary adenomas are rare lesions of the endocrinological system. Although introduction of a hypersensitive radioimmunoassay for thyrotropin enables the recognition of inappropriate secretion of this hormone, the aforementioned lesions remain uncommon and unfamiliar to most neurosurgeons. It has been reported previously that surgical cure of thyrotropin-secreting adenomas is more difficult than in other functional adenomas because of the large size and invasive features of the former. However, the long-term outcome after surgery has not been well documented. The authors report on a surgical series of 16 patients with thyrotropin adenoma and the results of long-term follow up. METHODS: Sixteen patients ages 23 to 62 years (12 women and four men) underwent transsphenoidal removal of thyrotropin adenomas between 1983 and 1999. These patients had the syndrome of inappropriate thyrotropin secretion (SITS) with pituitary mass lesions. Four of the patients had undergone previous subtotal thyroidectomy and/or radioiodine thyroid ablation, and 11 had been treated with antithyroid medication. Radiological investigations demonstrated macroadenomas in 14 patients, and 10 of those had cavernous sinus invasion. Surgical findings showed unusually fibrous and firm tumors in 13 (81.2%) of 16 patients. Preoperative octreotide administration was revealed to be effective for serum thyrotropin reduction as well as tumor shrinkage. Transsphenoidal surgery was performed with no morbidity resulting. Surgical remission was achieved in 10 (62.5%) of 16 patients, and total remission was achieved in 14 patients (87.5%) with a combination of additional radiation or medical therapy. In the other two patients, SITS persisted because of tumor rests in the cavernous sinus. Therefore, radiation and/or antithyroid therapy was administered. In the mean follow-up period of 7.5 years (range 11 months-15.8 years), no recurrence of tumor was observed on magnetic resonance images, whereas recurrence of SITS was found in two patients with no tumor regrowth. In addition, coexistent primary hyperthyroidism was found in two other patients despite remission of SITS after surgery. CONCLUSIONS: Transsphenoidal surgery can achieve a good long-term outcome in patients with thyrotropin-secreting pituitary adenomas if surgery is performed before these become larger, invasive tumors. In the authors' experience, thyrotropin-secreting adenomas are fibrous and firm, which makes it difficult to achieve surgical remission. In addition, even satisfactory resection of the tumor sometimes results in recurrence of SITS or hyperthyroid symptoms due to coexistent primary hyperthyroidism. It is emphasized that a careful follow-up review is necessary after surgery, especially in patients with a long preoperative history of hyperthyroidism.     

Corticotroph microadenomas of the pituitary stalk. Diagnostic and therapeutic difficulties

Thirteen percent of the pituitary adenomas in our series have been corticotroph adenomas. Most have been microadenomas located in the adenohypophysis, more often laterally than posteromedially. In a few rare cases, the corticotroph cells of the pars tuberalis gave rise to an adenoma. Only 16 cases of pituitary stalk adenomas have been published to date. We report here three new cases among a series of 150 patients who underwent surgery for corticotroph adenomas (2% incidence as in the literature). There was no difference in the clinical or biological presentation of intrasellar and pituitary stalk adenomas. This location must be systematically searched on the MRI, but a negative exploration cannot excluded the diagnosis of pituitary stalk adenoma like in intrasellar ones. Two anatomical entities seems to be separated. Some stalk adenomas developed preferentially in the supradiaphragmatic space (one in our series) and are accessible for selective resection. Others develop within the pituitary stalk itself and sometimes in the pars distalis (two patients in our series) which requires section of the pituitary stalk with hypophysectomy if the lower limit is not clearly seen during surgery. The subfrontal or pterional access is the approach of choice for suprasellar tumors. These approaches remain controversial for pituitary stalk adenomas because of the poor visibility of the pituitary stalk and the floor of the third ventricle. The transnasosphenoidal approach with extension to the sphenoidal planum and opening of the optochiasmatic cisterna appears to be the best alternative for surgical removal of these adenomas.     

Résultats comparés de la chirurgie endoscopique et de la microchirurgie dans une série consécutive de macroadénomes hypophysaires non fonctionnels

Microsurgical removal of nonfunctioning pituitary adenomas (NFPAs) is often subtotal. Removing the blind spots as viewed through the microscope, endoscopic surgery may improve the quality of removal. Our purpose was to compare the results of the two techniques in a series of NFPA patients operated on by a single surgeon. Thirty-six patients with newly diagnosed NFPAs were operated on using a purely endoscopic procedure and 29 with a microsurgical technique. All patients were explored pre- and postoperatively (at 3 and 6 months and then every 12 months) by endocrine assays, ophthalmologic exam, and 3D MRI. The endocrine and ophthalmologic results as well as the quality of resection and the complications from the two techniques were compared. The follow-up duration and the mean tumor volume (higher in the microsurgical group) were the only differences observed between the two groups. Tumor height and the invasion of the cavernous sinus were not different. All patients with preoperative visual impairment in the endoscopic group improved, whereas in the microsurgical group 90.9% improved, 4.5% were stabilized, and 4.5% worsened (p = ns). Regarding anterior pituitary functions, 42.8% of the patients improved in the endoscopic group, 45.7% remained stable, and 11.4% worsened compared to, respectively, 31, 44,8, and 24.1% in the microsurgical group (p = ns). Gross total removal was achieved in 86.1% for the endoscopic group and in only 65.5% for the microsurgical group (p = 0.075). Morbidity was similar in the two groups. This retrospective series showed that endoscopic surgery compared to microsurgery increases the quality of NFPA removal with similar morbidity.