- Email: [email protected]
Section 4. Pituitary
Biomed Pharmacother 56 (2002) 154s–157s www.elsevier.com/locate/biopha
Mini review
Section 4. Pituitary Contemporary transsphenoidal surgery for pituitary adenomas with emphasis on complications Akira Teramoto * Department of Neurosurgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8603, Japan
Abstract The indication and complications of transsphenoidal surgery (TSS) were reported with an emphasis on our experiences. Although new therapies have been developed one after another, TSS is still main stream in the treatment of most pituitary adenomas. One century after the birth of TSS, it has evolved into a more sophisticated and less invasive procedure. The present microscopic TSS will be replaced by endoscopic TSS in the near future. Complications can occur with any surgery, but we can reduce their possibility and degree by enriching experience. In our series, the morbidity rate was 2.7%, but operative death was absent. A better understanding of the reported complications and a careful preoperative design will contribute to a better outcome of TSS. © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Transsphenoidal surgery; Pituitary adenoma; Complication
1. Recent management of pituitary adenomas
1.1. Non-functioning adenoma
Pituitary adenomas can be clinically classified into several subtypes according to their endocrinological functions; i.e.: • non-functioning adenoma; • functioning adenoma: • GH secreting adenoma (acromegaly and/or gigantism); • PRL secreting adenoma (prolactinoma); • ACTH secreting adenoma (Cushing’s disease, Nelson syndrome); • TSH secreting adenoma; • gonadotropin secreting adenoma. Each type of adenoma is treated by different strategies, which include surgery, pharmacotherapy and irradiation. In general therapeutic principles are not always uniform among neurosurgeons, endocrinologists, gynecologists and radiologists. Here our present management for pituitary adenomas will be shown especially from the viewpoints of pituitary neurosurgeons.
Since no effective pharmacotherapy is available at present, the main stream treatment for this adenoma is always surgery, which includes transsphenoidal surgery (TSS) and craniotomy. As the first step of the surgical treatment we usually select TSS in most cases, because this approach is very safe and less invasive. However, a second TSS and/or craniotomy may be necessary for huge adenomas or irregular shaped ones. Craniotomy is exceptionally indicated as the first method for a tumor in which the suprasellar volume is much larger than the intrasellar one. If we remove the intrasellar mass first by TSS, hemorrhage will occur in the suprasellar residual tumor. The residual tumor is treated with radiosurgery (gamma knife irradiation) or simply observed with MRI according to the patient’s background. The indication of the conventional irradiation is limited to very invasive adenomas.
* Corresponding author. Tel.: +81-3-3822-2131; fax: +81-3-5814-6315. E-mail address: [email protected] (A. Teramoto).
TSS is the first choice of treatment for this adenoma as the surgical success ratio is very high (60–70%). Although
© 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 0 7 5 3 - 3 3 2 2 ( 0 2 ) 0 0 2 2 6 - 3
1.2. GH secreting adenoma
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
the criteria of cure after surgery have been defined as basal GH less than 5 ng/ml, nadir GH less than 2 ng/ml in oral glucose tolerance test (oGTT) and normal IGF-1, they will be gradually revised as basal GH less than 2.5 ng/ml, nadir GH less than 1 ng/ml in oGTT and normal IGF-1. Bromocriptine (BC) is administered to the patients without endocrinological cure after surgery. It is effective for almost two thirds of acromegalic patients in whom serum GH levels decrease significantly. However, BC can hardly normalize either GH level or IGF-1 value. Daily dose is usually 7.5–15 mg. Some non-responders to BC may be treated with cabergoline, which is not now authorized by national health insurance in Japan. Octoreotide can significantly reduce serum GH in almost 90% of acromegalic patients and normalize it in approximately 50%. Since it can decrease the tumor size in 10–20% of patients, we sometimes use it for a large tumor for 2–4 weeks before surgery [6]. However, since octoreotide must be injected subcutaneously two to three times a day, it is not convenient for a long-term treatment (poor compliance). In the near future a long acting octoreotide will be placed on the market in our country. Gamma knife irradiation is followed for the patients with poor control of GH after TSS and BC treatment. 1.3. PRL secreting adenoma BC can reduce serum PRL and tumor volume in most patients with prolactinoma. However, since it cannot cure the disease, serum PRL increases again as soon as BC is withdrawn. Thus, the main fault of this medication is the absence of the goal. The second point is the presence of BC resistant cases forming 10–20% of patients with macroprolactinoma. The third one is an abrupt exacerbation of the tumor during pregnancy introduced by BC. We think that a small, enclosed tumor is a good candidate for TSS, because the normalization of serum PRL can be obtained at a high rate of almost 95%. At present MRI can provide the information not only on the tumor size but also on its invasiveness which could not be obtained in the CT era. For macroprolactinomas, we try BC treatment for a couple of months. If serum PRL level decreases to the normal or subnormal range (sensitive case), we continue BC treatment. However, we remove the tumor by TSS for other cases. The purpose of this surgery is not the normalization of PRL but mass reduction for a safer and more efficient BC treatment. The indication of irradiation for prolactinomas is limited to only some BC resistant tumors.
155s
1.4. ACTH secreting adenoma ACTH dependent Cushing’s syndrome contains two entities, such as a pituitary lesion (Cushing’s disease) and an ectopic one. It is sometimes difficult to distinguish these two disorders by routine endocrinological examinations, such as dexamethasone suppression and CRH stimulation. Although MRI can detect a tiny lesion in the pituitary gland, an incidentaloma that exists in 5–10% of the normal population may appear as a false positive finding [10]. In order to confirm the ACTH hypersecretion from the pituitary gland, we developed the selective sampling method directly from the cavernous sinus [9]. At present we will perform TSS when the results of MRI and cavernous sinus sampling are both positive. If the sampling is positive in a patient without abnormal MRI findings, we treat her/him with cortisol synthesis blockers, such as trilostane, metyrapone or op’DDD for several months. Such ‘chemical Nelson’ therapy may provide the appearance of a microadenoma on MRI. Gamma knife radiosurgery is used for the patients without remission after surgery. 1.5. Other adenomas Most TSH secreting adenomas are relatively large (macroadenomas) and often fibrous [8]. Thus, octoreotide is administered for several weeks in order to reduce the tumor mass. It can decrease serum TSH levels in most patients and tumor volume in some subjects. Although the main mass is removed by TSS, mild SITSH (syndrome of inappropriate secretion of TSH) remains in many cases. The therapeutic policy for gonadotropin secreting adenoma is essentially the same as that of non-functioning adenomas. Although some gonadotropinomas show a minimal response to BC, the main treatment is always surgery.
2. Historical aspect of transsphenoidal surgery The prototype of TSS was born in the beginning of 20th century. Jules Hardy, a Canadian neurosurgeon, completed this surgery by introducing an operative microscope and X-ray fluoroscopy in the 1960s [3]. With the marvelous progress of endocrinology, TSS had rapidly spread worldwide by the 1970s when some new words, such as prolactinoma, micro/macroadenoma, were introduced. However, at that time, the imaging evaluation of adenomas was performed by CT scan, which could not directly visualize most microadenomas. In the 1980s many papers on surgical results were published. In general, the remission ratio of functioning microadenomas ranged from 70 to 80%, while that of macroadenomas was much lower. In short, the surgical success rate chiefly depends on the size and
156s
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
invasiveness of the tumor, which can be correctly assessed by MRI. One of the advantages of TSS must be its safety and less invasiveness, because the surgical process approaches from the reverse side of the brain. We can directly observe the tumor and the normal gland, which can be preserved selectively. Since no operative scar is left on the body surface, the patient can make a comeback to normal life within a few weeks after surgery. On the contrary, the weak point of this surgery is a deep and narrow operative field from which a large and/or irregular shaped tumor can be hardly removed. In the latter half of the 1980s, the direct nasal approach was advocated as an alternative to the traditional sublabial approach. In the direct nasal approach the separation of nasal mucosa is easier and the speculum is shorter by 1 cm. However, the width of the speculum entrance is narrower (1.0–1.5 cm in diameter) compared with that of the sublabial approach (2.0–2.5 cm). Thus, deformity of the nostril or injury of the nasal ala was sometimes reported as a complication of this approach. Although there was no essential difference between these two methods at that time, the direct nasal approach was gradually replacing the sublabial approach in endoscopic TSS. In the1990s an endoscope began to be used during usual TSS in order to inspect the blind spot, such as an intracavernous tumor or suprasellar one. After a period of endoscopic assisted TSS, the pure endoscopic TSS has started [4]. However, special instruments as well as the surgeon’s technique for endoscopic surgery are not fully developed at present. In the near future the endoscopic TSS will replace the microscopic TSS in most cases. In addition to the surgical technique the intraoperative monitoring has been changing from X-ray fluoroscopy to the neuronavigator, which provides three-dimensional positional information without exposure of X-ray. If CT scan or MRI is installed in the operation room, we can easily detect the residual tumor especially if located in the suprasellar portion during surgery.
3. Complications of transsphenoidal surgery As mentioned above, the main stream treatment of pituitary adenomas must be TSS, a very safe and efficient method, although several kinds of major or minor complications have been reported and also experienced by ourselves. Complications of TSS in our 1262 consecutive TSSs for pituitary tumors are shown in Table 1. They were 445 non-functioning (35.3%), 338 GH secreting (26.8%), 227 PRL secreting (18.0%), 101 ACTH secreting (8.0%), 17 TSH secreting (1.3%) and 134 other tumors (10.6%).
Table 1 Major complications of our 1262 consecutive TSSs Number of patients CSF rhinorrhea (with meningitis) Nasal bleeding (aneurysm of ECA) Permanent DI Mucocele Carotid injury (CCF) Visual impairment Oculomotor palsy (transient) Sublabial abscess Pituitary abscess (late onset) Ventricular hemorrhage Paraventricular hemorrhage Trigeminal hypesthesia Total Mortality
6 (2) 6 (1) 5 3 3 (1) 3 2 2 1 1 1 1 34 0
% 0.48 (0.16) 0.48 (0.08) 0.40 0.24 0.24 (0.08) 0.24 0.16 0.16 0.08 0.08 0.08 0.08 2.69 0
Total morbidity ratio was 2.69%, while the mortality rate was zero in our series. These incidences are extremely low when compared with those of other reports, maybe because most patients (more than 1000) were operated on from the beginning to the end by one experienced surgeon. Another reason may exist in our therapeutic policy that the patient’s safety must surpass everything. Ciric and co-workers reported that both operative morbidity and mortality rates were significantly lower in the hands of more experienced surgeons from the results of a US national survey [1]. In their paper, the mortality rates were 1.2, 0.6 and 0.2% in a group of less than 200, 200–500 and more than 500 previous surgeries, respectively. The mean operative mortality rate for all three groups was 0.9%. From an international survey Zervas reported that the mortality rates were 0.27 and 0.86% in 2606 patients with microadenoma and 2677 patients with macroadenoma, respectively [11]. Among complications in our TSS series, CSF rhinorrhea was seen in six patients (0.48%) who needed re-operation. Mild meningitis was accompanied in two patients. CSF leaked from the tumor bed in two cases, from the gap between dura and gland in two cases, from the cribriform plate in one case and from the clivus erroneously opened in one case. In the second operation, the leaking portion was completely packed by the muscle and fascia, which were supported with a ceramic sellar plate. The sphenoid sinus was also packed with fatty tissue and sealed by fibrin glue. Postoperatively, lumber drainage was necessary for 4–5 days. CSF rhinorrhea can be prevented by the careful packing and sealing of the sella and also an adequate postoperative management including CSF drainage. Nasal bleeding was seen in six patients (0.48%) who needed re-operation. Mild to moderate epistaxis, which could be easily controlled, was not included in this series. The bleeding points were the bone edge of the sphenoidal opening in two cases, the stump of the bony septum in one case, an aneurysm of a branch of the external carotid artery
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
in one case and unknown portions in two cases. In two patients nasal bleeding occurred 3 and 6 weeks after surgery. In the latter patient, external carotid angiography detected a false aneurysm, which was embolised by the endovascular technique. Cockroft et al. reported two similar cases with delayed epistaxis (2–3 weeks after surgery) resulting from external carotid artery injury requiring embolization [2]. Permanent diabetes insipidus (DI) occurred in five patients (0.40%). Since transient DI is relatively common and easily controlled, it was not included in this series of major complications. Permanent DI occurred in two (0.4%) of 445 non-functioning adenomas, two (1.8%) of 114 Rathke’s cleft cysts and one (5.9%) of 17 TSH secreting adenomas. They have been treated with DDAVP. Mucocele of the sphenoid sinus was seen in three patients (0.24%) who needed the treatment at the ENT department. Carotid injury occurred in three patients (0.24%), one of them resulted in carotid-cavernous fistula (CCF). Internal carotid artery (ICA) was injured at the level of the sella, cavernous sinus and sphenoid sinus for each case. In two patients unilateral ICA deviated medially and in one patient with recurrent adenoma a small branch was pulled out during the curettage of the cavernous portion. Fortunately, all patients did not show any sequelae after the trapping of ICA for CCF and the meticulous packing for arterial bleeding. A false aneurysm at the C5 portion disappeared spontaneously 2 months later. Among various complications of TSS, the carotid injury is the most serious and often fatal. The incidence was reported as 1.4, 0.6 and 0.4% according to the above-mentioned stages of experience by Ciric et al. In addition to CCF and false aneurysm formation, the carotid injury may induce its occlusion or stenosis [7]. Visual impairment was seen in three patients (0.24%), all of whom had a large suprasellar tumor. Causes of visual complications may be the direct damage to the optic pathway, muscle plug compression, hemorrhage of the residual tumor or postoperative empty sella [5]. In our cases, after removal of the hemorrhagic tumor by craniotomy, two patients regained their original visual acuities, but the visual loss did not recover in one patient. Oculomotor palsy occurred in two patients with large invasive adenoma. CT scan revealed intracavernous hematoma (hemorrhagic tumor) maybe induced by the curettage of the tumor. Eye movements of both patients showed complete recovery within 8 months. Sublabial abscess in two patients and pituitary abscess in one patient were found a couple of months and 10 months after surgery, respectively. In every case the cause of
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infection was a piece of cotton sheet, which was removed to subside the disorder. A small amount of ventricular hemorrhage caused mild hydrocephalus, which was treated with ventricular drainage for a couple of days. The top of the large tumor might adhere to the floor of the third ventricle, because subarachnoid hemorrhage was absent in this case. A small hematoma was incidentally found in the caudate nucleus of the patient with Cushing’s disease. It occurred during surgery maybe due to hypertension. It was absorbed within 2 weeks with no neurological deficit. Trigeminal hypesthesia of the territory of the second branch occurred in one patient. It was due to the misdirection of the speculum that injured the infraorbital nerve. The patient complained of buccal numbness for 8 months.
References [1]
Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997;40:225–37. [2] Cockroft KM, Carew JF, Trost D, Fraser RAR. Delayed epistaxis resulting from external carotid artery injury requiring embolization: a rare complication of transsphenoidal surgery: case report. Neurosurgery 2000;47:236–9. [3] Hardy J. Transsphenoidal removal of pituitary adenomas. Union Med Can 1962;91:933–45. [4] Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 1997;87:44–51. [5] Laws Jr ER, Kern EB. Complications of transsphenoidal surgery. In: Laws Jr ER, et al., editors. Management of pituitary adenomas and related lesions with emphasis on transsphenoidal microsurgery. New York: Appleton-Century-Croft; 1982. p. 329–46. [6] Lucas-Morante T, Garcia-Uria J, Estrada J, Saucedo G, Cabello A, Alcanz J, et al. Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201–995 before transsphenoidal surgery. J Neurosurg 1994;81:10–4. [7] Raymond J, Hardy J, Czepko R, Roy D. Arterial injuries in transsphenoidal surgery for pituitary adenoma: the role of angiography and endovascular treatment. AJNR 1997;18:655–65. [8] Sanno N, Teramoto A, Osamura RY. Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma. J Neurosurg 2000; 93:194–200. [9] Teramoto A, Nemoto S, Takakura K, Sasaki Y, Machida T. Selective venous sampling directly from cavernous sinus in Cushing’s syndrome. J Clin Endocrinol Metab 1993;76:637–41. [10] Teramoto A, Hirakawa K, Sanno N, Osamura RY. Incidental pituitary lesions in 1000 unselected autopsy specimens. Radiology 1994;193:161–4. [11] Zervas NT. Surgical results for pituitary adenomas: results of an international study. In: Black P McL, editor. Secretory tumors of the pituitary gland. New York: Raven Press; 1984. p. 377–85.
Mini review
Section 4. Pituitary Contemporary transsphenoidal surgery for pituitary adenomas with emphasis on complications Akira Teramoto * Department of Neurosurgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8603, Japan
Abstract The indication and complications of transsphenoidal surgery (TSS) were reported with an emphasis on our experiences. Although new therapies have been developed one after another, TSS is still main stream in the treatment of most pituitary adenomas. One century after the birth of TSS, it has evolved into a more sophisticated and less invasive procedure. The present microscopic TSS will be replaced by endoscopic TSS in the near future. Complications can occur with any surgery, but we can reduce their possibility and degree by enriching experience. In our series, the morbidity rate was 2.7%, but operative death was absent. A better understanding of the reported complications and a careful preoperative design will contribute to a better outcome of TSS. © 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Transsphenoidal surgery; Pituitary adenoma; Complication
1. Recent management of pituitary adenomas
1.1. Non-functioning adenoma
Pituitary adenomas can be clinically classified into several subtypes according to their endocrinological functions; i.e.: • non-functioning adenoma; • functioning adenoma: • GH secreting adenoma (acromegaly and/or gigantism); • PRL secreting adenoma (prolactinoma); • ACTH secreting adenoma (Cushing’s disease, Nelson syndrome); • TSH secreting adenoma; • gonadotropin secreting adenoma. Each type of adenoma is treated by different strategies, which include surgery, pharmacotherapy and irradiation. In general therapeutic principles are not always uniform among neurosurgeons, endocrinologists, gynecologists and radiologists. Here our present management for pituitary adenomas will be shown especially from the viewpoints of pituitary neurosurgeons.
Since no effective pharmacotherapy is available at present, the main stream treatment for this adenoma is always surgery, which includes transsphenoidal surgery (TSS) and craniotomy. As the first step of the surgical treatment we usually select TSS in most cases, because this approach is very safe and less invasive. However, a second TSS and/or craniotomy may be necessary for huge adenomas or irregular shaped ones. Craniotomy is exceptionally indicated as the first method for a tumor in which the suprasellar volume is much larger than the intrasellar one. If we remove the intrasellar mass first by TSS, hemorrhage will occur in the suprasellar residual tumor. The residual tumor is treated with radiosurgery (gamma knife irradiation) or simply observed with MRI according to the patient’s background. The indication of the conventional irradiation is limited to very invasive adenomas.
* Corresponding author. Tel.: +81-3-3822-2131; fax: +81-3-5814-6315. E-mail address: [email protected] (A. Teramoto).
TSS is the first choice of treatment for this adenoma as the surgical success ratio is very high (60–70%). Although
© 2002 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. PII: S 0 7 5 3 - 3 3 2 2 ( 0 2 ) 0 0 2 2 6 - 3
1.2. GH secreting adenoma
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
the criteria of cure after surgery have been defined as basal GH less than 5 ng/ml, nadir GH less than 2 ng/ml in oral glucose tolerance test (oGTT) and normal IGF-1, they will be gradually revised as basal GH less than 2.5 ng/ml, nadir GH less than 1 ng/ml in oGTT and normal IGF-1. Bromocriptine (BC) is administered to the patients without endocrinological cure after surgery. It is effective for almost two thirds of acromegalic patients in whom serum GH levels decrease significantly. However, BC can hardly normalize either GH level or IGF-1 value. Daily dose is usually 7.5–15 mg. Some non-responders to BC may be treated with cabergoline, which is not now authorized by national health insurance in Japan. Octoreotide can significantly reduce serum GH in almost 90% of acromegalic patients and normalize it in approximately 50%. Since it can decrease the tumor size in 10–20% of patients, we sometimes use it for a large tumor for 2–4 weeks before surgery [6]. However, since octoreotide must be injected subcutaneously two to three times a day, it is not convenient for a long-term treatment (poor compliance). In the near future a long acting octoreotide will be placed on the market in our country. Gamma knife irradiation is followed for the patients with poor control of GH after TSS and BC treatment. 1.3. PRL secreting adenoma BC can reduce serum PRL and tumor volume in most patients with prolactinoma. However, since it cannot cure the disease, serum PRL increases again as soon as BC is withdrawn. Thus, the main fault of this medication is the absence of the goal. The second point is the presence of BC resistant cases forming 10–20% of patients with macroprolactinoma. The third one is an abrupt exacerbation of the tumor during pregnancy introduced by BC. We think that a small, enclosed tumor is a good candidate for TSS, because the normalization of serum PRL can be obtained at a high rate of almost 95%. At present MRI can provide the information not only on the tumor size but also on its invasiveness which could not be obtained in the CT era. For macroprolactinomas, we try BC treatment for a couple of months. If serum PRL level decreases to the normal or subnormal range (sensitive case), we continue BC treatment. However, we remove the tumor by TSS for other cases. The purpose of this surgery is not the normalization of PRL but mass reduction for a safer and more efficient BC treatment. The indication of irradiation for prolactinomas is limited to only some BC resistant tumors.
155s
1.4. ACTH secreting adenoma ACTH dependent Cushing’s syndrome contains two entities, such as a pituitary lesion (Cushing’s disease) and an ectopic one. It is sometimes difficult to distinguish these two disorders by routine endocrinological examinations, such as dexamethasone suppression and CRH stimulation. Although MRI can detect a tiny lesion in the pituitary gland, an incidentaloma that exists in 5–10% of the normal population may appear as a false positive finding [10]. In order to confirm the ACTH hypersecretion from the pituitary gland, we developed the selective sampling method directly from the cavernous sinus [9]. At present we will perform TSS when the results of MRI and cavernous sinus sampling are both positive. If the sampling is positive in a patient without abnormal MRI findings, we treat her/him with cortisol synthesis blockers, such as trilostane, metyrapone or op’DDD for several months. Such ‘chemical Nelson’ therapy may provide the appearance of a microadenoma on MRI. Gamma knife radiosurgery is used for the patients without remission after surgery. 1.5. Other adenomas Most TSH secreting adenomas are relatively large (macroadenomas) and often fibrous [8]. Thus, octoreotide is administered for several weeks in order to reduce the tumor mass. It can decrease serum TSH levels in most patients and tumor volume in some subjects. Although the main mass is removed by TSS, mild SITSH (syndrome of inappropriate secretion of TSH) remains in many cases. The therapeutic policy for gonadotropin secreting adenoma is essentially the same as that of non-functioning adenomas. Although some gonadotropinomas show a minimal response to BC, the main treatment is always surgery.
2. Historical aspect of transsphenoidal surgery The prototype of TSS was born in the beginning of 20th century. Jules Hardy, a Canadian neurosurgeon, completed this surgery by introducing an operative microscope and X-ray fluoroscopy in the 1960s [3]. With the marvelous progress of endocrinology, TSS had rapidly spread worldwide by the 1970s when some new words, such as prolactinoma, micro/macroadenoma, were introduced. However, at that time, the imaging evaluation of adenomas was performed by CT scan, which could not directly visualize most microadenomas. In the 1980s many papers on surgical results were published. In general, the remission ratio of functioning microadenomas ranged from 70 to 80%, while that of macroadenomas was much lower. In short, the surgical success rate chiefly depends on the size and
156s
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
invasiveness of the tumor, which can be correctly assessed by MRI. One of the advantages of TSS must be its safety and less invasiveness, because the surgical process approaches from the reverse side of the brain. We can directly observe the tumor and the normal gland, which can be preserved selectively. Since no operative scar is left on the body surface, the patient can make a comeback to normal life within a few weeks after surgery. On the contrary, the weak point of this surgery is a deep and narrow operative field from which a large and/or irregular shaped tumor can be hardly removed. In the latter half of the 1980s, the direct nasal approach was advocated as an alternative to the traditional sublabial approach. In the direct nasal approach the separation of nasal mucosa is easier and the speculum is shorter by 1 cm. However, the width of the speculum entrance is narrower (1.0–1.5 cm in diameter) compared with that of the sublabial approach (2.0–2.5 cm). Thus, deformity of the nostril or injury of the nasal ala was sometimes reported as a complication of this approach. Although there was no essential difference between these two methods at that time, the direct nasal approach was gradually replacing the sublabial approach in endoscopic TSS. In the1990s an endoscope began to be used during usual TSS in order to inspect the blind spot, such as an intracavernous tumor or suprasellar one. After a period of endoscopic assisted TSS, the pure endoscopic TSS has started [4]. However, special instruments as well as the surgeon’s technique for endoscopic surgery are not fully developed at present. In the near future the endoscopic TSS will replace the microscopic TSS in most cases. In addition to the surgical technique the intraoperative monitoring has been changing from X-ray fluoroscopy to the neuronavigator, which provides three-dimensional positional information without exposure of X-ray. If CT scan or MRI is installed in the operation room, we can easily detect the residual tumor especially if located in the suprasellar portion during surgery.
3. Complications of transsphenoidal surgery As mentioned above, the main stream treatment of pituitary adenomas must be TSS, a very safe and efficient method, although several kinds of major or minor complications have been reported and also experienced by ourselves. Complications of TSS in our 1262 consecutive TSSs for pituitary tumors are shown in Table 1. They were 445 non-functioning (35.3%), 338 GH secreting (26.8%), 227 PRL secreting (18.0%), 101 ACTH secreting (8.0%), 17 TSH secreting (1.3%) and 134 other tumors (10.6%).
Table 1 Major complications of our 1262 consecutive TSSs Number of patients CSF rhinorrhea (with meningitis) Nasal bleeding (aneurysm of ECA) Permanent DI Mucocele Carotid injury (CCF) Visual impairment Oculomotor palsy (transient) Sublabial abscess Pituitary abscess (late onset) Ventricular hemorrhage Paraventricular hemorrhage Trigeminal hypesthesia Total Mortality
6 (2) 6 (1) 5 3 3 (1) 3 2 2 1 1 1 1 34 0
% 0.48 (0.16) 0.48 (0.08) 0.40 0.24 0.24 (0.08) 0.24 0.16 0.16 0.08 0.08 0.08 0.08 2.69 0
Total morbidity ratio was 2.69%, while the mortality rate was zero in our series. These incidences are extremely low when compared with those of other reports, maybe because most patients (more than 1000) were operated on from the beginning to the end by one experienced surgeon. Another reason may exist in our therapeutic policy that the patient’s safety must surpass everything. Ciric and co-workers reported that both operative morbidity and mortality rates were significantly lower in the hands of more experienced surgeons from the results of a US national survey [1]. In their paper, the mortality rates were 1.2, 0.6 and 0.2% in a group of less than 200, 200–500 and more than 500 previous surgeries, respectively. The mean operative mortality rate for all three groups was 0.9%. From an international survey Zervas reported that the mortality rates were 0.27 and 0.86% in 2606 patients with microadenoma and 2677 patients with macroadenoma, respectively [11]. Among complications in our TSS series, CSF rhinorrhea was seen in six patients (0.48%) who needed re-operation. Mild meningitis was accompanied in two patients. CSF leaked from the tumor bed in two cases, from the gap between dura and gland in two cases, from the cribriform plate in one case and from the clivus erroneously opened in one case. In the second operation, the leaking portion was completely packed by the muscle and fascia, which were supported with a ceramic sellar plate. The sphenoid sinus was also packed with fatty tissue and sealed by fibrin glue. Postoperatively, lumber drainage was necessary for 4–5 days. CSF rhinorrhea can be prevented by the careful packing and sealing of the sella and also an adequate postoperative management including CSF drainage. Nasal bleeding was seen in six patients (0.48%) who needed re-operation. Mild to moderate epistaxis, which could be easily controlled, was not included in this series. The bleeding points were the bone edge of the sphenoidal opening in two cases, the stump of the bony septum in one case, an aneurysm of a branch of the external carotid artery
A. Teramoto / Biomed Pharmacother 56 (2002) 154s–157s
in one case and unknown portions in two cases. In two patients nasal bleeding occurred 3 and 6 weeks after surgery. In the latter patient, external carotid angiography detected a false aneurysm, which was embolised by the endovascular technique. Cockroft et al. reported two similar cases with delayed epistaxis (2–3 weeks after surgery) resulting from external carotid artery injury requiring embolization [2]. Permanent diabetes insipidus (DI) occurred in five patients (0.40%). Since transient DI is relatively common and easily controlled, it was not included in this series of major complications. Permanent DI occurred in two (0.4%) of 445 non-functioning adenomas, two (1.8%) of 114 Rathke’s cleft cysts and one (5.9%) of 17 TSH secreting adenomas. They have been treated with DDAVP. Mucocele of the sphenoid sinus was seen in three patients (0.24%) who needed the treatment at the ENT department. Carotid injury occurred in three patients (0.24%), one of them resulted in carotid-cavernous fistula (CCF). Internal carotid artery (ICA) was injured at the level of the sella, cavernous sinus and sphenoid sinus for each case. In two patients unilateral ICA deviated medially and in one patient with recurrent adenoma a small branch was pulled out during the curettage of the cavernous portion. Fortunately, all patients did not show any sequelae after the trapping of ICA for CCF and the meticulous packing for arterial bleeding. A false aneurysm at the C5 portion disappeared spontaneously 2 months later. Among various complications of TSS, the carotid injury is the most serious and often fatal. The incidence was reported as 1.4, 0.6 and 0.4% according to the above-mentioned stages of experience by Ciric et al. In addition to CCF and false aneurysm formation, the carotid injury may induce its occlusion or stenosis [7]. Visual impairment was seen in three patients (0.24%), all of whom had a large suprasellar tumor. Causes of visual complications may be the direct damage to the optic pathway, muscle plug compression, hemorrhage of the residual tumor or postoperative empty sella [5]. In our cases, after removal of the hemorrhagic tumor by craniotomy, two patients regained their original visual acuities, but the visual loss did not recover in one patient. Oculomotor palsy occurred in two patients with large invasive adenoma. CT scan revealed intracavernous hematoma (hemorrhagic tumor) maybe induced by the curettage of the tumor. Eye movements of both patients showed complete recovery within 8 months. Sublabial abscess in two patients and pituitary abscess in one patient were found a couple of months and 10 months after surgery, respectively. In every case the cause of
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infection was a piece of cotton sheet, which was removed to subside the disorder. A small amount of ventricular hemorrhage caused mild hydrocephalus, which was treated with ventricular drainage for a couple of days. The top of the large tumor might adhere to the floor of the third ventricle, because subarachnoid hemorrhage was absent in this case. A small hematoma was incidentally found in the caudate nucleus of the patient with Cushing’s disease. It occurred during surgery maybe due to hypertension. It was absorbed within 2 weeks with no neurological deficit. Trigeminal hypesthesia of the territory of the second branch occurred in one patient. It was due to the misdirection of the speculum that injured the infraorbital nerve. The patient complained of buccal numbness for 8 months.
References [1]
Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survey, review of the literature, and personal experience. Neurosurgery 1997;40:225–37. [2] Cockroft KM, Carew JF, Trost D, Fraser RAR. Delayed epistaxis resulting from external carotid artery injury requiring embolization: a rare complication of transsphenoidal surgery: case report. Neurosurgery 2000;47:236–9. [3] Hardy J. Transsphenoidal removal of pituitary adenomas. Union Med Can 1962;91:933–45. [4] Jho HD, Carrau RL. Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 1997;87:44–51. [5] Laws Jr ER, Kern EB. Complications of transsphenoidal surgery. In: Laws Jr ER, et al., editors. Management of pituitary adenomas and related lesions with emphasis on transsphenoidal microsurgery. New York: Appleton-Century-Croft; 1982. p. 329–46. [6] Lucas-Morante T, Garcia-Uria J, Estrada J, Saucedo G, Cabello A, Alcanz J, et al. Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201–995 before transsphenoidal surgery. J Neurosurg 1994;81:10–4. [7] Raymond J, Hardy J, Czepko R, Roy D. Arterial injuries in transsphenoidal surgery for pituitary adenoma: the role of angiography and endovascular treatment. AJNR 1997;18:655–65. [8] Sanno N, Teramoto A, Osamura RY. Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma. J Neurosurg 2000; 93:194–200. [9] Teramoto A, Nemoto S, Takakura K, Sasaki Y, Machida T. Selective venous sampling directly from cavernous sinus in Cushing’s syndrome. J Clin Endocrinol Metab 1993;76:637–41. [10] Teramoto A, Hirakawa K, Sanno N, Osamura RY. Incidental pituitary lesions in 1000 unselected autopsy specimens. Radiology 1994;193:161–4. [11] Zervas NT. Surgical results for pituitary adenomas: results of an international study. In: Black P McL, editor. Secretory tumors of the pituitary gland. New York: Raven Press; 1984. p. 377–85.