Microsurgical Resection of Pituitary Adenoma via Single-Nostril Transsphenoidal Approach ======================================================================================== * Hengzhu Zhang * Xian Zhang * Hongmei Du * Yongkang Wu * Lun Dun * Lei She * Xiaodong Wang * Xueqiang Shi * Cunlin Xu ## Abstract **OBJECTIVE** To explore the methods and experience of the single-nostril transsphenoidal approach for treating pituitary adenomas. **METHODS** We retrospectively analyzed 46 patients who had pituitary tumors and received surgery via the single-nostril transsphenoidal approach and observed the effects and complications of surgery. The specific surgical methods are: a nasal speculum is inserted slowly through the right nostril towards the anterior wall of the sphenoid sinus. A 1.5 cm incision is made into the nasal mucosa in the right nasal cavity at the level of the middle nasal turbinate. By fracturing the bony septum, a space is formed between the bilateral nasal mucosa and the bony septum of the sphenoid sinus. Then, the inside of the sphenoid sinus is exposed. The remaining part of the bony septum, the anterior sphenoid sinus wall, and the sphenoid mucosa are gradually removed. The anterior sphenoidotomy is less than 1.5 cm wide. Aft er confirming the tumor by dural puncture, a cross incision of the dura is made, and the tumor is slowly removed by curett e. The sella is usually collapsed and visible after the total tumor removal. When the tumor is resected satisfactorily, gelatin sponges are placed into the operative cavity to stop bleeding. **RESULTS** Postoperative MRI scans revealed that among the 46 cases, total resection of the tumor was achieved in 34 cases and subtotal in 12. No deaths or disability occurred, and the hormone levels of almost all patients improved. Signs of diabetes insipidus occurred in 17, electrolyte disturbances in 5, and there were no reports of postoperative cerebrospinal fluid rhinorrhea. **CONCLUSION** The direct single nostril transsphenoidal approach of continuous improvement has the advantages of a convenient approach, simplified operation, safety and high efficiency. KEY WORDS: * single-nostril * transsphenoid approach * microsurgery * pituitary adenoma ## Introduction At present, resection of the pituitary adenoma via single-nostril transsphenoidal approach is commonly used in the treatment of pituitary adenoma. With the accumulation of clinical experience, the techniques of the transsphenoidal approach have been greatly improved, especially the single-nostril transsphenoidal approach, in which the anterior wall of the sphenoid sinus can be exposed directly to the sella. Furthermore, the surgical path and the procedure are simple, and there is less damage to the nasal mucosa; therefore, it has been widely utilized in patients with pituitary adenoma in clinical practice. In our hospital, since the introduction of the single-nostril transsphenoidal approach in July 2006, 46 cases of pituitary adenoma have achieved a satisfactory therapeutic outcome from use of the procedure. This paper presents the reports of these cases as follows. ## Patients and Methods ### Patients A total of 46 patients with pituitary adenoma were included in this study, in which 18 were male and 28 female, with the mean age of 35 ranging from 25 to 79 years old. The course of the disease ranged from 3 months to 6 years. Several clinical signs and symptoms were observed in the patients, including amenorrhea in 21 cases, lactation in 16, detrimental loss in sexual function in 6, infertility in 18 cases, hyperthyroidism in 6, acromegalia in 2, headache in 39, vision decline in 11 (3 of them with monocular, the other 8 cases with binocular), visual field defects in 6, and elevated blood glucose in 6. Abnormal levels of endocrine markers, such as triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), PRL, GH, free cortisol, and androgens were detected in these patients. As a result, each patient was diagnosed with an adenoma; therefore, preparations for surgery were made. ### Radiological assessment Preoperative radiological evaluation included computed tomography (CT) or magnetic resonance imaging (MRI). In the study patients, the sphenoid sinuses were pneumatized, and the size of the sphenoid sinuses were normal in 13 cases, extended in 26, and extended with bone destruction in 7. The tumor diameter ranged from 1.1 mm to 3.2 mm in the patients, and it was > 20 mm in 23 cases and > 30 mm in 2 (Fig. 1). ![Fig. 1.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/6/6/446/F1.medium.gif) [Fig. 1.](http://www.cancerbiomed.org/content/6/6/446/F1) Fig. 1. Preoperative MRI films: a cashew-shaped 1.6 cm × 1.8 cm × 1.4 cm lesion, located in the sellar region; the optic nerves were mildly compressed, and the sphenoid sinus was well pneumatized. The inferior portion of the arc-shaped sella tursica ruptured into the sphenoid sinus; the bilateral internal carotid arteries were not involved. ### The procedure of the operation Ephedrine (0.25%) was instilled in the nasal cavities bilaterally 3-4 times per day for 3 days before the operation, and prednisone was administered to the patients for 3 days, with 5 mg each time, t.i.d. The patients’ nasal mucosa was shaved and cleaned the day before the operation, and routine preparation for general anesthesia was also performed. The patients were placed to maintain a horizontal position, with a head hypsokinesis of 15°, and the eyes and eyebrows were protected with antibacterial plastics. The bilateral nasal cavities were repeatedly disinfected with chlorhexidine alcohol, and 1% ephedrine was given in aerosol to contract vessels of the mucous membrane in the nasal cavity, thereby preventing and decreasing local bleeding. An incision in the mucosa was made in the right nasal cavity at the level of the middle nasal turbinate. By fracturing the bony septum, a space was formed between the bilateral nasal mucosa and the bony septum of the sphenoid sinus. The remainder of the bony septum, the anterior wall of the sphenoid sinus, and lining mucosa in the sphenoid were removed gradually. The incision of the anterior sphenoidotomy should be made at 1.0-1.5 cm wide. The inside of the sphenoid sinus was then exposed. After the sphenoid sinus mucosa was stripped and electrocoagulated, the convex sellar floor was revealed. The sellar floor was chiseled and expanded with a 1.2-1.5 cm bone window until the dura mater was exposed. Upon confirmation of the tumor after dural puncture, the tumor was resected by curette through a cross incision of dural mater. When the tumor was completely removed, the sellar septum was collapsed in most cases. The nasal cavity hollowed by removing the adenoma was packed with adipose or gelfoam. Fibrin glue (Tisseel, Immuno, Vienna, Austria) was used to keep the mucosa in place. The nasal septum and the nasal mucosa were reset after removal of the tumor. Upon completion of surgery, vaseline gauze or an expansive sponge was packed in the involved nostril and was then removed 36-48 h after surgery. One study patient, a 47-year-old male had a history of a neck mass for 10 years. The mass had appeared benign but grew gradually until the patient became symptomatic suffering from palpitations and weight loss. The patient had been treated for hyperthyroidism, in which methimazole had been prescribed for 10 years, but the symptoms had not been alleviated. MRI imaging demonstrated the typical features of a sellar tumor, and the diameter was approximately 2.7 cm. Then the patient was diagnosed with a pituitary adenoma and admitted to our hospital. On physical examination the patient was conscious and emaciated, and his vision and mentality were normal. His response to stimuli was nimble, and both pupillae were round, equal in size, and sensitive to light. The thyroid was enlarged with a 9.7 cm × 3.9 cm × 4.5 cm right lobe, a 9.0 cm × 4.2 cm × 3.9 cm left lobe, and it was firm and without tenderness. The patient’s heart rate was elevated, 120 beats per minute; there was no abnormalities in limb movement. Laboratory studies showed the following: T3 at 6.27 nmol/L, T4 at 260.10 nmol/L, FT3 at 17.22 pmol/L, FT4 at 76.06 pmol/L, TSH at 9.93 Mu/L. In addition, the level of each factor was higher than the respective standard value. Based on the above clinical data, the patient was diagnosed with a TSH-secreting pituitary tumor and central hyperthyroidism. ### Preparations for surgery The patient was transferred to the endocrinology department of our institution and given octreotide for 1 week. The symptoms of palpitations disappeared, and the patient’s thyroid gland decreased in size and became soft. A subsequent MRI showed that the pituitary adenoma had become smaller. Laboratory studies showed that FT3 at 7.23 pmol/L, FT4 21.4 at pmol/L, and TSH at 0.65 Mu/L. Therefore, preoperative preparations were made to be ready for surgery. The patient received resection of tumor via single-nostril transsphenoidal approach on July 14, 2008. The operation was successful, and the pituitary adenoma was resected subtotally using a microscope. The patient was again transferred to the endocrinology department for secondary hyperglycemia and for high levels of FT3 at 29.82pmol/L, FT4 at 68.72 pmol/L, TSH at 6.00 Mu/L. He was discharged on July 30, 2006, with the endocrine studies of FT3 27.65 pmol/L, FT4 104.13 pmol/L, TSH 1.32 Mu/L. After discharge, the patient received the radiation therapy 2 times. ### Postoperative management All patients in our group were asked to lie on their back for 5-7 days after surgery. Routine clinical data was monitored and recorded for 2 days. The patients were informed that blowing their nose or sneezing should be avoided, so as to avoid cerebrospinal fluid leakage after possible shifting of the sellar floor mucosa. The patients received contrast MRI scans of the sellar region 1-3 days after surgery to assess the outcome of the tumor resection. All such patients should have index endocrine levels checked postoperatively, and if the hormone levels are below normal, replacement therapy should be initiated. Antibiotics were administered for 7-9 days after surgery, and blood biochemical indexes studies were repeated regularly, with special attention paid to serum electrolytes which were monitored so as to maintain a balance between water and electrolytes. ## Results All patients were discharged uneventfully, and the patients could eat the following day after the surgery; the average time of hospitalization was 12 days. In the 46 cases, 34 had a complete resection of the tumor, and 12 had subtotal removal of the tumor. These findings were confirmed by MRI imaging (Fig. 2). Complications such as cerebrospinal fluid rhinorrhea, optic nerve injury, perforation of nasal septum did not occur in the 43 cases of which the inferior portion of the sella was not repaired. Transient diabetes insipidus occurred in 17 cases with the urine volume around 4,000-5,000 ml a day; therefore, pituitrin and minirin were administered for 4-10 days to control urine volume. All of the patients suffering from transient diabetes insipidus recovered soon after with effective management. Hypokalemia and hyponatremia presented in 5 patients. Following surgery, vision was improved in all of the patients in comparison to their vision before surgery. In the 32 patients with GH-secreting pituitary adenomas, 11 demonstrated decreased levels of hormone to less than 40% of that before surgery, while the remaining 21 cases returned to normal levels. Furthermore, the 3 cases with low levels of hypophyseal hormones demonstrated somewhat increased levels postoperatively, and they were treated with long-term hormone replacement therapy. In 1 case with a TSH-secreting pituitary adenoma, the tumor was firm, therefore, the resection was subtotal, and the hormone level of the patient was not improved postoperatively; however, the patient’s condition was improved following radiotherapy and hormonotherapy. ![Fig. 2.](http://www.cancerbiomed.org/https://www.cancerbiomed.org/content/cbm/6/6/446/F2.medium.gif) [Fig. 2.](http://www.cancerbiomed.org/content/6/6/446/F2) Fig. 2. Postoperative MRI films: the sellar region tumor was entirely resected; the pituitary morphology returned to normal and optic nerve compression was not found. ## Discussion ### Development of transsphenoidal surgical approach The transsphenoidal surgical approach has been used for more than a century. Schloffer first originated a left lateral rhinotomy approach in 1907[1], and Hirsch developed the inferior nasal approach in 1909[2]. Cushing combined the ideas of Hirsch’s submucosal separation and Helstead’s incision under the lip to form the nostril transsphenoidal approach[2]. Surgical techniques were improved due to the availability of the intraoperative microscope in the 1950s, and this approach became the standard for resection for lesions in the sella. The technology was introduced to China in 1981, and during the past 23 years, it has been utilized for the resection of sellar tumors[3]. The outcome of surgery has shown that Hardy’s approach is a mature surgical technique; however, after surgery, upper lip swelling and numbness, nasal septum perforation, and other complications may develop[4]. For these reasons, therefore, the nasal-nasal septum-transsphenoidal approach was initiated in China and has been proven to be more convenient, with little bleeding, and without the complications of Hardy’s approach[5]. ### Advantages of the treatment for pituitary adenomas via the single-nostril transsphenoidal approach The purposes of treatment for pituitary adenoma include resection or reduction of the pituitary gland, regaining visual function, improving the status of hormone hypersecretion, and protecting and restoring normal pituitary function. The methods of treatment for pituitary adenoma include drug therapy and surgery. Some PRL adenomas may be controlled by drugs such as bromocriptine, but for the most of cases, surgical treatment is required. Presently, the single-nostril transsphenoidal approach can be carried out in 90% of pituitary adenoma patients. The advantages of the approach are as follows. The route to the pituitary adenoma can be more direct with a shorter distance to the sella, in comparison to the transcranial approach, and neoplastic and pituitary tissue can be distinguished more clearly. Further, the tumor can be resected more thoroughly. Intraoperative surgical risks, such as injury of the visual pathway and of other structures are less. The patients’ response is less severe, and recovery is quicker. It has been proven that the single-nostril transsphenoidal approach is more effective in optic nerve decompression and in eyesight protection[6]. In comparison with the sublabio-septo-sphenoidal approach, the nasal vestibule-septo-sphenoidal approach, and ethmoidsphenoidal approach, the single-nostril transsphenoidal approach has several advantages[7]: it minimizes the trauma of the oral and nasal mucosa which bleeds easily, and the approach can avoid the possibility of injury of the nasopalatine and upper alveolar nerves. Further, there is no surgical incision made in the approach, so it has a good cosmetic outcome, less trauma, and shorter intraoperative duration. ### Experience from the single-nostril transsphenoidal approach The nasal mucosal incision should be made as closely to the anterior sphenoid sinus as possible. Firstly, the incision is made about 1.0 cm long, and then the mucosa is stripped off using a nerve dissector under careful observation. When it is confirmed that the boat-form incision in the anterior wall of the sphenoid sinus is located right in the middle of the anterior sphenoidal wall, appropriate adjustments of the mucosal incision up to 1.5 cm long is made in order to expose the sellar floor. Special treatment of the sellar floor is unnecessary in most of the cases, unless there is a need during surgery to use adipose tissue for blocking the cerebrospinal fluid leakage. Only the gelatin sponge is used for filling in the intra-sellar space. Previously, a vaseline gauze packed into the nasal cavity was applied for hemostasis, and at present, an expansion sponge coated with chlortetracycline ointment filled in the nasal cavity is employed, with a better effect of hemostasis in most cases. As the approach includes an inherent long and narrow path to the sellar region and as it is difficult to expose the lateral area, it can be difficult to stop bleeding effectively with ordinary straight bipolar electrocoagulation tweezers when the lateral nasal mucosal is bleeding. We found that bipolar electrocoagulation tweezers with a curved cutting edge, long, straight, and bayonet-shaped are convenient for the surgeon to get to the bleeding site without blocking vision. Theoretically, sellar reconstruction could have several beneficial effects. First, it could reduce the occurrence of a postoperative CSF leak by creating a physical barrier through healing and fibrosis. Secondly, it could prevent intracranial infection. Intracranial infection is usually associated with a CFS leak, but in the absence of cerebrospinal fluid leakage it may also occur[8]. If an intracranial infection is identified while performing a tumor resection, we routinely perform sellar reconstruction. The decision to perform sellar reconstruction or not depends on the presence of an intracranial CSF leak, and not on tumor size (more than 2 cm). That is, even though the tumor is very small, reconstruction is needed if CSF occurs during the operation. The materials used for reconstruction of the sella are fat, muscle, or fascia following the tumor resection. It has been reported in foreign literature that if hydroxyapatite made with chassis is applied, it can play a supportive role, and its effect can be very advantageous[9,10]. ### Supplementary treatment Supplementary treatment includes drug therapy and radiation therapy. There are different views on the treatment against PRL adenomas. Since the invention of dopamine receptor agonists, it has become the first choice in drug therapy in the treatment of PRL adenomas, and it is administered orally[11]. The mechanism of action of dopamine receptor agonists is to depress PRL levels and to reduce the size of tumor[12]. In addition, it should be mentioned that the drug therapy can only relieve the symptoms by inhibiting the secretion of PRL; however, the tumor cells cannot be completely terminated. When the drug is no longer used, the tumor cells tend to grow rapidly, and PRL levels increase again. Therefore, surgical removal of tumor may eventually be necessary[13]. In our study group, drug therapy, such as bromocriptine, mesilate or radiotherapy was given to patients with prolactin-secreting adenomas when there was residual tumor or when PRL level remained high. MRI has demonstrated that radiotherapy is not needed in cases of which total resection was performed because some reports have shown that radiation can cause irreversible damage to the pituitary. Ten years after radiotherapy, approximately 90% of patients experienced hypopituitarism[14]. TSH-secreting pituitary tumors are clinically rare and only account for 1%-2.8% of pituitary tumors[15]. This type of adenoma has the clinical features of moderate progression, latent growth, and most patients with this tumor are diagnosed as having Grave’s disease. It almost always presents as a pituitary macroadenoma, and its mean diameter is 2.3 cm[16]. The treatment for TSH-secreting pituitary tumors is much different from that for Grave’s disease. If the treatments typically used for primary hyperthyroidism were used for TSH-secreting pituitary tumors, then, as a result, not only would there be failure to adequately control central hyperthyroidism, but the growth of a pituitary tumor could be prompted. Clinical symptoms of TSH-secreting pituitary tumors include goiter, skin, hot flashes, and weight loss. The diagnosis of this disease is always delayed, and most cases are treated the same way as Grave’s disease is treated. The FT3 and FT4 levels in TSH-secreting pituitary tumor patients are increased, and TSH remains elevated or normal. After treatment of Grave’s disease, TSH levels are increased in most cases. Imaging studies have demonstrated that there are no differences between TSH-secreting pituitary tumor and other types of pituitary tumors. Surgery is the first choice of treatment for TSH-secreting pituitary tumors. Octreotide or lanreotide is administered before surgery to alter thyroid hormone levels. In general, the transsphenoidal approach is utilized in treating this type of pituitary tumor, and the transtemporal approach can be used for macroadenomas. The difficulty in this operation is that in some cases, the tumor cannot readily be thoroughly removed because the high expression of bFGF (basic fibroblast growth factor) carcinoma cells cause the tumor to become fibrotic and hard. As the tumor cells infiltrate into the peripheral tissue, including into the cavernous sinus, the internal carotid artery, and the optic chiasm, it can be difficult to completely resect, and as a result, the tumor may recur. * Received October 12, 2009. * Accepted December 8, 2009. * Copyright © 2009 by Tianjin Medical University Cancer Institute & Hospital and Springer ## References 1. Jörgen L. A Century of Pituitary Surgery: Schloffer’s Legacy. Neurosurgery 2007; 61: 865-868. [PubMed](http://www.cancerbiomed.org/lookup/external-ref?access_num=17986949&link_type=MED&atom=%2Fcbm%2F6%2F6%2F446.atom) 2. 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