Abstract

Background: The endoscopic endonasal transsphenoidal approach has become standard for the management of pituitary adenomas. This approach has been shown to facilitate early recovery and discharge from the hospital. The early recovery protocol has many advantages for both patients and the healthcare system in terms of patient satisfaction and cost-effectiveness.

Methods: Forty-seven patients with pituitary adenomas who underwent a trans-nasal endoscopic approach at our institution, operated by one neurosurgeon and one ENT surgeon, were retrospectively studied. Enhanced recovery protocols entailed preoperative, intraoperative, and postoperative protocols. The standard care included 1 day postoperative intensive care unit admission plus 1 or 2 days in the ward. Patient satisfaction was measured in terms of resolution of chief complaint, and a questionnaire survey was conducted at discharge and the 3-month follow-up.

Results: There was a significant decrease in the length of hospital stay with a mean of 2.7 days (standard deviation = 0.74). Patient satisfaction was better at the 3-month follow-up than in the early postoperative period. Most of our patients improved in terms of biochemical cure (18 out of 25 functioning adenomas [72%]) and experienced resolution of the chief complaint. The death occurred in only one patient due to pulmonary embolism.

Conclusion: Our study supports the benefits of early recovery protocols for endoscopic endonasal surgery for pituitary adenoma resection. The procedure is both safe and efficacious and improves overall patient satisfaction. Cerebrospinal fluid leaks remain a challenge but may improve with the use of fat, fascia lata, or middle turbinate flaps for large defects.

Keywords: Early recovery after surgery, Endonasal, Endoscopic, Outcome, Pituitary adenoma

INTRODUCTION

Early recovery protocols for spine surgeries have been well-established in recent reports.[ 16 ] Such protocols were initially introduced for colorectal and urological surgeries aiming to augment patient recovery and minimize the length of hospital stay (LOS). This, in turn, had an impact on both the patient and the healthcare system. Early recovery after surgery (ERAS) frameworks have the potential to increase efficiency and cost savings for neurosurgical practices. However, clear recommendations for such frameworks are lacking for patients with pituitary disease.[ 1 ]

Pituitary adenomas are common, mostly benign primary intracranial tumors and represent about 15% of all intracranial tumors. More than one half of these neoplasms are functioning and associated with over-secretion of one or more hormones, while the other half are non-functioning.[ 6 , 8 ]

All pituitary adenomas are surgical lesions, with the exception of some prolactinomas. The surgical indications include the presence of one or more mass effects such as visual impairment, hormonal dysfunction, and the most critical, pituitary apoplexy. With recent increases in pituitary research, the treatment algorithm is tailored according to the adenoma subtype. This encompasses surgical resection, preand/or post-operative medical therapy, and postoperative radiation therapy in selected cases.[ 15 , 19 ] The most accepted standard surgical approach is the transsphenoidal procedure, which is suitable for most midline adenomas. The transcranial approaches, namely, subfrontal or pterional, are still well-suited for adenomas with parasellar extension.[ 4 ]

In the past few decades, the pure endoscopic endonasal transsphenoidal approach has become the gold standard for most pituitary adenomas. A few reports have shown that the pure endonasal approach has more efficacy and safety compared to that found with the trans-septal or transsphenoidal.[ 5 ] Recent literature has shown that both approaches have similar outcomes in terms of morbidity and mortality.[ 11 ]

The application of ERAS is not new in neurosurgical practice. It has been proposed in minimally invasive spine surgeries compared to traditional open approaches to limit opioid use and to be more cost effective. Very few reports have shown that ERAS has been used in skull base surgeries without clear guidelines.[ 10 ]

We want to present our experience of treating pituitary adenomas, underling the role of the pure endoscopic endonasal approach to achieve control of these tumors. Safety and efficacy are reported here in terms of neurological, hormonal, and visual outcomes. The main goal of treatment is to improve patient satisfaction and reduce morbidity rates.

MATERIALS AND METHODS

For the past 2 years, 47 patients (25 females and 22 males) with histologically confirmed pituitary tumors or adenomas who underwent the trans-nasal endoscopic approach were retrospectively studied in our facility. All cases were operated by the same team of one neurosurgeon and one ENT surgeon. Indications for surgery were tumors producing a mass effect, hormonal disturbance with failure of medically treatable adenomas, or progressive neurological and visual disorders requiring surgical intervention. All patients underwent endoscopic endonasal surgeries by a team of expert pituitary neurosurgeons and a dedicated ENT surgeon. All patient data were collected, and surgical complications were analyzed.

Preoperative assessments included neuroradiological, endocrinological, and visual evaluations and routine preoperative blood tests. A magnetic resonance imaging (MRI) of the pituitary with gadolinium contrast was done for the sellar region to delineate the adenoma and para- and/or suprasellar extensions, if any.

The adenomas were classified according to MRI appearance. According to the Hardy–Wilson classification, they were grouped into micro- and macro-adenomas with diameters less or more than 10 mm, respectively.[ 20 ] Cavernous sinus invasion was evaluated according to the Knosp classification method using MRIs before surgery.[ 12 ]

Before surgery, the protocol of ERAS starts with patient and relative education that includes a description of the surgical technique and all available alternatives. This was followed by an explanation of all possible complications and informed consent for ERAS. Older age and comorbidities were considered as challenges for this protocol. For this group, an intense preoperative evaluation and strict control of any medical condition was mandatory. The benefits of ERAS were discussed and contact phone numbers for both the hospital and doctor were delivered to enhance the communication. The expected postoperative course was explained, along with how possible complications would be managed.

Before surgery, fasting is advised for 8 h, and in some cases, regular medications such as antihypertensives are permitted. Dexamethasone 8 mg intravenous injection is administered at the time of induction along with antibiotics such as 2 g intravenous ceftriaxone. Other anesthetic medications are given to help prevent early awakening and to reduce postoperative nausea and vomiting; remifentanil and propofol are preferred.

All patients receive arterial and urinary catheters to facilitate intra-operative hypotension, and to calculate the urine output in the intra- and postoperative period. The cutoff for diabetes insipidus is a urine output of more than 250 mL/h. At that point, the Minirin^© 60 µg tab is started 3 times daily.

The same surgical team performed all procedures. Surgical consent has been taken from each patient including risks, benefits, and possible complications. The usual surgical steps include first placing the patient in the supine position with the head centered on a head rest. After orotracheal intubation, the oropharynx is packed with a piece of gauze to prevent any blood or fluid leak into the airway or stomach. The trunk is elevated 10° and the head is kept in a neutral position, sometimes turned 10° toward the operating surgeon. The eyes of the patient are protected with antibiotic cream. The nasal phase is performed through a single nostril up to the anterior sphenoidotomy after identification of the sphenoid ostium. A rescue nasal flap is prepared for those with large tumors. The posterior part of the septum is removed to gain enough space for both the endoscope and one instrument inserted through one nostril, whereas the main instrument is inserted through the other nostril. The procedure is a two surgeon, two nostril approach. In some selected patients (cases with severe septal deviation), the trans-nasal transseptal technique is used to access the sphenoid sinus.

After removing the sphenoid face, the sellar floor can then be identified in the center with planum and clivus anterior and posterior, respectively. Removal of the intrasphenoidal septa is done with caution to prevent injuring the internal carotid artery (ICA) or optic nerve. Lateral to the sellar floor, the prominences of the ICA and optic nerves can be seen with the optico-carotid recess in-between.

We use a bone chisel and a Kerisson bone rongeur to open the sellar floor. This is followed by incision of the dura using a scalpel in a cruciate manner. Tumor removal starts with an average volume biopsy, which proceeds with a dissection and suction of the remaining part. This dissection starts at the lateral edges, followed by the inferior portion. The superior or anterior portion should be the last part to be removed to guard against the descent of the diaphragm. A careful dissection, appropriate hemostasis, and normal pituitary gland preservations are the keys to avoiding a prolonged postoperative period.

At the end of the procedure, the anesthesiologist starts cessation of the hypotensive technique to the basal blood pressure at the time of induction. Once hemostasis is rechecked, a meticulous reconstruction of the sellar floor defect is performed. If no obvious leak is observed, Gealfoam^© and Sergicell^© agents are usually utilized. When a cerebrospinal fluid (CSF) leak is observed, the defect is sealed with fat and fascia lata. In very large defects, a nasoseptal or middle turbinate flap is added to the reconstruction. This is very important to avoid any extra days spent during the LOS. We do not use any lumbar drains to accelerate discharge.

On recovery from anesthesia, ondansetron 8 mg is used in conjunction with pantoprazole 40 mg intravenously to prevent postoperative nausea and vomiting. A 2 g paracetamol intravenous infusion is administered to minimize opioid use [ Table 1 ].

Table 1:

The frequency of length of LOS in patients who underwent the ERAS protocol.

Early mobilization is encouraged to facilitate recovery. In selected cases, acetazolamide 250 mg tab is given on postoperative day 1 after 2 h of recovery when oral fluids are started. The dose is adjusted according to the intraoperative findings of possible CSF leak. The dose can be one tablet daily up to 4 times. The addition of topiramate 25 mg tablets twice daily can be added in those who develop profound CSF leaks. A salty sensation in the throat is treated as postnasal CSF leakage as well.

After postoperative day 1 in the ICU, the 2^nd postoperative day in the ward is the most important for deciding on discharge status from the hospital. If a patient has a smooth recovery without signs of early diabetes insipidus, electrolyte imbalance, or CSF leaks, the patient is usually prepared for discharge. If any other complications occur, 1 or 2 days more are recommended in the hospital.

We manage diabetes insipidus very early using desmopressin tablets, depending on urine output as an early indicator. The daily electrolyte level disturbances are very early and promptly managed. An early weaning of hydrocortisone is started before discharge. We order full pituitary hormone levels on the 2^nd postoperative day. In case of any hormonal disturbances, we refer the patient to endocrinology care.

For our patients, we rarely performed postoperative computed tomography (CT) scans. We advise brain CT scans only in cases of postoperative neurological deficits or disturbed consciousness levels. The patient was instructed on discharge to obtain an MRI sella with contrast 3 months from surgery time.

At the time of discharge, usually on postoperative day 2, in the absence of any complications, instructions are given to the patient and their relatives to contact us over the phone or come back to the hospital in case of any warning signs of complications. Education is provided regarding events such as persistent CSF leaks (not intermittent) diabetes insipidus by observing the color and timing of urination, and any visual or neurological symptoms. We also discuss the benefits of using social media like WhatsApp^® for rapid communications. Patient satisfaction was measured in terms of resolution of the chief complaint and the questionnaire survey at discharge and 3 months of follow-up.

At the 3-month follow-up following MRI with contrast, gross total tumor removal was confirmed when no contrast-enhanced remnants could be detected. Subtotal or partial removal was confirmed if any remnants were observed.

RESULTS

Overall, 53.2 % of our patients were female. The mean age was 55.3 [ Figure 1 ]. Of 47 patients, 42 (89.4%) were macroadenomas (Rang = 20:44 mm), while 5 (10.6%) were microadenomas. Cavernous sinus invasion was evaluated according to Knosp classification as follows: G0 = 20 (42.5%), G1 = 13 (27.7%), G2 = 9 (19.1%), G3 = 3 (6.4%), and G4 = 2 (4.3%). Fourteen patients (29.8%) had endocrinological symptoms as the first presentation, and the next was headache experienced by 13 patients (27.7%). Visual impairment and other neurological symptoms in the form of oculomotor nerve palsy were seen in 10 (21.3%) and 1 (2.1%) patients.

Figure 1:

Chart description of gender in relation to age in our study.

Non-functioning adenomas were seen in 22 cases (46.8%). Of the functional adenomas, hormonal hyper-secretions were as follows: prolactin (PRL) 12 (25.5%), growth hormone (GH) 7 (14.9%), mixed GH and PRL 5 (10.6%), and ACTH 1 (2.1 %) [ Figure 2 ].

Figure 2:

Illustration of functional adenomas with secreting hormone percentages. PRL: Prolactin hormone, ACTH: Adrenocorticotropic hormone, GH: Growth hormone, NF: Non-Functioning adenoma

There was a significant decrease in the LOS with a mean of 2.7 days (standard deviation = 0.74). Patient satisfaction was better in the 3-month follow-up versus early postoperative period. Overall, 30 (63.8%) patients considered their early discharge as satisfactory, and 9 (19.2%) were moderately satisfied. Eight (17%) were not satisfied and believed that a longer LOS would have been preferred if it was possible.

Most of our patients improved in terms of a biochemical cure (18 out of 25 functioning adenomas (72%)) and relief of the main presenting symptom. The most devastating complication was death, which occurred in only one patient on the 3^rd postoperative day due to a pulmonary embolism. The most common surgical complication was a CSF leak in six cases (12.8%). It occurred transiently for the 1^st day after surgery in five cases and responded well to the medical management. In one patient (2.13%), it was persistent despite of best medical treatment for 6 days.

Visual acuity was normal in 25 (53.2%) and abnormal in 22 (46.8%). Postoperative visual improvement was documented in 17 (36.2%) patients. Improvements observed immediately in the postoperative period were seen in 9 (52.9%) patients, while the remaining 8 (47.1%) had improved vision at the 3 month follow-up. In five patients, the vision was the same as the preoperative status. No visual deterioration was observed postoperatively.

Readmission and reoperation for an overlay large fat graft was done in only one patient, and early epistaxis occurred in only one patient. The bleeding stopped with anterior nasal packing without readmission to the OR. Immediate postoperative third nerve palsy developed in one patient (2.1%). The patient who developed a CSF leak was readmitted after 6 days of surgery after failure of medical treatment for a CSF leak.

Gross total tumor removal at 3 months of MRI was observed in 34 patients (72.3%). The rest of our patients (27.7%) had remnants in difficult regions like the cavernous sinus [ Figures 3 and 4 ].

Figure 3:

Magnetic resonance imaging sella with contrast at the 3-month follow-up showing (a and b) Coronal and sagittal views of preoperative images with a tumor within the sella with homogenous enhancement characteristic of a pituitary adenoma. (c and d) Coronal and sagittal views of postoperative images show tumor removal within the Sella, but contrast enhancing pseudo-capsule is still present in spite of growth hormonal level control in this patient.

Figure 4:

Magnetic resonance imaging sella with contrast at the 3-month follow-up showing (a and b) Coronal and sagittal views of preoperative images with the tumor extending to the suprasellar region reaching the floor of the third ventricle. (c and d) Coronal and sagittal views of postoperative images showing gross total tumor.

DISCUSSION

For the past three decades, the endoscopic endonasal approach has been widely used for treating pituitary adenomas. However, the transcranial subfrontal or pterional approaches are still sometimes required, especially for giant lesions. In rare cases, a simultaneous endoscopic endonasal and transcranial combined approach is a surgical option for giant difficult adenomas.[ 13 ]

There are two different techniques to access the sphenoid phase during the endoscopic endonasal approach. With the pure trans-nasal technique, the endoscope and instruments are inserted through the space between the nasal turbinates and septum. This allows for a binostril approach where one instrument can be inserted with the endoscope through one nostril and others from the contralateral nostril. In the trans-septal approach, a corridor is created through the nasal septum after dissection and elevation of the nasal mucosa. It is ultimately a one nostril approach. Instruments, along with the endoscope, are passed through a nasal speculum.[ 7 , 9 ] In this work, we used non absorbable nasal packing for all the cases (32 trans-nasal and 15 trans-septal), which was removed 48 h after surgery.

The average LOS in the recent literature for endoscopic techniques was reported to be 3–4 days. For the microscopic trans-nasal transsphenoidal approach, the length of LOS was approximately 5–8 days.[ 3 , 14 , 17 ]

In this study, we present our experience with endoscopic endonasal surgeries with an ERAS protocol. The mean LOS was 2.7 days, with the longest stay 5 days and the shortest, 2 days. For 21 patients, the LOS was only 2 days [ Table 1 ].

We believe that an experienced skull base team is mandatory to achieve this protocol. The endoscopic endonasal learning curve requires time and practice to reduce the complication rates to a level that permits an accelerated discharge. With the high rate of pituitary cases and team work with neurosurgeons, ENT surgeons, and endocrinologists, the postoperative complications are dramatically reduced, and the mortality as well.[ 14 ]

In our series, patient satisfaction was evaluated based mainly on the resolution of the chief complaint. Most of our patients improved in terms of a biochemical cure (18 out of 25 functioning adenomas [72%]), and pain relief was experienced in nine out of 13 patients with headaches (69.2%). Postoperative visual improvement was documented in 9 out of 10 (90%); however, visual deterioration did not occur postoperatively. In a series of 57 patients operated on at a center of excellence, the median LOS was 3 days. In their study, the biochemical and hormonal improvement was (90%), and that for vision was (92%).[ 17 ] Their outcomes were somewhat similar to our results except for the headache outcomes. This can be explained as headaches usually persist in the postoperative period, and sometimes, there are other causes, such as tension headaches or referred from the cervical spine. In one report, rates of headache improvement after the endoscopic endonasal approach were not related to tumor volume or its extension to surroundings. In such reports, headaches were unlikely to improve in younger patients, microadenomas, and low mental health scores.[ 18 , 21 ]

In our study, readmission and reoperation for an overlay large fat graft was done in only one case. We had one mortality on postoperative day 2 documented to be from a pulmonary embolism, which was probably related to preoperative comorbidities. Therefore, we believe that the enhanced recovery protocol should be considered, and all patients should be thoroughly evaluated preoperatively.[ 2 ] In case of a well-established comorbidity such as severe hypertension, uncontrolled diabetes mellitus, and morbid obesity, this protocol should not be applied.

The limitations of our study were the small number of patients and the lack of a cost-benefit analysis. The small number was attributed to the collaborative team of one neurosurgeon/one ENT surgeon. Nevertheless, there was a decrease in the burden on the hospital and the health care workers. Being a public university hospital, the patients did not pay anything.

Lidocaine infusion can be used as part of a multimodal analgesia approach, as illustrated in the table 2 . Narcotic free (non-opioid) pain relief methods such as nonsteroidal anti-inflammatory drugs or acetaminophen can be used intra- and postoperatively. Both approaches can be part of multimodal pain management with no direct comparison in our study. Although the current standard practice in the centers of excellence for pituitary tumor surgeries has such protocol of enhanced recovery in our university hospital, we have our preliminary results of such a protocol.

Table 2:

Summary of our preliminary enhanced recovery protocol.

CONCLUSION

Our study results suggest that the early recovery protocol for endoscopic endonasal surgery for resection of pituitary adenomas can be considered as a standard approach. Experienced skull base pituitary surgeons are mandatory for the application of such a protocol. This will ensure that the LOS becomes dramatically shorter and patient satisfaction improves. Reduction of healthcare costs is of paramount importance, especially in developing countries.

Ethical approval:

The Institutional Review Board has approved the ethical approval for this study, Institute name:Faculty of Medicine , Zagazig University, Zagazig, Sharkia, Egypt. And approval date is 2 October 2023. Approval number: IRB#: 11143- 2/10-2023.

Declaration of patient consent:

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship:

Nil.

Conflicts of interest:

There are no conflicts of interest.

Use of artificial intelligence (AI)-assisted technology for manuscript preparation:

The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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