Original Research Paper
Multi-slice computed tomography-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma: a comparison with conventional microscopic transsphenoidal surgery Masahiko Tosaka1, Tomohito Nagaki1, Fumiaki Honda1, Katsumasa Takahashi2, Yuhei Yoshimoto1 1
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Japan, 2Department of Otolaryngology – Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan
Objectives: Intraoperative computed tomography (iCT) is a reliable method for the detection of residual tumour, but previous single-slice low-resolution computed tomography (CT) without coronal or sagittal reconstructions was not of adequate quality for clinical use. The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma. Methods: This retrospective study included 30 consecutive patients with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT (eTSSziCT group), and control 30 consecutive patients who underwent conventional endoscope-assisted transsphenoidal surgery (cTSS group). The tumour volume was calculated by multiplying the tumour area by the slice thickness. Visual acuity and visual field were estimated by the visual impairment score (VIS). Results: The resection extent, (preoperative tumour volume – postoperative residual tumour volume)/ preoperative tumour volume, was 98.9% (median) in the eTSSziCT group and 91.7% in the cTSS group, and had significant difference between the groups (P50.04). Greater than 95 and w90% removal rates were significantly higher in the eTSSziCT group than in the cTSS group (P50.02 and P50.001, respectively). However, improvement in VIS showed no significant difference between the groups. The rate of complications also showed no significant difference. Discussion: Multi-slice iCT-assisted endoscopic transsphenoidal surgery may improve the resection extent of pituitary macroadenoma. Multi-slice iCT may have advantages over intraoperative magnetic resonance imaging in less expensive, short acquisition time, and that special protection against magnetic fields is not needed. Keywords: Pituitary adenoma, Transsphenoidal surgery, Endoscopy, Intraoperative computed tomography
Introduction Transsphenoidal surgery is a well-established, safe method for the treatment of pituitary adenomas that has been continuously improved over the last 20 years.1 This approach allows resection of a relatively large tumour through a small corridor incorporating the nasal passages and cavities. Several imaging modalities have been used to assist in intraoperative navigation and assessment of the extent of resection during
Correspondence to: Masahiko Tosaka, Department of Neurosurgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: [email protected]
ß W. S. Maney & Son Ltd 2015 DOI 10.1179/1743132815Y.0000000078
transsphenoidal surgery for pituitary adenomas. X-ray fluoroscopy was the first intraoperative imaging modality introduced during transsphenoidal surgery,2 which improved the method, but could not evaluate the extent of tumour resection. The pituitary gland of the hypophysis is a small organ, which is located deep in the brain and is surrounded by bone, so high-resolution imaging is required to accurately evaluate any tumour remnant. Diagnostic computer-aided imaging, such as computed tomography (CT), or magnetic resonance (MR) imaging, can evaluate exact tumour volume, and is very useful in transsphenoidal surgery, which
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is intended to remove a relatively large tumour from a small window.3 Intraoperative CT (iCT) was found to reliably detect residual tumour in the early 1990s,4,5 but single-slice, low-resolution CT with coronal or sagittal reconstruction was not of adequate quality for clinical use. Therefore, MR imaging developed at the same time became the leading method,6 and continues to be a diagnostic technique for transsphenoidal surgery. However, the next generation of CT scanners offers multi-slice, highspeed, high-resolution imaging with multiplanar reconstructions including the axial, sagittal, and coronal planes.7,8 Intraoperative computed tomography has been most extensively described for use in spinal surgery, because CT has advantages for evaluation of bone tissue compared to MR imaging. Recently, the usefulness in the skull base surgery has also been pointed out.9 The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma.
Methods Patients This retrospective study included a series of 30 consecutive patients, 16 females and 14 males aged 16–81 (51.5 + 27.0) years, with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT between July 2010 and April 2013 (eTSSziCT group), and a series of 30 consecutive patients, 17 females and 13 males aged 29–75 (52.5 + 19.0) years who underwent cTSS from October 2003 to May 2007 (cTSS group). All surgeries in the eTSSziCT group and cTSS group were performed by the same surgeon (MT) at a teaching and tertiary care hospital, which is a major referral site for patients with pituitary adenoma. The temporary suspension from April 2007 to October 2009 was caused by temporary transfer to another institution of the surgeon (MT), who specialises in pituitary surgery. Intraoperative computed tomography was utilised in the cTSS group for about 1 year after November 2009. However, different combinations, including cTSS with iCT, cTSS without iCT, and eTSS without iCT, were randomly used in this period, so these cases were excluded based on the need for consecutive strategy. Therefore, the present series of 30 cases was started at our first eTSS with iCT. These two series both included consecutive cases of macroadenoma, including recurrent tumours, cases with severe invasion of the cavernous sinus (Knosp Grade 3 or 4), and cases of giant (w4 cm) adenoma. This study was reviewed and approved by the institutional review board.
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Surgical procedure Under general anaesthesia with tracheal intubation, the patient was placed supine with the head placed on a radiolucent headrest. The reference arc of the navigation system was fixed on the forehead with a head band (StealthStation; Medtronic Sofamor Danek, Memphis, TN, USA) for image-guided surgery. A 4-mm rigid endoscope with a 0˚, 30˚, or 70˚ angled lens (Karl Storz GmbH & Co. KG, Tuttlingen, Germany) was combined with a high-vision camera and video system (FlexVision U-500; Stryker Endoscopy, San Jose, CA, USA). Intraoperative radiography was routinely used for realtime confirmation of the operative site in the sagittal plane. The endoscope was introduced through either the right or left nostril (single nostril method) during the period of this study. The endoscope was sometimes held with the three hands technique during intrasellar and suprasellar procedures after nasal introduction. The floor of the sella was opened with a high-speed drill and a Kerrison punch. The dura was opened, then the adenoma was identified and removed in the standard fashion, by suction, or using forceps or curette. Intraoperative imaging was either performed when the surgeon had the impression of total removal or, in the case of subtotal or partial removal, when the surgeon thought that no further removal was possible by the approach. Prior to intraoperative imaging, a small abdominal fat graft was harvested, and temporarily inserted in the space in the sella to clarify the extent of resection on iCT (Figs. 1 and 2). The surgical site was then covered with a drape and the table was manoeuvred into eight-slice configuration multislice CT scanner (Somatom Emotion; Siemens, Erlangen, Germany). Computed tomography was performed with 1- or 2-mm table feed, 130 kV, 345 mA, and field of view 500 mm to obtain 1- or 2-mm thick axial slices. The data acquired in the axial plane was reformatted into two-dimensional coronal, sagittal, and axial planes. The total duration from the decision for iCT to restarting the next surgical procedure was about 7–9 minutes (491.5+ 95 second, n56). If complete removal was achieved, the surgery was finished. If insufficient removal was judged, second look removal, and further iCT were attempted. By contrast, conventional transsphenoidal surgery (cTSS) was performed mainly under the operating microscope with endoscope assistance. Intraoperative radiography was routinely used, but not for computer-assisted navigation systems. All procedures were performed through the endonasal transsphenoidal route. The adenoma was removed with curettage and suction under the operating microscope. At the end of removal, the endoscope was used to confirm the extent of removal, and further removal was rarely performed.
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Figure 1 Representative case of intraoperative evaluation of total removal by intraoperative computed tomography (iCT) in a 22-year-old female. Preoperative coronal (A) and sagittal (D) T1-weighted MR images with contrast medium. Coronal (B) and sagittal (E) reconstructed iCT images (from 2-mm thickness axial data) demonstrating the pituitary stalk and gland without residual tumour. Postoperative coronal (C) and sagittal (F) MR images demonstrating no residual tumour. This case was finally evaluated as >95% removal.
Radiological evaluation of tumour removal The extent of tumour removal was generally evaluated on MR imaging mainly at 1 month after surgery. T1-weighted MR images with gadolinium taken before and after surgery were used for estimation of surgical removal, with reference to T1-weighted and T2-weighted images. Slice thicknesses were 3 mm in all but one case (3.5 mm). 1.5T or 3T MR imaging systems were used. Film-based MR images were first scanned into a JPEG format and analysed, using Image J software version 1.46 (http://rsbweb.nih.gov/ij/). More recent DICOM (digital imaging and communications in medicine) imaging data were evaluated using the PACS (picture archiving and communication system) (Neovista; Konica Minolta Health Care, Tokyo, Japan). The contour of the tumour in each image was traced using freehand tools and the actual area was measured. The tumour volume was calculated by multiplying each area by the slice thickness.10 The resection extent was calculated as preoperative tumour volume postoperative residual tumour volume/preoperative tumour volume. Gross total removal (GTR) was defined as complete removal of the adenoma. w95% removal was defined as removal of w95% (95% near total removal
plus GTR), and w90% removal as removal of w90% (90% near total removal plus GTR) of the tumour.11,12
Evaluation of pre- and postoperative status Visual acuity and visual field were graded as the visual impairment score (VIS).13,14 All patients underwent a standard (or partly arranged) combined anterior pituitary function test as described previously.15 Hormone replacement following surgery was guided by the patient’s pre- and post-operative endocrine status and clinical complaints. Final need for hormone replacement, including anterior pituitary hormones, and desmopressin was evaluated as hypofunction.16 However, this outcome did not imply newly developed hypofunction after surgery because several patients had preoperative pituitary hypofunction of various grades. In the early postoperative course, serum sodium level was frequently measured for early detection of hyponatremia (v125 mEq/l).17 Postoperative diabetes insipidus was diagnosed using previously reported criteria.18
Statistical analysis Fisher’s exact test was used to compare categorical variables between the eTSSziCT and cTSS groups.
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Figure 2 Representative case of intraoperative evaluation of non-total removal by intraoperative computed tomography (iCT) in a 25-year-old male. Preoperative coronal (A) and sagittal (D) T1-weighted MR images with contrast medium. Coronal (B) and sagittal (E) reconstructed iCT images (from 1-mm thickness axial data) demonstrating small remnant tumour. However, the remnant tumour was too hard to be sufficiently removed at second look. Postoperative coronal (C) and sagittal (F) MR images demonstrating small residual tumour. This case was finally evaluated as >90% removal.
All continuous variables were expressed as median + interquartile range. The Wilcoxon rank-sum test was used to compare continuous variables between the eTSSziCT and cTSS groups. A value of Pv0.05 was considered to be statistically significant.
Results The median height of the pituitary adenoma from the sella turcica floor was 28.4+ 9.0 mm in the eTSSziCT group and 25.9+ 6.7 mm in the cTSS group. Recurrent cases were found in six (20%) cases in the eTSSziCT group and five (16.7%) in the cTSS group. Lateral extension of the tumour was estimated by Knosp grading score. If the grading was different between both sides for any patient, the tumour was classified according to the higher grade. Knosp Grades 3–4 (high grades) were found in eight (26.7%) cases in the eTSSziCT group and seven cases (23.3%) in the cTSS group. No significant intergroup differences were found in age, sex, height of adenoma, rate of recurrence, and rate of high Knosp grades (Table 1).
Intraoperative evaluations by iCT First iCT imaging detected no tumour remnant in 15 (50.0%) patients. First intraoperative imaging depicted remnant tumour in 15 patients, nine of whom underwent
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extended resection. The other six (20.0%) cases were judged with no need of further resection, including cases not planned primarily for total resection due to Knosp grade 4 cavernous sinus invasion, and two cases with remnant hard tumour which was easy to bleed. In nine (30%) patients, who received second look resection, final complete tumour removal was confirmed in six (20.0%) patients on final iCT, whereas further resection in the second look procedure was stopped in the other three (10.0%) patients because of hard remnant tumour or easy bleeding. The rate of complete tumour removal was increased from 50.0 (15/30 cases) to 70.0% (21/30) by second look resection after iCT. The intraoperative evaluation of complete removal by iCT was closer to the finding of w95% removal rate than the GTR rate, and the w90% removal rate shown by postoperative MR imaging.
Radiological results The surgical results based on radiological examination are summarised in Table 1. The resection extent, (preoperative tumour volume – postoperative residual tumour volume)/preoperative tumour volume, was 98.9+ 5.0% in the eTSSziCT group and 91.7+ 22.2% in the cTSS group. No significant difference was seen in preoperative tumour and postoperative residual tumour volumes between the groups.
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Table 1 Results of resection between endoscopic transsphenoidal surgery using iCT (eTSSziCT) and conventional endoscope-assisted transsphenoidal surgery (cTSS) for pituitary macroadenomas
Number of cases Age, years Sex, m:f Height, mm Recurrence rate,% (n) Knosp 3–4,% (n) Initial volume, mm3 Residual volume, mm3 Resection extent,% GTR,% (n) .95% removal,% (n) .90% removal,% (n)
Total
eTSS þ iCT
cTSS
P value†
60 52.0^16.5 27:33 27.1 ^ 7.9 18.3 (11/60) 25.0 (15/60) 8805 ^ 8071 393.5 ^ 1118.5 96.9 ^ 13.5 45.0 (27/60) 60.0 (36/60) 73.3 (44/60)
30 51.5 ^ 27.0 14:16 28.4 ^ 9.0 20 (6/30) 26.7 (8/30) 10 124 ^ 8296 110.0 ^ 767.0 98.9 ^ 5.0 50.0 (15/30) 76.7 (23/30) 93.3 (28/30)
30 52.5 ^ 19.0 13:17 25.9 ^ 6.7 16.7 (5/30) 23.3 (7/30) 7964 ^ 7108 901.5 ^ 1818.0 91.7 ^ 22.2 40.0 (12/30) 43.3 (13/30) 53.3 (16/30)
0.04* 0.02* 0.001**
Note: * P,0.05, ** P,0.005. †Data are shown only in statistically significant case.
However, the resection extent was significantly higher in the eTSSziCT group than in the cTSS group (P50.04). There was no significant difference in GTR rate, but both w95% removal and w90% removal rates were significantly higher in the eTSSziCT group than in the cTSS group (P50.02 and P50.001, respectively). Additionally, we compared the results of the cTSS group (n530) with the eTSSziCT group excluding patients who did not undergo second look resection (n521). No significant difference was seen in resection extent (100+ 6.5%), GTR rate (52.4%, 11/21), and w95% removal rate (71.4%, 15/21). However, w90% removal rate (90.5%, 19/21) was significantly higher in the eTSSziCT group excluding second look resection than in the cTSS group (P50.006).
Table 2 Postoperative complications between endoscopic transsphenoidal surgery using iCT (eTSSziCT) and conventional endoscope-assisted transsphenoidal surgery (cTSS) for pituitary macroadenomas
Number of cases Transient DI Transient hyponatremia Hormone replacement* CSF leakage Postoperative haemorrage
Total
eTSS þ iCT
cTSS
60 17 (1†) 5 6 (1‡) 2 1
30 8 (1†) 2 3 (1‡) 2 0
30 9 3 3 0 1
Note: *Anterior pituitary hormones. †Permanent DI. ‡Preoperative normal pituitary function case. Other five cases had anterior pituitary dysfunction before operation.
performed on the day after first operation, and visual acuity was recovered fully.
Other results and complications A total 58 of cases (97%) were used for analysis because one case in each group was not available. The median preoperative VIS was 12 + 22.8 in the eTSSziCT group and 14+ 21.5 in the cTSS group. The median postoperative VIS was 2+ 8.5 in the eTSSziCT group and 0+ 4.5 in the cTSS group. The median improvement score (postoperative VIS – preoperative VIS) was 10+ 17.5 in the eTSSziCT group and 6+ 20 in the cTSS group. No significant differences between eTSSziCT group and cTSS group were found in preoperative VIS, postoperative VIS, and improvement score.14 The postoperative complications are summarised in Table 2. Postoperative hormone replacement therapy due to anterior pituitary hormone deficiency was needed in three patients in the eTSSziCT group and three patients in the cTSS group. Only one of these patients (eTSSziCT group) had preoperative normal pituitary function. Postoperative cerebrospinal fluid (CSF) leakage required re-operation in two patients in the eTSSziCT group. Postoperative deterioration of visual acuity due to postoperative haemorrage from the residual tumour occurred in one case in the cTSS group. The re-operation was
Discussion Intraoperative MR (iMR) imaging has recently been combined with cTSS.19–21 Intraoperative MR imaging is considered to be a useful method to detect remnant tumour in the dead angle portion of the operating microscope. However, eTSS has recently become the standard technique, replacing cTSS, so that iMR imaging is likely to be used in eTSS, resulting in improved tumour removal rate.22,23 However, MR imaging requires a special operating room, and the imaging time is quite long. Intraoperative computed tomography has advantages over iMR imaging in these areas, as special protection against magnetic fields is not needed, and the scanner is less expensive and less complex. Intraoperative computed tomography requires only about 8 minutes from discontinuation to resume the operative procedures. The latest multi-slice and high-resolution CT scanners allow clear reconstruction of both coronal and sagittal planes. Moreover, CT has particular advantages over MR imaging and other imaging methods in that evaluation of acute bleeding is intuitive and easy, and imaging of bone structures including
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bone shape and range of bone dissection is clearer and easier to interpret. However, the resolution of CT may be inferior compared with MR imaging for the detection of remnant pituitary tumour. In particular, iCT cannot differentiate normal pituitary tissue, and cavernous sinus invasion is not clear without contrast enhancement. The present study found that intraoperative evaluation of complete removal on iCT was almost consistent with w95% removal rate on postoperative MR imaging. This discrepancy between the findings of iCT and postoperative MR imaging requires attention. Future use of iCT may depend on improved imaging quality, including contrast enhancement. Magnetic resonance imaging has been the standard intraoperative imaging method for pituitary adenoma surgery. Introduction of the 0.2-T MR scanner increased the GTR rate from 43 to 70% or from 45 to 75%,24,25 or further from 58.2 to 83.6% or from 69 to 85%.26,27 High-resolution 1.5-T iMR imaging increased the removal rate from 41 to 67% or from 58 to 82%.26,27 Therefore, iMR imaging improves the GTR rate by about 25% (range 14–32%).25–29 However, no significant difference was seen between low-resolution and high-resolution iMR imaging. Intraoperative usage of CT for pituitary adenoma surgery has rarely been reported because of the relatively low resolution and very low flexibility of the imaging plane.5 Recently, iCT has been reconsidered because of the development of multi-slice, high-resolution CT with imaging slice flexibility, which allows accurate intraoperative evaluation.8 The GTR rate was 59% (first case of 89%) in a series of 33 transsphenoidal procedures using multi-slice iCT.8 In our series, w95% removal and w90% removal rates were 76.7 and 93.3%, respectively, after eTSS with iCT compared with 43.3 and 53.3%, respectively, after cTSS without iCT. However, no significant difference was observed in GTR rate between the eTSSziCT and cTSS groups. Recently, we have performed extracapsular dissection not only for microadenomas but also for macroadenomas,30 but our policy of resection was standard intracapsular removal in this study period. Therefore, tumour remnant of 5% or less was observed frequently, which mainly consisted of the tumour capsule. However, iCT without contrast medium cannot clearly detect very small tumour remnant of 5% or less, which may be one reason why no significant difference was found in GTR rate. The increase in w95% removal rate in the eTSSziCT group may be about 30% in this study, which is similar to previous improvements in GTR rate using iMR imaging.14,24,25 The increase in w90% removal rate in the eTSSziCT group may be about 40% in this study, as a result of the additive effect of endoscopy and iCT. In our series, GTR rate was low as 50.0% using
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eTSSziCT. This series included only macroadenoma cases, not including small adenoma without visual problems before surgery, but including cases with cavernous sinus invasion and recurrent tumour. The consecutive series of eTSSziCT group in this study included eight patients (26.7%) with Knosp Grade 3–4 tumours. Gross total removal could not be achieved in any of these cases using endoscopy and iCT. Gross total removal rate was 68% in only Knosp Grade 1–2 tumours. We sometimes consider gamma knife surgery for remnant tumour in the lateral side of the internal carotid artery, especially in recurrent cases. In this series, one recurrent case with Knosp Grade four adenoma was treated by gamma knife irradiation after eTSSziCT removal. Surgery for pituitary adenoma without intraoperative imaging results in improvement of visual acuity by 48–92%.20,31 Intraoperative MR imaging can directly demonstrate the optic nerve and decompression of the optic nerve.32 Pituitary surgery with iMR imaging has improved visual acuity by 66–100%.23,25,26,28 However, this improvement is similar to that obtained by the conventional procedure without intraoperative imaging.20 The present study found no cases of decreased VIS, but improvement in the VIS after eTSS with iCT was not significantly different from that after cTSS. Visual symptoms caused by pituitary adenoma may result from blood flow problems to the optic chiasm and ischaemia. Even if the optic chiasm is not perfectly free from compression, any visual symptoms will improve dramatically with improvement of blood flow.20,31,32 Therefore, any change in visual symptoms may only approximately reflect the extent of resection. iCT has inferior resolution for the optic nerve and chiasm compared to iMR imaging. However, iCT may not have disadvantages in the outcome of visual symptoms, as the present study found improvement in VIS consistent with previous reports.13 Endocrinological side effects, such as diabetes insipidus and hypopituitarism, showed no differences between the eTSSziCT and cTSS groups. However, postoperative CSF leakage occurred in two patients with giant adenoma (w4 cm) in the eTSSziCT group. The risk of CSF leakage is reported to be slightly higher (16.7%) in surgery for giant adenoma compared with normal adenomas.33 Wider exposure and more extensive arachnoid dissection may increase the risk. Expansion of the bone resection for an endoscope may also increase the risk.34 Nasal flap was not used in this series of cases. Reconstruction using nasal flap may be useful for high-flow CSF leakage after resection of giant adenoma.34,35
Limitations The present series of cTSS used for our control group was performed by microsurgery mainly with the
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endoscope. This operation technique was completely discontinued after the introduction of iCT because eTSS and iCT were introduced at the same time in our institution, so the technique of endoscopy may have been responsible for some of the observed improvements. This is a critical bias in this study, but was unavoidable since the endoscope and intraoperative diagnostic imaging were both introduced worldwide at this time.36 Our additional analysis compared the cTSS group with the eTSSziCT group excluding second look resection. No significant difference was seen in resection extent, GTR rate, and w95% removal rate. Introduction of endoscopy might be expected to have relatively stronger effect on the w90% removal rate, as was observed in this study. The improvement of results in the eTSSziCT group may be interpreted as the combined effect of endoscopy and iCT. Introduction of neuronavigation might also have improved resection results in several cases of the eTSSziCT group.37 Neuronavigation was introduced simultaneously with iCT and endoscopy in our institute. X-ray fluoroscopy was routinely used in all cases in the cTSS and eTSSziCT groups. We used neuronavigation only as a supplement for confirmation of the depth in the case of giant tumour. However, more frequent use of neuronavigation might be effective for resection of pituitary adenomas.38 Intraoperative MR imaging, especially combined with functional neuronavigation,26–28 allows more radical resections with lower morbidity. Intraoperative computed tomography-assisted endoscopic transsphenoidal surgery combined with neuronavigation might be less expensive and less complex, but achieve similar effectiveness.
Disclaimer Statements Contributors Conceiving and designing the study: MT, YY. Ethics approval: MT, YY. Collecting the data: MT, NT, FH. Interpreting the data: MT, NT, FH, KT Writing the article in whole or in part: MT, FH, YY. Revising the article: MT, YY, KT. Funding None. Conflicts of interest No conflicts of interest. Ethics approval This study was reviewed and approved by the institutional review board of Gunma University Graduate School of Medicine.
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24 Nimsky C, Ganslandt O, Tomandl B, Buchfelder M, Fahlbusch R. Low-field magnetic resonance imaging for intraoperative use in neurosurgery: a 5-year experience. Eur Radiol. 2002;12:2690–703. 25 Fahlbusch R, Ganslandt O, Buchfelder M, Schott W, Nimsky C. Intraoperative magnetic resonance imaging during transsphenoidal surgery. J Neurosurg. 2001;95:381–90. 26 Wu JS, Shou XF, Yao CJ, Wang YF, Zhuang DX, Mao Y, et al. Transsphenoidal pituitary macroadenomas resection guided by polestar N20 low-field intraoperative magnetic resonance imaging: comparison with early postoperative high-field magnetic resonance imaging. Neurosurgery. 2009;65:63–70. 27 Berkmann S, Fandino J, Mu¨ller B, Remonda L, Landolt H. Intraoperative MRI and endocrinological outcome of transsphenoidal surgery for non-functioning pituitary adenoma. Acta Neurochir (Wien). 2012;154:639–47. 28 Nimsky C, von Keller B, Ganslandt O, Fahlbusch R. Intraoperative high-field magnetic resonance imaging in transsphenoidal surgery of hormonally inactive pituitary macroadenomas. Neurosurgery. 2006;59:105–14. 29 Szerlip NJ, Zhang YC, Placantonakis DG, Goldman M, Colevas KB, Rubin DG, et al. Transsphenoidal resection of sellar tumors using high-field intraoperative magnetic resonance imaging. Skull Base. 2011;21:223–32. 30 Qu X, Xu G, Qu Y, Song T. The pseudocapsule surrounding a pituitary adenoma and its clinical significance. J Neurooncol. 2011;101:171–8.
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31 Jones J, Ruge J. Intraoperative magnetic resonance imaging in pituitary macroadenoma surgery: an assessment of visual outcome. Neurosurg Focus. 2007;23:E12. 32 Yoneoka Y, Hatase T, Watanabe N, Jinguji S, Okada M, Takagi M, et al. Early morphological recovery of the optic chiasm is associated with excellent visual outcome in patients with compressive chiasmal syndrome caused by pituitary tumors. Neurol Res. 2015;37:1–8. 33 Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Paluzzi A, Wang EW, Snyderman CH. Endoscopic endonasal surgery for giant pituitary adenomas: advantages and limitations. J Neurosurg. 2013;118:621–31. 34 Goudakos JK, Markou KD, Georgalas C. Endoscopic versus microscopic trans-sphenoidal pituitary surgery: a systematic review and meta-analysis. Clin Otolaryngol. 2011;36:212–20. 35 Saeki N, Horiguchi K, Murai H, Hasegawa Y, Hanazawa T, Okamoto Y. Endoscopic endonasal pituitary and skull base surgery. Neurol Med Chir (Tokyo). 2010;50:756–64. 36 Jane JA, Laws ER. Endoscopy versus MR imaging. J Neurosurg. 2010;112:734. 37 Zhang Y, Wang Z, Liu Y, Zong X, Song M, Pei A, et al. Endoscopic transsphenoidal treatment of pituitary adenomas. Neurol Res. 2008;30:581–6. 38 Carvi Y, Nievas MN, Ho¨llerhage HG. Reliability of neuronavigation-assisted trans-sphenoidal tumor resections. Neurol Res. 2007;29:557–62.
Multi-slice computed tomography-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma: a comparison with conventional microscopic transsphenoidal surgery Masahiko Tosaka1, Tomohito Nagaki1, Fumiaki Honda1, Katsumasa Takahashi2, Yuhei Yoshimoto1 1
Department of Neurosurgery, Gunma University Graduate School of Medicine, Maebashi, Japan, 2Department of Otolaryngology – Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Japan
Objectives: Intraoperative computed tomography (iCT) is a reliable method for the detection of residual tumour, but previous single-slice low-resolution computed tomography (CT) without coronal or sagittal reconstructions was not of adequate quality for clinical use. The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma. Methods: This retrospective study included 30 consecutive patients with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT (eTSSziCT group), and control 30 consecutive patients who underwent conventional endoscope-assisted transsphenoidal surgery (cTSS group). The tumour volume was calculated by multiplying the tumour area by the slice thickness. Visual acuity and visual field were estimated by the visual impairment score (VIS). Results: The resection extent, (preoperative tumour volume – postoperative residual tumour volume)/ preoperative tumour volume, was 98.9% (median) in the eTSSziCT group and 91.7% in the cTSS group, and had significant difference between the groups (P50.04). Greater than 95 and w90% removal rates were significantly higher in the eTSSziCT group than in the cTSS group (P50.02 and P50.001, respectively). However, improvement in VIS showed no significant difference between the groups. The rate of complications also showed no significant difference. Discussion: Multi-slice iCT-assisted endoscopic transsphenoidal surgery may improve the resection extent of pituitary macroadenoma. Multi-slice iCT may have advantages over intraoperative magnetic resonance imaging in less expensive, short acquisition time, and that special protection against magnetic fields is not needed. Keywords: Pituitary adenoma, Transsphenoidal surgery, Endoscopy, Intraoperative computed tomography
Introduction Transsphenoidal surgery is a well-established, safe method for the treatment of pituitary adenomas that has been continuously improved over the last 20 years.1 This approach allows resection of a relatively large tumour through a small corridor incorporating the nasal passages and cavities. Several imaging modalities have been used to assist in intraoperative navigation and assessment of the extent of resection during
Correspondence to: Masahiko Tosaka, Department of Neurosurgery, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Email: [email protected]
ß W. S. Maney & Son Ltd 2015 DOI 10.1179/1743132815Y.0000000078
transsphenoidal surgery for pituitary adenomas. X-ray fluoroscopy was the first intraoperative imaging modality introduced during transsphenoidal surgery,2 which improved the method, but could not evaluate the extent of tumour resection. The pituitary gland of the hypophysis is a small organ, which is located deep in the brain and is surrounded by bone, so high-resolution imaging is required to accurately evaluate any tumour remnant. Diagnostic computer-aided imaging, such as computed tomography (CT), or magnetic resonance (MR) imaging, can evaluate exact tumour volume, and is very useful in transsphenoidal surgery, which
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is intended to remove a relatively large tumour from a small window.3 Intraoperative CT (iCT) was found to reliably detect residual tumour in the early 1990s,4,5 but single-slice, low-resolution CT with coronal or sagittal reconstruction was not of adequate quality for clinical use. Therefore, MR imaging developed at the same time became the leading method,6 and continues to be a diagnostic technique for transsphenoidal surgery. However, the next generation of CT scanners offers multi-slice, highspeed, high-resolution imaging with multiplanar reconstructions including the axial, sagittal, and coronal planes.7,8 Intraoperative computed tomography has been most extensively described for use in spinal surgery, because CT has advantages for evaluation of bone tissue compared to MR imaging. Recently, the usefulness in the skull base surgery has also been pointed out.9 The present study evaluated the results of multi-slice iCT-assisted endoscopic transsphenoidal surgery for pituitary macroadenoma.
Methods Patients This retrospective study included a series of 30 consecutive patients, 16 females and 14 males aged 16–81 (51.5 + 27.0) years, with newly diagnosed or recurrent pituitary macroadenoma with supradiaphragmatic extension who underwent endoscopic transsphenoidal surgery using iCT between July 2010 and April 2013 (eTSSziCT group), and a series of 30 consecutive patients, 17 females and 13 males aged 29–75 (52.5 + 19.0) years who underwent cTSS from October 2003 to May 2007 (cTSS group). All surgeries in the eTSSziCT group and cTSS group were performed by the same surgeon (MT) at a teaching and tertiary care hospital, which is a major referral site for patients with pituitary adenoma. The temporary suspension from April 2007 to October 2009 was caused by temporary transfer to another institution of the surgeon (MT), who specialises in pituitary surgery. Intraoperative computed tomography was utilised in the cTSS group for about 1 year after November 2009. However, different combinations, including cTSS with iCT, cTSS without iCT, and eTSS without iCT, were randomly used in this period, so these cases were excluded based on the need for consecutive strategy. Therefore, the present series of 30 cases was started at our first eTSS with iCT. These two series both included consecutive cases of macroadenoma, including recurrent tumours, cases with severe invasion of the cavernous sinus (Knosp Grade 3 or 4), and cases of giant (w4 cm) adenoma. This study was reviewed and approved by the institutional review board.
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Surgical procedure Under general anaesthesia with tracheal intubation, the patient was placed supine with the head placed on a radiolucent headrest. The reference arc of the navigation system was fixed on the forehead with a head band (StealthStation; Medtronic Sofamor Danek, Memphis, TN, USA) for image-guided surgery. A 4-mm rigid endoscope with a 0˚, 30˚, or 70˚ angled lens (Karl Storz GmbH & Co. KG, Tuttlingen, Germany) was combined with a high-vision camera and video system (FlexVision U-500; Stryker Endoscopy, San Jose, CA, USA). Intraoperative radiography was routinely used for realtime confirmation of the operative site in the sagittal plane. The endoscope was introduced through either the right or left nostril (single nostril method) during the period of this study. The endoscope was sometimes held with the three hands technique during intrasellar and suprasellar procedures after nasal introduction. The floor of the sella was opened with a high-speed drill and a Kerrison punch. The dura was opened, then the adenoma was identified and removed in the standard fashion, by suction, or using forceps or curette. Intraoperative imaging was either performed when the surgeon had the impression of total removal or, in the case of subtotal or partial removal, when the surgeon thought that no further removal was possible by the approach. Prior to intraoperative imaging, a small abdominal fat graft was harvested, and temporarily inserted in the space in the sella to clarify the extent of resection on iCT (Figs. 1 and 2). The surgical site was then covered with a drape and the table was manoeuvred into eight-slice configuration multislice CT scanner (Somatom Emotion; Siemens, Erlangen, Germany). Computed tomography was performed with 1- or 2-mm table feed, 130 kV, 345 mA, and field of view 500 mm to obtain 1- or 2-mm thick axial slices. The data acquired in the axial plane was reformatted into two-dimensional coronal, sagittal, and axial planes. The total duration from the decision for iCT to restarting the next surgical procedure was about 7–9 minutes (491.5+ 95 second, n56). If complete removal was achieved, the surgery was finished. If insufficient removal was judged, second look removal, and further iCT were attempted. By contrast, conventional transsphenoidal surgery (cTSS) was performed mainly under the operating microscope with endoscope assistance. Intraoperative radiography was routinely used, but not for computer-assisted navigation systems. All procedures were performed through the endonasal transsphenoidal route. The adenoma was removed with curettage and suction under the operating microscope. At the end of removal, the endoscope was used to confirm the extent of removal, and further removal was rarely performed.
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Figure 1 Representative case of intraoperative evaluation of total removal by intraoperative computed tomography (iCT) in a 22-year-old female. Preoperative coronal (A) and sagittal (D) T1-weighted MR images with contrast medium. Coronal (B) and sagittal (E) reconstructed iCT images (from 2-mm thickness axial data) demonstrating the pituitary stalk and gland without residual tumour. Postoperative coronal (C) and sagittal (F) MR images demonstrating no residual tumour. This case was finally evaluated as >95% removal.
Radiological evaluation of tumour removal The extent of tumour removal was generally evaluated on MR imaging mainly at 1 month after surgery. T1-weighted MR images with gadolinium taken before and after surgery were used for estimation of surgical removal, with reference to T1-weighted and T2-weighted images. Slice thicknesses were 3 mm in all but one case (3.5 mm). 1.5T or 3T MR imaging systems were used. Film-based MR images were first scanned into a JPEG format and analysed, using Image J software version 1.46 (http://rsbweb.nih.gov/ij/). More recent DICOM (digital imaging and communications in medicine) imaging data were evaluated using the PACS (picture archiving and communication system) (Neovista; Konica Minolta Health Care, Tokyo, Japan). The contour of the tumour in each image was traced using freehand tools and the actual area was measured. The tumour volume was calculated by multiplying each area by the slice thickness.10 The resection extent was calculated as preoperative tumour volume postoperative residual tumour volume/preoperative tumour volume. Gross total removal (GTR) was defined as complete removal of the adenoma. w95% removal was defined as removal of w95% (95% near total removal
plus GTR), and w90% removal as removal of w90% (90% near total removal plus GTR) of the tumour.11,12
Evaluation of pre- and postoperative status Visual acuity and visual field were graded as the visual impairment score (VIS).13,14 All patients underwent a standard (or partly arranged) combined anterior pituitary function test as described previously.15 Hormone replacement following surgery was guided by the patient’s pre- and post-operative endocrine status and clinical complaints. Final need for hormone replacement, including anterior pituitary hormones, and desmopressin was evaluated as hypofunction.16 However, this outcome did not imply newly developed hypofunction after surgery because several patients had preoperative pituitary hypofunction of various grades. In the early postoperative course, serum sodium level was frequently measured for early detection of hyponatremia (v125 mEq/l).17 Postoperative diabetes insipidus was diagnosed using previously reported criteria.18
Statistical analysis Fisher’s exact test was used to compare categorical variables between the eTSSziCT and cTSS groups.
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Figure 2 Representative case of intraoperative evaluation of non-total removal by intraoperative computed tomography (iCT) in a 25-year-old male. Preoperative coronal (A) and sagittal (D) T1-weighted MR images with contrast medium. Coronal (B) and sagittal (E) reconstructed iCT images (from 1-mm thickness axial data) demonstrating small remnant tumour. However, the remnant tumour was too hard to be sufficiently removed at second look. Postoperative coronal (C) and sagittal (F) MR images demonstrating small residual tumour. This case was finally evaluated as >90% removal.
All continuous variables were expressed as median + interquartile range. The Wilcoxon rank-sum test was used to compare continuous variables between the eTSSziCT and cTSS groups. A value of Pv0.05 was considered to be statistically significant.
Results The median height of the pituitary adenoma from the sella turcica floor was 28.4+ 9.0 mm in the eTSSziCT group and 25.9+ 6.7 mm in the cTSS group. Recurrent cases were found in six (20%) cases in the eTSSziCT group and five (16.7%) in the cTSS group. Lateral extension of the tumour was estimated by Knosp grading score. If the grading was different between both sides for any patient, the tumour was classified according to the higher grade. Knosp Grades 3–4 (high grades) were found in eight (26.7%) cases in the eTSSziCT group and seven cases (23.3%) in the cTSS group. No significant intergroup differences were found in age, sex, height of adenoma, rate of recurrence, and rate of high Knosp grades (Table 1).
Intraoperative evaluations by iCT First iCT imaging detected no tumour remnant in 15 (50.0%) patients. First intraoperative imaging depicted remnant tumour in 15 patients, nine of whom underwent
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extended resection. The other six (20.0%) cases were judged with no need of further resection, including cases not planned primarily for total resection due to Knosp grade 4 cavernous sinus invasion, and two cases with remnant hard tumour which was easy to bleed. In nine (30%) patients, who received second look resection, final complete tumour removal was confirmed in six (20.0%) patients on final iCT, whereas further resection in the second look procedure was stopped in the other three (10.0%) patients because of hard remnant tumour or easy bleeding. The rate of complete tumour removal was increased from 50.0 (15/30 cases) to 70.0% (21/30) by second look resection after iCT. The intraoperative evaluation of complete removal by iCT was closer to the finding of w95% removal rate than the GTR rate, and the w90% removal rate shown by postoperative MR imaging.
Radiological results The surgical results based on radiological examination are summarised in Table 1. The resection extent, (preoperative tumour volume – postoperative residual tumour volume)/preoperative tumour volume, was 98.9+ 5.0% in the eTSSziCT group and 91.7+ 22.2% in the cTSS group. No significant difference was seen in preoperative tumour and postoperative residual tumour volumes between the groups.
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Table 1 Results of resection between endoscopic transsphenoidal surgery using iCT (eTSSziCT) and conventional endoscope-assisted transsphenoidal surgery (cTSS) for pituitary macroadenomas
Number of cases Age, years Sex, m:f Height, mm Recurrence rate,% (n) Knosp 3–4,% (n) Initial volume, mm3 Residual volume, mm3 Resection extent,% GTR,% (n) .95% removal,% (n) .90% removal,% (n)
Total
eTSS þ iCT
cTSS
P value†
60 52.0^16.5 27:33 27.1 ^ 7.9 18.3 (11/60) 25.0 (15/60) 8805 ^ 8071 393.5 ^ 1118.5 96.9 ^ 13.5 45.0 (27/60) 60.0 (36/60) 73.3 (44/60)
30 51.5 ^ 27.0 14:16 28.4 ^ 9.0 20 (6/30) 26.7 (8/30) 10 124 ^ 8296 110.0 ^ 767.0 98.9 ^ 5.0 50.0 (15/30) 76.7 (23/30) 93.3 (28/30)
30 52.5 ^ 19.0 13:17 25.9 ^ 6.7 16.7 (5/30) 23.3 (7/30) 7964 ^ 7108 901.5 ^ 1818.0 91.7 ^ 22.2 40.0 (12/30) 43.3 (13/30) 53.3 (16/30)
0.04* 0.02* 0.001**
Note: * P,0.05, ** P,0.005. †Data are shown only in statistically significant case.
However, the resection extent was significantly higher in the eTSSziCT group than in the cTSS group (P50.04). There was no significant difference in GTR rate, but both w95% removal and w90% removal rates were significantly higher in the eTSSziCT group than in the cTSS group (P50.02 and P50.001, respectively). Additionally, we compared the results of the cTSS group (n530) with the eTSSziCT group excluding patients who did not undergo second look resection (n521). No significant difference was seen in resection extent (100+ 6.5%), GTR rate (52.4%, 11/21), and w95% removal rate (71.4%, 15/21). However, w90% removal rate (90.5%, 19/21) was significantly higher in the eTSSziCT group excluding second look resection than in the cTSS group (P50.006).
Table 2 Postoperative complications between endoscopic transsphenoidal surgery using iCT (eTSSziCT) and conventional endoscope-assisted transsphenoidal surgery (cTSS) for pituitary macroadenomas
Number of cases Transient DI Transient hyponatremia Hormone replacement* CSF leakage Postoperative haemorrage
Total
eTSS þ iCT
cTSS
60 17 (1†) 5 6 (1‡) 2 1
30 8 (1†) 2 3 (1‡) 2 0
30 9 3 3 0 1
Note: *Anterior pituitary hormones. †Permanent DI. ‡Preoperative normal pituitary function case. Other five cases had anterior pituitary dysfunction before operation.
performed on the day after first operation, and visual acuity was recovered fully.
Other results and complications A total 58 of cases (97%) were used for analysis because one case in each group was not available. The median preoperative VIS was 12 + 22.8 in the eTSSziCT group and 14+ 21.5 in the cTSS group. The median postoperative VIS was 2+ 8.5 in the eTSSziCT group and 0+ 4.5 in the cTSS group. The median improvement score (postoperative VIS – preoperative VIS) was 10+ 17.5 in the eTSSziCT group and 6+ 20 in the cTSS group. No significant differences between eTSSziCT group and cTSS group were found in preoperative VIS, postoperative VIS, and improvement score.14 The postoperative complications are summarised in Table 2. Postoperative hormone replacement therapy due to anterior pituitary hormone deficiency was needed in three patients in the eTSSziCT group and three patients in the cTSS group. Only one of these patients (eTSSziCT group) had preoperative normal pituitary function. Postoperative cerebrospinal fluid (CSF) leakage required re-operation in two patients in the eTSSziCT group. Postoperative deterioration of visual acuity due to postoperative haemorrage from the residual tumour occurred in one case in the cTSS group. The re-operation was
Discussion Intraoperative MR (iMR) imaging has recently been combined with cTSS.19–21 Intraoperative MR imaging is considered to be a useful method to detect remnant tumour in the dead angle portion of the operating microscope. However, eTSS has recently become the standard technique, replacing cTSS, so that iMR imaging is likely to be used in eTSS, resulting in improved tumour removal rate.22,23 However, MR imaging requires a special operating room, and the imaging time is quite long. Intraoperative computed tomography has advantages over iMR imaging in these areas, as special protection against magnetic fields is not needed, and the scanner is less expensive and less complex. Intraoperative computed tomography requires only about 8 minutes from discontinuation to resume the operative procedures. The latest multi-slice and high-resolution CT scanners allow clear reconstruction of both coronal and sagittal planes. Moreover, CT has particular advantages over MR imaging and other imaging methods in that evaluation of acute bleeding is intuitive and easy, and imaging of bone structures including
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bone shape and range of bone dissection is clearer and easier to interpret. However, the resolution of CT may be inferior compared with MR imaging for the detection of remnant pituitary tumour. In particular, iCT cannot differentiate normal pituitary tissue, and cavernous sinus invasion is not clear without contrast enhancement. The present study found that intraoperative evaluation of complete removal on iCT was almost consistent with w95% removal rate on postoperative MR imaging. This discrepancy between the findings of iCT and postoperative MR imaging requires attention. Future use of iCT may depend on improved imaging quality, including contrast enhancement. Magnetic resonance imaging has been the standard intraoperative imaging method for pituitary adenoma surgery. Introduction of the 0.2-T MR scanner increased the GTR rate from 43 to 70% or from 45 to 75%,24,25 or further from 58.2 to 83.6% or from 69 to 85%.26,27 High-resolution 1.5-T iMR imaging increased the removal rate from 41 to 67% or from 58 to 82%.26,27 Therefore, iMR imaging improves the GTR rate by about 25% (range 14–32%).25–29 However, no significant difference was seen between low-resolution and high-resolution iMR imaging. Intraoperative usage of CT for pituitary adenoma surgery has rarely been reported because of the relatively low resolution and very low flexibility of the imaging plane.5 Recently, iCT has been reconsidered because of the development of multi-slice, high-resolution CT with imaging slice flexibility, which allows accurate intraoperative evaluation.8 The GTR rate was 59% (first case of 89%) in a series of 33 transsphenoidal procedures using multi-slice iCT.8 In our series, w95% removal and w90% removal rates were 76.7 and 93.3%, respectively, after eTSS with iCT compared with 43.3 and 53.3%, respectively, after cTSS without iCT. However, no significant difference was observed in GTR rate between the eTSSziCT and cTSS groups. Recently, we have performed extracapsular dissection not only for microadenomas but also for macroadenomas,30 but our policy of resection was standard intracapsular removal in this study period. Therefore, tumour remnant of 5% or less was observed frequently, which mainly consisted of the tumour capsule. However, iCT without contrast medium cannot clearly detect very small tumour remnant of 5% or less, which may be one reason why no significant difference was found in GTR rate. The increase in w95% removal rate in the eTSSziCT group may be about 30% in this study, which is similar to previous improvements in GTR rate using iMR imaging.14,24,25 The increase in w90% removal rate in the eTSSziCT group may be about 40% in this study, as a result of the additive effect of endoscopy and iCT. In our series, GTR rate was low as 50.0% using
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eTSSziCT. This series included only macroadenoma cases, not including small adenoma without visual problems before surgery, but including cases with cavernous sinus invasion and recurrent tumour. The consecutive series of eTSSziCT group in this study included eight patients (26.7%) with Knosp Grade 3–4 tumours. Gross total removal could not be achieved in any of these cases using endoscopy and iCT. Gross total removal rate was 68% in only Knosp Grade 1–2 tumours. We sometimes consider gamma knife surgery for remnant tumour in the lateral side of the internal carotid artery, especially in recurrent cases. In this series, one recurrent case with Knosp Grade four adenoma was treated by gamma knife irradiation after eTSSziCT removal. Surgery for pituitary adenoma without intraoperative imaging results in improvement of visual acuity by 48–92%.20,31 Intraoperative MR imaging can directly demonstrate the optic nerve and decompression of the optic nerve.32 Pituitary surgery with iMR imaging has improved visual acuity by 66–100%.23,25,26,28 However, this improvement is similar to that obtained by the conventional procedure without intraoperative imaging.20 The present study found no cases of decreased VIS, but improvement in the VIS after eTSS with iCT was not significantly different from that after cTSS. Visual symptoms caused by pituitary adenoma may result from blood flow problems to the optic chiasm and ischaemia. Even if the optic chiasm is not perfectly free from compression, any visual symptoms will improve dramatically with improvement of blood flow.20,31,32 Therefore, any change in visual symptoms may only approximately reflect the extent of resection. iCT has inferior resolution for the optic nerve and chiasm compared to iMR imaging. However, iCT may not have disadvantages in the outcome of visual symptoms, as the present study found improvement in VIS consistent with previous reports.13 Endocrinological side effects, such as diabetes insipidus and hypopituitarism, showed no differences between the eTSSziCT and cTSS groups. However, postoperative CSF leakage occurred in two patients with giant adenoma (w4 cm) in the eTSSziCT group. The risk of CSF leakage is reported to be slightly higher (16.7%) in surgery for giant adenoma compared with normal adenomas.33 Wider exposure and more extensive arachnoid dissection may increase the risk. Expansion of the bone resection for an endoscope may also increase the risk.34 Nasal flap was not used in this series of cases. Reconstruction using nasal flap may be useful for high-flow CSF leakage after resection of giant adenoma.34,35
Limitations The present series of cTSS used for our control group was performed by microsurgery mainly with the
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endoscope. This operation technique was completely discontinued after the introduction of iCT because eTSS and iCT were introduced at the same time in our institution, so the technique of endoscopy may have been responsible for some of the observed improvements. This is a critical bias in this study, but was unavoidable since the endoscope and intraoperative diagnostic imaging were both introduced worldwide at this time.36 Our additional analysis compared the cTSS group with the eTSSziCT group excluding second look resection. No significant difference was seen in resection extent, GTR rate, and w95% removal rate. Introduction of endoscopy might be expected to have relatively stronger effect on the w90% removal rate, as was observed in this study. The improvement of results in the eTSSziCT group may be interpreted as the combined effect of endoscopy and iCT. Introduction of neuronavigation might also have improved resection results in several cases of the eTSSziCT group.37 Neuronavigation was introduced simultaneously with iCT and endoscopy in our institute. X-ray fluoroscopy was routinely used in all cases in the cTSS and eTSSziCT groups. We used neuronavigation only as a supplement for confirmation of the depth in the case of giant tumour. However, more frequent use of neuronavigation might be effective for resection of pituitary adenomas.38 Intraoperative MR imaging, especially combined with functional neuronavigation,26–28 allows more radical resections with lower morbidity. Intraoperative computed tomography-assisted endoscopic transsphenoidal surgery combined with neuronavigation might be less expensive and less complex, but achieve similar effectiveness.
Disclaimer Statements Contributors Conceiving and designing the study: MT, YY. Ethics approval: MT, YY. Collecting the data: MT, NT, FH. Interpreting the data: MT, NT, FH, KT Writing the article in whole or in part: MT, FH, YY. Revising the article: MT, YY, KT. Funding None. Conflicts of interest No conflicts of interest. Ethics approval This study was reviewed and approved by the institutional review board of Gunma University Graduate School of Medicine.
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