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Sven Berkmann, Sven Schlaffer and Michael Buchfelder

Object

Volume reduction of nonfunctioning pituitary adenomas has been described, for example, after radiotherapy and pituitary tumor apoplexy. Even when considerable remnants remain after surgery, spontaneous shrinkage and relief of mass lesion symptoms can sometimes occur. The aim of this study was to assess shrinkage of tumor residues after transsphenoidal surgery and to identify predictors of tumor shrinkage.

Methods

A total of 140 patients with postoperative remnants of nonfunctioning pituitary adenomas treated at the Department of Neurosurgery, University Hospital Erlangen, Erlangen, Germany, were included in this study. All patients underwent transsphenoidal procedures with guidance by 1.5-T intraoperative MRI. The intraoperative images of remnants were compared with images taken at 3 months and at 1 year after surgery. The possible predictors analyzed were age; sex; preoperative and intraoperative tumor dimensions; tumor growth pattern; endocrinological, ophthalmological, and histological characteristics; and history of previous pituitary surgery. For statistical analyses, the Fisher's exact test, Mann-Whitney U-test, and multivariate regression table analysis were used.

Results

Follow-up imaging 3 months after surgery showed tumor remnant shrinkage of 0.5 ± 0.6 cm3 for 70 (50%) patients. This reduction was 89% ± 20% of the residual volume depicted by intraoperative MRI. In 45 (64%) patients, the remnants disappeared completely. Age, sex, and preoperative tumor volume did not significantly differ between the shrinkage and no-shrinkage groups. Positive predictors for postoperative shrinkage were cystic tumor growth (p = 0.02), additional resection of tumor remnants guided by intraoperative MRI (p = 0.04), smaller tumor volume (p = 0.04), and smaller craniocaudal tumor diameter of remnants (p = 0.0014). Negative predictors were growth into the cavernous sinus (p = 0.009), history of previous pituitary surgery (p = 0.0006) and tumor recurrence (p = 0.04), and preoperative panhypopituitarism (p = 0.04). Multivariate regression analysis indicated a positive correlation between tumor shrinkage and smaller tumor remnants (p < 0.0001) and no history of previous pituitary surgery (p = 0.003). No spontaneous change in tumor remnant volume was detected between 3 months and 1 year postoperatively. During a mean follow-up time of 2.7 years, 1 (2%) patient with postoperative tumor shrinkage had to undergo another operation because of tumor progression.

Conclusions

Spontaneous volume reduction of nonfunctioning pituitary adenoma remnants can occur within 3 months after surgery. Predictors of shrinkage are smaller tumor remnant volume and no history of previous pituitary surgery.

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Rudolf Fahlbusch, Michael Buchfelder and Uwe Schrell

✓ During a period of 3 years, 25 patients with intra- and extrasellar macroprolactinomas were pretreated with dopamine agonists for a period of 2 to 6½ weeks prior to transsphenoidal microsurgical tumor resection. Dopamine agonists were administered orally to 17 patients, intramuscularly to three patients, and both orally and intramuscularly to five patients. Repeated computerized tomography (CT) examinations revealed that all neoplasms except one cystic tumor were reduced in size during the course of dopamine-agonist administration. No complications attributable to medical pretreatment were observed. Tumor shrinkage increased the efficacy of surgery, especially in cases with considerable extrasellar extension of the adenomas. Within 3 months following adenomectomy, prolactin levels were adjusted to normal levels in 19 patients by additional low-dose treatment with dopamine agonists. Thin-collimation CT assessments performed at least 3 months after surgery showed no evidence of residual tumor tissue in 23 patients. It is concluded that administration of dopamine agonists for some weeks prior to surgery is a useful adjunct to transsphenoidal microsurgery for macroprolactinomas. The new injectable form of bromocriptine is particularly valuable for this purpose.

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Jürgen Honegger, Michael Buchfelder and Rudolf Fahlbusch

This study aimed to elucidate the endocrine outcome of craniopharyngioma surgery. In particular, endocrine results were analyzed in relation to the surgical approach. The study includes 161 patients who underwent pre- and postoperative endocrine assessment, 143 of whom had not previously undergone surgery.

Diabetes insipidus was the most common postoperative deficiency in both the transcranial and transsphenoidal groups. In the case of primary surgery (surgery as initial therapy), the overall percentage of patients with diabetes insipidus increased from 16.1% preoperatively to 59.4% postoperatively. After transcranial surgery, the rate of anterior pituitary deficiency also increased. However, normal preoperative anterior pituitary function was maintained in more than 50% of patients for each endocrine axis. Similar results were attained in the group of patients undergoing complete tumor removal. The best result was achieved for gonadal function: the incidence of hypogonadism increased only slightly from 77.4 to 79.8%. During transsphenoidal surgery, anterior pituitary function was generally preserved. An additional deficient axis was encountered postoperatively in only four (11.4%) of 35 primary surgery cases. Endocrine results were not inferior in patients with a ventrally displaced pituitary. This variant required midline incision of the gland for exposure of the craniopharyngioma. Panhypopituitarism was encountered in only one of eight patients in whom the pituitary stalk was partially resected because of tumor infiltration. None of the 88 patients who remained recurrence-free demonstrated endocrine deterioration during follow-up review, compared with the early postoperative assessment 3 months postsurgery. On the other hand, complete recovery of one endocrine axis was observed in nine of these patients during later follow-up evaluations. In five of them, diabetes insipidus had regressed.

The authors conclude that it is worth preserving the pituitary stalk and gland at surgery because anterior pituitary function is more often maintained than is generally believed. Postoperative diabetes insipidus must be accepted as a consequence of complete removal of the pituitary. However, pituitary function may recover and diabetes insipidus in particular may abate with time.

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Jürgen Honegger, Michael Buchfelder and Rudolf Fahlbusch

Object. This study aimed to elucidate the endocrinological outcome of craniopharyngioma surgery. In particular, endocrinological results were analyzed in relation to the surgical approach. The study includes 143 patients who underwent pre- and postoperative endocrinological assessment and who had not previously undergone surgery.

Methods. Diabetes insipidus was the most common postoperative deficiency in both the transcranial and transsphenoidal groups. The overall percentage of patients with diabetes insipidus increased from 16.1% preoperatively to 59.4% postoperatively. After transcranial surgery, the rate of anterior pituitary deficiency also increased. However, normal preoperative anterior pituitary function was maintained in more than 50% of patients for each endocrine axis. Similar results were attained in the group of patients undergoing complete tumor removal. The best result was achieved for gonadal function: the incidence of hypogonadism increased only slightly from 77.4 to 79.8%. The rate of anterior pituitary failure at presentation was much higher in the transsphenoidal than in the transcranial group. During transsphenoidal surgery, intact anterior pituitary functions were generally preserved. The rate of panhypopituitarism increased only slightly, from 40% before surgery to 42.9% after surgery. Endocrinological results were not inferior in patients with a ventrally displaced pituitary. This variant required midline incision of the gland for exposure of the craniopharyngioma. In the entire series of 143 patients the pituitary stalk was generally preserved. Postoperative panhypopituitarism was encountered in only one of eight patients in whom the pituitary stalk was partially resected because of tumor infiltration. None of the 88 patients who remained recurrence-free demonstrated endocrinological deterioration during follow-up review, compared with the early postoperative assessment 3 months postsurgery. On the other hand, complete recovery of one endocrine axis was observed in nine of these patients during later follow-up evaluations. In five of them, diabetes insipidus had regressed.

Conclusions. It is worth preserving the pituitary stalk and gland at surgery because of the definite chance that intact anterior pituitary functions can be maintained. Postoperative diabetes insipidus must be accepted as a common sequela following attempts at complete removal of the craniopharyngioma.

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Rudolf Fahlbusch, Jürgen Honegger, Werner Paulus, Walter Huk and Michael Buchfelder

Object. The goal of this study was to assess the outcome of surgical management in 168 consecutive patients harboring craniopharyngiomas treated between January 1983 and April 1997.

Methods. In 148 patients undergoing initial (primary) surgery, the pterional approach was most frequently used (39.2%), followed by the transsphenoidal approach (23.6%). For large retrochiasmatic craniopharyngiomas, the bifrontal interhemispheric approach was used increasingly over the pterional approach and led to improved surgical results. Total tumor removal was accomplished in 45.7% of transcranial and 85.7% of transsphenoidal procedures. The main reasons for incomplete removal were attachment to and/or infiltration of the hypothalamus, major calcifications, and attachment to vascular structures. The success rate in total tumor removal was inferior in the cases of tumor recurrence. The operative mortality rate in transcranial surgery was 1.1% in primary cases and 10.5% in cases of tumor recurrence. No patient died in the group that underwent transsphenoidal surgery. The rate of recurrence-free survival after total removal was 86.9% at 5 years and 81.3% at 10 years. In contrast, the 5-year recurrence-free survival rate was only 48.8% after subtotal removal and 41.5% after partial removal. Following primary surgery, the actuarial survival rate was 92.7% at 10 years, with the best results after complete tumor removal. At last follow up, 117 (79%) of 148 patients who underwent primary surgery were independent and without impairment.

Conclusions. Total tumor removal while avoiding hazardous intraoperative manipulation provides favorable early results and a high rate of long-term control in craniopharyngiomas.

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Rudolf Fahlbusch, Jürgen Honegger, Werner Paulus, Walter Huk and Michael Buchfelder

The surgical management of 168 consecutive patients harboring craniopharyngiomas treated between January 1983 and April 1997 is described. In 148 patients undergoing initial (primary) surgery, the pterional approach was most frequently used (39.2%) followed by the transsphenoidal approach (23.6%). For large retrochiasmatic craniopharyngiomas, the bifrontal interhemispheric approach was used increasingly over the pterional approach and led to improved surgical results. Total tumor removal was accomplished in 45.7% of transcranial and 85.7% of transsphenoidal procedures. The main reasons for incomplete removal were attachment and/or infiltration of the hypothalamus, major calcifications, and attachment to vascular structures. The success rate in total tumor removal was inferior in the cases of tumor recurrence. The operative mortality rate in transcranial surgery was 1.1% in primary cases and 10.5% in cases of tumor recurrence. No patient died in the group undergoing transsphenoidal surgery. The rate of recurrence-free survival after total removal was 86.9% at 5 years and 81.3% at 10 years. In contrast, the 5-year recurrence-free survival rate was only 48.8% after subtotal removal and 41.5% after partial removal. Following primary surgery, the actuarial survival rate was 92.7% at 10 years, with the best results after complete tumor removal. At last follow up, 117 (79%) of 148 patients who underwent primary surgery were independent and without impairment.

Total tumor removal while avoiding hazardous intraoperative manipulation provides favorable early results and a high rate of long-term control in craniopharyngiomas.

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Rudolf Fahlbusch, Oliver Ganslandt, Michael Buchfelder, Werner Schott and Christopher Nimsky

Object. The aim of this study was to evaluate whether intraoperative magnetic resonance (MR) imaging can increase the efficacy of transsphenoidal microsurgery, primarily in non—hormone-secreting intra- and suprasellar pituitary macroadenomas.

Methods. Intraoperative imaging was performed using a 0.2-tesla MR imager, which was located in a specially designed operating room. The patient was placed supine on the sliding table of the MR imager, with the head placed near the 5-gauss line. A standard flexible coil was placed around the patient's forehead. Microsurgery was performed using MR-compatible instruments. Image acquisition was started after the sliding table had been moved into the center of the magnet. Coronal and sagittal T1-weighted images each required over 8 minutes to acquire, and T2-weighted images were obtained optionally. To assess the reliability of intraoperative evaluation of tumor resection, the intraoperative findings were compared with those on conventional postoperative 1.5-tesla MR images, which were obtained 2 to 3 months after surgery.

Among 44 patients with large intra- and suprasellar pituitary adenomas that were mainly hormonally inactive, intraoperative MR imaging allowed an ultra-early evaluation of tumor resection in 73% of cases; such an evaluation is normally only possible 2 to 3 months after surgery. A second intraoperative examination of 24 patients for suspected tumor remnants led to additional resection in 15 patients (34%).

Conclusions. Intraoperative MR imaging undoubtedly offers the option of a second look within the same surgical procedure, if incomplete tumor resection is suspected. Thus, the rate of procedures during which complete tumor removal is achieved can be improved. Furthermore, additional treatments for those patients in whom tumor removal was incomplete can be planned at an early stage, namely just after surgery.

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Kalman Kovacs, Lucia Stefaneanu, Eva Horvath, Michael Buchfelder, Rudolph Fahlbusch and Wolfgang Becker

✓ A 14-year-old girl presented with a rapidly growing, invasive prolactin-producing pituitary tumor that failed to respond to dopamine agonist medication. Histological, immunocytochemical, and ultrastructural studies of the surgically removed tissue revealed a pleomorphic, chromophobic, or slightly acidophilic pituitary tumor that was immunoreactive for prolactin and that, according to electron microscopy, consisted of atypical lactotrophs showing no evidence of cell shrinkage.In situ hybridization demonstrated large amounts of prolactin messenger ribonucleic acid (mRNA), moderate amounts of estrogen receptor mRNA and dopamine (D2) receptor mRNA, and an absence of growth hormone mRNA in the tumor cells. Because D2 receptor mRNA was present in the tumor, causes other than D2 receptor loss may have been responsible for the resistance of the lactotrophs to dopamine agonist administration.

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Laszlo Barany, Cintia Meszaros, Oliver Ganslandt, Michael Buchfelder and Peter Kurucz

OBJECTIVE

The septum pellucidum is a bilateral thin membranous structure representing the border between the frontal horns of the lateral ventricles. Its most examined components are the septal veins due to their surgical importance during endoscopic septum pellucidotomy (ESP), which is a well-accepted method for surgical treatment of unilateral hydrocephalus. It is widely accepted that the septum pellucidum contains nerve fibers as well, but interestingly, no anatomical study has been addressed to its neural components before. The aim of the present study was to identify these elements as well as their relations to the septal veins and to define major landmarks within the ventricular system for neurosurgical use.

METHODS

Nine formalin-fixed human cadaveric brains (18 septa pellucida) were involved in this study. A central block containing both septa pellucida was removed and frozen at −30°C for 2 weeks in 7 cases. The fibers of the septum pellucidum and the adjacent areas including the venous elements were dissected under magnification by using homemade wooden spatulas and microsurgical instruments. In 2 cases a histological technique was used to validate the findings of the dissections. The blocks were sliced, embedded in paraffin, cut in 7-µm-thick slices, and then stained as follows: 1) with H & E, 2) with Luxol fast blue combined with cresyl violet, and 3) with Luxol fast blue combined with Sirius red.

RESULTS

The septum pellucidum and the subjacent septum verum form the medial wall of the frontal horn of the lateral ventricle. Both structures contain nerve fibers that were organized in 3 groups: 1) the precommissural fibers of the fornix; 2) the inferior fascicle; and 3) the superior fascicle of the septum pellucidum. The area directly rostral to the postcommissural column of the fornix consisted of macroscopically identifiable gray matter corresponding to the septal nuclei. The histological examinations validated the findings of the authors’ fiber dissections.

CONCLUSIONS

The nerve elements of the septum pellucidum as well as the subjacent septum verum were identified with fiber dissection and verified with histology for the first time. The septal nuclei located just anterior to the fornix and the precommissural fibers of the fornix should be preserved during ESP. Considering the venous anatomy as well as the neural architecture of the septum pellucidum, the fenestration should ideally be placed above the superior edge of the fornix and preferably dorsal to the interventricular foramen.

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Sven Berkmann, Sven Schlaffer, Christopher Nimsky, Rudolf Fahlbusch and Michael Buchfelder

Object

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods

Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results

Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions

The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.