| Cavernous sinus invaded by pituitary adenomas mean the breakthrough of the inner wall of the cavernous sinus by tumors and it is very difficulty to totally remove the tumors. The treatment of giant invasive pituitary adenomas, especially, those with cavernous sinus invision are still controversial so far. There were few reports on surgical resection for those types of tumors and all of the operations were performed via craniotomy with high mortality and low rate of total removal till 1980's. The resection of those kinds of tumors via transsphenoidal approach has been increasing since 1990's, however, the low rate of intact removal and much more complication have still been remained. Nowdays, the craniotomy approach is the first choice for the resection of pituitary adenomas expanding to the anterior, middle and posterior cranial fossa, as well as for the dumb bell like and callous tumors. Combined craniotomy and transsphenoidal approach at one time are also used in the treatment of these tumors. It is very difficulty to totally remove the tumors either via craniotomy or via transsphenoidal approach.In the recent years, extended transsphenoidal approach has become the hot topic on the resection of invasive giant pituitary adenomas ,which could provide better suprasellar space visibility by removing the tuberculum sellae, bilateral bone of bottom sellae and the posterior part of planum sphenoidale, at the same time brain retraction was avoided. Today this extended transsphenoidal approach has expanded its application and could be used to deal with the tumor which invaded planum sphenoidale, cavernous sinus, dorsum sellae, the upper and middle of clivus.There are two parts such as anatomic part and clininal part in this study. In anatomic study, 9 cadaveric heads had been meidan-sagittal plane incised, and correlative structure of them had been dissected and measured with microscope. Coronal CT and MRI were scanned on 3 intact cadaveric heads, then the extended transsphenoidal operation had been mimicked with microscope, and the correlative structures had been measured. In clinical study, 54 patients with pituitary adenomas were investigated prospectively in this group. They were divided into 2 groups according to Knosp's diagnostic stardard of pituitary adenomas invading cavernous sinus. There were 22 cases classfied as grade 3 or 4 in invasive group, and there were 32 cases classfied as grade 0 to 2 in non-invasive group. The distance between cariod artery and diameter of cariod artery were measured on coronal MRI films before operation. The data and the clival rate of sellae were analyzed between groups. Extended transsphenoidal operations were perfomed on the invasive group, so did routine transsphenoinal operations on the non-invasive group.The rate of total removal of tumors and normalizing hormone level were contrasted between groups. All specimens were studied to detect the expression of Ki67, PCNA, p53, c-erB-2 using S-P immunohistochemical staining technique to analyze their relationship on oncogenesis and prognosis of pituitary adenomas invading cavernous sinus.The results are as following:1.The distances between the anterior nasal pine and sphenoidal ostium, foramen ethmoidale posterius, sphenopalatine foramen, anterior opening of pterygoid canal,the entrance of Dorello canal were 59.61±4.67 mm,67.88±4.43 mm,53.12±2.20 mm,57.94±3.31 mm,61.00±2.73 mm. The angles between the sagittal plane and the plane decided by above lines and their projections on basis cavum nasi plane (the angles mentioned below are the same) were 33.1±3.7°,36.3±7.43°,19.1±3.6°,12.9±3.3°,28.1±3.6°.2.Optic tubercle that appeared merely in sphenoid sinuses was 27.3%, appeared merely in ethmoid sinuses was 31.8%,appeared in both sides was 40.9%, the frepuency of optic nerve-carotid artery recess was 68.2%. The distance between anterior nasal spine and the recess was 76.16±5.32mm, the angle was 33.8±4.2°.3.The distance between ophthalmic artery initiation point and anterior nasal spine was 72.88±6.78 mm, the angle was 30.3±3.7°. The distance between foramen lacerum and anterior nasal spine was 79.38±5.32 mm, the angle was 32.7±3.9°, the frequency of carotid artery eminence in sphenoid sinus was 68.2%. To resect ventral bone of cavernous sinus along the optic-carotid artery recess, and remove the posterior part of optic canal and part of petrous apex by extended transsphenoidal approach could thoroughly liberate the internal carotid artery. 4.The distance between the entrances of Dorello canal was 19.76±1.98 mm, the each vertical dimension to petrosal process was 18.07±2.83 mm, the vertical dimension of the corresponded spot of pharyngeal tubercle to petrosal process was 25.66±4.68 mm, the distance between the anterior nasal spine and the furcation of basal artery was 95.70±7.53 mm.5.The distance between the tuberculum sellae and the posterior edge of the cribriform blate was 22.72±3.64 mm, between the medial edges of both olfactory tract 15.12±1.84 mm. The distance between the anterior nasal spine and the foramen rotundum 76.94±3.76 mm, and the angle was 20.7±3.2°.6.The operation of extended transsphenoidal approach could appropriately remove the posterior ethmoid sinus, tuberculum sellae and sphenoid bone platform and manifest basal part of frontal lobe, anterior cistern of optic chiasma,A1 & A2 segment of ACA,AcoA; The incision of the anerior and medial wall of CS could disclose the CS segment of ICA and its branches; To remove the dorsum sellae and the posterior wall of the sphnoidal sinus, and incise the dural of the upper and medial clivus, could disclose the structures such as pon,BA and its branches,,SCA,PCA etc.7.The positive stainings of Ki67, PCNA and p53 are distributed in nuclear of tumor cells, otherwise, the positive stainings of c-erB-2 were in the cytoplasm of tumor cells.8.The expression of Ki67, PCNA in pituitary adenomas invading cavernous sinus (68%,64%)was much higher than in non-invasive pituitary adenomas(34%,28%)(p<0.01).9.The expression of c-erB-2 in pituitary adenomas invading cavernous sinus (59%)was higher than in non-invasive pituitary adenomas (28%)(p<0.05). there no significant difference of the expression of p53 between invasive group and non-invasive group(27%,22%)(p>0.05).10. The distances between two sides inner cariod artery with pituitary adenomas were significant wider than these of in normals on MRI films 6.98±3.45 mm(p<0.01). there were no significant difference between grade 3 group 23.12±4.33mm and non-invasive group23.08±4.61 (p>0.05),but tthey were much wider in grade 4 group(31.28±4.23) contrasting to others (p<0.01).The diameters of cariod artery in grade 4 group were significant smaller than in other groups (p<0.05). 11.The more than 30°of ultimate angle of the clival sellae on coronal MRI film were found in 7 cases (3 microadenoma) among 19 patients in invasive group, 3 cases were unable to observe because of tumor breakage.In non-invasive group only 3 cases had clival sellae (ultimate angle <10°).The rate of clival sellae cases in 2 groups was significant difference (p<0.05).The clival sellae may be related to the invasiveness of tumor to cavernous sinus.12.Tumor was totally removed in 13 patients, subtotally in 7 patients in invasive group and removed totally in 26 patients, subtotally in 6 patients in non-invasive group.The total removal rate of tumor between 2 groups(59%,81%) had not statistical difference (p>0.05)13.The corresponding hormones for functional pituitary adenomas became normal in 9 cases (PRL 6/9, GH 2/4,ACTH 1/1) and decreased more than 50% level that those of pre- operation in 5 cases in invasive group, normal in 13 cases (PRL 8/11,GH 3/5, ACTH 2/3) and decreased more than 50% in 11 cases in non-invasive group.The hormone normalizing rate of PRL and GH pituitary adenomas between 2 groups had not statistical difference (p>0.05).Several conclusions are drawn according the study,and lists as following:1. Extended toward the anterior sellar, through the ETSA, lesions located among the region with the posterior edge being the anterior limit, the medial wall of the optical canal and lamina papyracea being the lateral limit, could be managed. The bottom of the frontal lobe, optical chiasm, and the complex of AcoA could be observed when the decompression of optic cana througgh this way was feasible.2. Extended toward the parasellar, the structures in the CS could be seen and the lesions here could be managed through ETSA. This approach used in treating lesions such as cavernous aneurysms and paraclinoid aneurysms is credible.3. Extended toward the posterior sellar, the lesions located in the area of upper and middle clivus the entrance of the dorello canal being the lateral limit could be managed through ETSA. The pons, BA and its branches, PCA and SCA, etc, could be seen when the subarachnoid space was opened. The ETSA used in treating aneurysms of the upper BA should be credible.4. Extended transsphenoidal approach is a feasible and effective method for the removal of pituitary adenomas invading cavernous sinus, especially for the resection of tumors with bilateral invasion of cavernous sinus. The tumor within cavernous sinus were well exposed via extended resection the bone of bilateral sellae more than the distances between cariod artery. The advantages of this approach are minmal injury and less postoperative complications.5. Ki67, PCNA, c-erB-2 might become the index of invasiveness and prognosis of pituitary adenomas. The clinical detaction for Ki67, PCNA, c-erB-2 may reflect the pituitary adenomas that have potencial invasiveness. In addition, the clival development of sphenoidal sellae may have relation to cavernous sinus invasiveness of pituitary adenomas...
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