Short-Term Complications of Microscopic Trans Nasal Transsphenoidal Pituitary Adenomectomy

Background/Objective : The commonest of pituitary gland tumors is pituitary adenoma which may be excised transcranially or trans nasal trans sphenoidal using either microscope or endoscope, in this study, the microscope was used. The objective was to see the short-term outcome of patients after microscopic transnasal trans-sphenoidal pituitary adenomectomy. Material & Methods : This was a descriptive prospective study carried out from July 2019 to July 2021. 80 cases were included. All patients were investigated by contrast brain MRI, hormonal assay for pituitary gland & visual perimetry . Patients were evaluated for complications at 48 hours and 7 days. Results : Mean age of the study population was 41.78 ± 11.75 years. There were 61 (76%) men & 19 (24%) women. 55 (68.8%) patients had functioning and 25 (3.3%) patients had nonfunctioning adenoma. Among 33 (41.3%) patients size of the adenoma was < 0.9 cm and 47 (58.8%) patients had adenoma > 1.0 cm. 12 patients had CSF leaks within 48 hours of surgery and 5 had a persistent leak on the 7 th day. No statistically significant association was seen between age, gender, and size of adenoma and persistent CSF leak (P > 0.05). Diabetes insipidus was found in 9 patients. 3 had post-operative hematoma, 01 patient had meningitis and 2 patients died. Conclusion: microscopic transnasal trans-sphenoidal surgery is a safe procedure yet associated with significant complications.


INTRODUCTION
The pituitary gland is termed the "master gland" of the human body as, despite its tiny size, it influences practically every major organ. 1 The anterior lobe of the pituitary gland, also termed adenohypophysis, is made up of five separate types of cells that release six different types of hormones. Lactotrophs generate prolactin (PRL), somatotrophs create growth hormone (GH), corticotrophic cells release adrenocorticotropic hormone (ACTH), thyrotrophs produce thyroidstimulating hormone (TSH) & gonadotrophs secrete follicle-stimulating hormone (FSH) & luteinizing hormone (LH). The hypothalamus is known to influence the synthesis of these hormones. Hormonal production is also influenced by negative feedback regulation from the target organ's hormone products.
The neurohypophysis secretes two hormones: antidiuretic hormone (ADH) and oxytocin. A pituitary adenoma is the most common pituitary gland tumor. 1 Some pituitary tumors produce too many hormones, which otherwise govern critical bodily systems. On the contrary, certain pituitary tumors may impair normal pituitary gland activities, resulting in reduced hormone production. [2][3] The prevalence of pituitary tumors or adenomas is frequently reported based on autopsy or MRI data. 4 An epidemiological research found that pituitary adenomas can affect up to 16.5 percent of people. 5With an estimated frequency of 16.7 percent, the bulk of them are larger than 10 mm in size (14.4 percent in autopsies & 22.5 percent in radiological findings). [5][6] Pituitary adenomas are characterized according to their size, secretion, and histology. Tumors with a diameter of 9 mm are called microadenomas, whereas those with a diameter of more than 9 mm are called macroadenomas. Giant adenomas are tumors that are ≥ 4 cm. The hormones secreted by functioning adenomas are categorized, for example, growth hormonesecreting and prolactinomas. A pituitary tumor can be formed by any of the pituitary gland's many cell types. Nonfunctioning tumors do not create clinically significant increases in hormone levels. However, even among nonfunctioning tumors, a variety of tumor forms are observed, including null cell and oncocytoma. 7 Management of pituitary tumors is defined by their types and size. 5 Operative treatment is usually considered for debulking the tumor mass to achieve the betterment of visual disturbance and other presenting complaints 8 . It is observed that diagnoses and excision have increased remarkably over the past 2 decades and transsphenoidal resection has been on increasing trends while transcranial resections have notably decreased. 9 Transnasal trans-sphenoidal pituitary surgery is a frequent operative treatment that is now recognized as the standard surgical approach to sellar lesions due to the benefits of enhanced visibility and low invasiveness. This has been described as a safe and successful way of removing pituitary tumors. This is a common treatment these days, although there are some possible problems, such as cerebrospinal fluid (CSF) leak, infections, electrolyte imbalance, vascular, endocrinologic, and rhinological abnormalities. 4,10 The purpose of this study was to look at patients' short-term outcomes following microscopic transnasal transsphenoidal pituitary adenomectomy. Complications prolong hospital stay, putting additional strain on limited resources, and complications such as meningitis can be deadly.

Study Design & Setting
A descriptive prospective study (Quasi observational study) was carried out at Services Hospital Lahore & Surgimed Hospital from July 2019 to July 2021. This study included 80 cases and a nonprobability consecutive sampling technique was used.

Inclusion Criteria
Patients diagnosed with pituitary adenoma on MRI brain plain & contrast, both genders, between the age group of 18 -60 years were part of this study.

Exclusion Criteria
Those patients younger than 20 years or older than 60 years, with recurrent tumors & tumors other than adenomas, were excluded from the study. We also excluded those who did not agree to be part of the study.

Data Collection
Eighty patients with pituitary tumors were studied. All patients fulfilling the criteria were admitted through our patient department of Services Hospital Lahore or Surgimed hospital Lahore. Informed consent was obtained either from the patients or attendants. The patient's name, age, sex, and address were obtained initially along with detailed history. All patients were investigated by an MRI brain plain & contrast, pituitary hormonal assay (cortisol, prolactin, growth hormone, Insulin-like growth factor-l, follicle-stimulating hormone, luteinizing hormone, thyroid function tests) visual perimetry & baseline investigations to ensure the patient is optimized for surgery. Follow-up of the patients was done at 48 hours and 7 days to record shortterm post-operative complications of trans nasal transsphenoidal pituitary adenomectomy. SPSS 23 was used to enter and analyze all of the data.

Surgical Technique
After informed consent & induction of general anesthesia, nasal preparation and positioning of the patient (placed supine with neck 10 -15 degree extended and nasal tip in line with right anterior superior iliac supine) nasal speculum was placed in the right nostril. Middle turbinate was identified, about 1cm distal to it, the root of the septum until an anterior wall of sphenoid sinus was identified. With the help of the speculum, the septum was subluxed and deviated. Then microscope was brought into the field and the sphenoid sinus was opened by an osteotome. Then the floor of the sella was opened, dura revealed which was diathermized and a midline incision was made with No. 11 blade. The tumor was debulked intracapsularly.
The tumor was resected piecemeal by use of ring curettes, pituitary rongeurs, suction, and irrigation. After tumor removal floor of the sella was reconstructed with fat from the right lateral thigh, surgicel and bone chips saved during submucosal resection.
Sphenoid sinus was packed with fat, the speculum was removed, septum returned to midline and mucosa was placed back and both the nostrils were packed with BIPP (Bismuth iodine paraffin paste) soaked gauze and a sterile dressing was done for48 hours. The patient was nursed in a supine position with a head-end elevation of 30 degrees. The patient was evaluated for complications at 48 hours & 7 to record in the Proforma.

Age Distribution
The average age of the patients was 41.7811.75 years. The patient's minimum and maximum ages were 20 and 60 years, respectively.

Relation of Persistent CSF Leak with Age, Sex, and Size of Adenoma
CSF leak present on the 7 th day was labeled as the persistent CSF leak & its relation with the age, sex & size of the tumor was determined (Tables 4-6).

DISCUSSION
Trans-sphenoidal pituitary surgery is a frequent operation that has become the primary treatment for sellar lesions. 11 Although trans-sphenoidal surgery has been consistently described as a safe & successful treatment for pituitary tumor removal, it is not risk and complication-free 12,13 .
Persistent cerebrospinal fluid (CSF) rhinorrhea post-operatively is one of the most pertinent causes of morbidity following trans-sphenoidal surgery for pituitary adenomas 14 .
With regards to surgical complications of transsphenoidal surgery, CSF leak remains to be the most common and disturbing postoperative morbidity. It is described that the success of intraoperative reconstruction of sella following dissection is a major determinant of postoperative CSF leak. Postoperative CSF leak is a common complication of transnasal transsphenoidal pituitary adenomectomy & encountered in reported series of 0.5 -15%. 15,16 A local study, describing the complications of transsphenoidal surgery, cited the prevalence of postoperative CSF leak as 3.9%. 17 The major risk factor for the post-operative CSF leak is the intraoperative leak, non-meticulous repair of the sella is another important factor. 16,18 In this study, it was observed that 12 (15%) of the patients had CSF leak which was managed conservatively however persistent CSF leak was only in 5 (6.25%), after microscopic transnasal transsphenoidal pituitary adenomectomy. Patients' age, gender, and size of the tumor were stratified to see the impact of these variables on CSF leak after transnasal transsphenoidal pituitary adenomectomy. But results showed no significant association between CSF leaks.
Henry Jung from the USA reported postoperative CSF rhinorrhea was 1.7%. 19 However this rate of 1.7% is very low as compared to the frequency of CSF in this study which is 6.25%.
Gao et al. published a meta-analysis of the results & consequences of endoscopic and microscopic transsphenoidal surgery for pituitary adenomas. According to his results, the postoperative CSF leak was rather severe (12.8 percent vs. 12.2 percent for the endoscopic and microscopic groups, respectively). 20 A study reported that CSF leakage was observed in ten patients (40%) who were treated with a transsphenoidal microscopic approach 10 . Adam A Razak in his study presented his early experience and compared endoscopic surgery with microscopic experience. As per his findings, CSF leak rates were the same in both study groups. Six patients (15%) in the MTSS (microscopic transnasal trans sphenoidal) group and four (10%) in the ETSS (endoscopic transnasal transsphenoidal) group had postoperative CSF leakage (p-value = 0.74). 21 In this study, CSF leak was comparable to our study for microscopic transnasal transsphenoidal pituitary adenomectomy.
Diabetes insipidus was observed to be the second most common complication after CSF rhinorrhea i.e. 11.25% (9 patients). However, it was transient in most cases (8 patients). A study by Chowdhury and others showed post-operative DI at 14.8% slightly higher than our study however it was transient in this study aswell 22 .
Randeva et al. observed a 16% incidence of transitory diabetes insipidus in pituitary apoplexy patients throughout their hospital stay. DI following trans-sphenoidal surgery was considered to be caused by compression or damage of the neurohypophysis and interrupted blood supply of the gland or an edematous pituitary stalk. Pituitary apoplexy is usually restricted to the adenohypophysis; however, it can occur in the posterior lobe as well. 23 Pesky et al. found that 9.0 percent of individuals had transitory DI and 1.4 percent had persistent DI. They also discovered a much greater rate of transient DI in functional adenomas than in nonfunctional adenomas (16.6 percent vs. 3.4 percent). 22,24 Post-operative hematoma at the operative site following any intracranial surgery is the most cumbersome complication usually arising within the first 24 hours, resulting in serious morbidity or even mortality, if not coped timely. 22 In a study, 15 patients (10%) patients 22 developed this complication however, in our study it was very low i.e., 3.75%.

CONCLUSION
Trans nasal trans-sphenoidal microscopic surgery is considered a safe procedure but like any other surgery, it also carries the notable risk of postoperative complications. In our study, CSF leak was found most coon complication followed by diabetes insipidus. In this study, no relation of CSF rhinorrhea could be established to age, gender, or size of the tumor. A more meticulous approach and use of new gadgets & materials (like the use of fibrin glue while reconstructing sella) may help in further decreasing the complication rate.

Limitations
Surgeons with different expertise and experience performed the surgery. No long-term complications were included in this study.