Key-words:
Cotton swab - endoscopic - extracapsular dissection - pituitary adenoma - transsphenoidal
surgery
Introduction
Endoscopic transsphenoidal surgery (ETSS) for pituitary adenoma (PA) is one of the
most commonly performed procedures in neurosurgery. With gross total PA resection
set as the preferred goal, extracapsular dissection is encouraged to identify a tissue
plane or cleavage between tumor's pseudocapsule and normal pituitary gland, arachnoid,
or diaphragma sellae. Gentle separation of this plane ought to yield complete PA removal
while lowering complication rates. Prevedello et al. reported, in 2013, the extracapsular
dissection technique using a cotton swab.[[1]] Although it appeared intriguing, clinical outcome by this particular technique
does not exist. The primary objective was, first, to evaluate the effectiveness and
safety of this technique. The secondary aim was to analyze factors associated with
the extent of tumor resection by ETSS.
Materials and Methods
Patient population
The prospectively maintained data of consecutive patients undergoing ETSS for PA from
January 2014 to December 2017, performed by the senior author (AH), was reviewed.
Only cases with pathology-confirmed PA were included. Each patient's preoperative
demographics and clinical presentation were classified based on visual disturbance,
endocrinological condition, and prior treatment for PA or asymptomatic presentation.
Surgical technique
All patients underwent ETSS, through binostril access, with the operating surgeons
standing on their right side. Surgical technique, for the nasal, sphenoidal, and sellar
phases, was similar to the previously narrated steps in our earlier publication.[[2]] Switching from curettage for PA removal, the senior author (AH) utilized cotton
swab since 2014, as described by Prevedello et al.,[[1]] for extracapsular dissection [[Figure 1]]. The intraoperative data, including suspected or definite residual PA, and complication(s)
were recorded. For cerebrospinal fluid (CSF) leakage, grading was based on Esposito
et al.[[3]] The method for sellar defect repair, depending on CSF leak grade, was similar to
our previous literature.[[2]] Although the cotton swab technique was undertaken in all of the cases, patients
who had internal debulking only without circumferential pseudocapsule resection, as
their intended surgical goal, were excluded from our analysis.
Figure 1: Endoscopic image shows utilizing a cotton swab for extracapsular dissection. The
plane between overlying arachnoid and the pseudocapsule (capsule) of the tumor (solid
curve line) was established along with the plane separating tumor and the normal pituitary
gland (dotted line)
Pre- and post-operative assessment
For patients with visual disturbance, their visual acuity (VA) and visual field (VF)
were assessed using Snellen chart and automated Humphrey perimetry, respectively.
The visual function would be examined again, using the same methods, after ETSS at
6-month interval. When compared to preoperative data, the VA and VF outcomes were
classified into improved, stable, or worse.
Regarding endocrinological status, preoperative pituitary hormone panel was obtained
in every patient. Each hormone was classified as hyperproduction (in functioning PAs),
normal, or deficiency. After ETSS, the hormone profiles were examined during the hospital
stay and again, at 3-month interval. Functioning PA was considered in remission when
the current standard criteria were met after surgery.[[4]],[[5]],[[6]] Any new postoperative hormonal deficit, with or without postoperative hormone replacement
therapy, was documented.
Preoperative radiographic, computerized tomography and/or magnetic resonance imaging
(MRI) scan, features were grouped based on sphenoid pneumatization [[7]] and modified Hardy's classification.[[8]] For parasellar extension of the tumor, modified Knosp grading was applied to coronal
view evaluation.[[9]] Enclosed (Knosp 0, 1, 2) versus invasive adenoma (Knosp 3, 4) were categorized.
From MRI scan at 12-month after ETSS, complete resection versus residual tumor was
determined. For PA volume, each patient's pre- and post-operative MRI scans were calculated
by drawing of the region of interest with OsirixLite software (Pixmeo Sarl, Bernex,
Switzerland). The percentage of tumor resection was obtained by the pre- minus postoperative
volume and divided by preoperative volume.
Postoperative in-hospital complications, such as apoplexy or CSF leakage requiring
surgical repair, were noted. After hospital discharge, included patients must have
had at least 1 year of follow-up with postoperative MRI scan, endocrinological, and
visual assessment. Numerical data would be presented as mean (standard deviation)
or median (interquartile range) where appropriate. Utilizing STATA statistical software
version 14.2 (StataCorp, College Station, Texas, USA), logistic regression analysis
was applied to identify positive and negative predictors, for the extent of resection
and CSF leakage, of ETSS. P < 0.05 was considered statistically significant.
Results
Of the 222 consecutive cases during the study period, forty patients with non-PA were
excluded from our assessment. Another 72 patients had only internal debulking for
decompression. Their surgeries were without the initial aim to completely remove the
tumor due to the giant size of PA. Hence, those cases were not included. Ten other
patients with inadequate data and/or follow-up were omitted, leaving 100 cases for
our examination. The median follow-up time was 18.26 months (12.76, 35.16).
Patient demographics, clinical presentation, and preoperative radiographic features
[[Table 1]]
Table 1: Patient demographics, clinical presentation and preoperative radiographic features
(m=100)
The mean age of patients was 50.41 years old (13.96) with equal proportion of both
genders. Among the 50 patients with visual disturbance, forty of them (80%) had abnormal
VA, whereas 46 (92%) had VF defect. Eighty-one patients (81%) had nonfunctioning PA.
Nineteen functioning PAs (19%) were eight growth hormone-producing, five adrenocorticotropic
hormone-producing, four prolactinomas, and two mixed hormone-producing adenomas. There
were eight patients (8%) who presented with pituitary apoplexy. The median duration
of symptom, in these symptomatic patients, was 12 months (3.24). Nineteen cases (19%)
were recurrent Pas, whereas 14 patients (14%) had residual tumors without notable
enlargement. Of the 34 patients who underwent pituitary surgery before our ETSS, they
had an average of one prior procedure (range 1–5 procedures). Three patients had radiation
therapy after multiple surgeries. Roughly two-thirds of the cohort had at least one,
or more, the axis of the preoperative hormonal deficit.
Most of the PAs were macroadenomas (97%) with the median preoperative volume of 5.35
ml (2.7, 10.15). The majority of tumors were sizeable, having 73% Hardy stage C and
85% invasive adenoma. There was no difference in right-sided (44%) versus left-sided
(43%) position of the normal pituitary gland. Sellar-type sphenoid pneumatization
was found in 73%.
Intraoperative findings and short-term complications [[Table 2]]
Table 2: Intraoperative data and complications (n=100)
During ETSS, definite residual PAs were observed in 56 patients. Six cases had suspected
tumor remaining. There was no internal carotid artery injury, but the majority (78%)
had intraoperative CSF leakage, with Grade 1 being the most common. For short-term
complications, postoperative CSF leakage, requiring repeat endoscopic endonasal repair,
occurred in one patient with Grade 2 and two patients with Grade 3 intraoperative
leakage. Three patients developed meningitis (3%). One of the three ensued from postoperative
CSF leakage, whereas the other two patients did not have postoperative leakage.
Logistic regression analysis of risk factors associated with intraoperative CSF leakage,
shown in [[Table 3]], demonstrates that modified Hardy stage A was the only protective factor against
intraoperative CSF leakage (P = 0.013). Although the increasing age of patients seemed
to be influential from univariate analysis (P = 0.028), this factor almost reached
statistical significance by multivariate assessment (P = 0.058). Other nonsignificant
factors were gender, pre- or postoperative tumor volume, sphenoid pneumatization,
modified Knosp grade, intraoperative residual tumor, and complete tumor removal.
Table 3: Factors for intraoperative cerebrospinal fluid leakage
As for postoperative CSF leakage requiring ETSS for repair and meningitis, grade 1
intraoperative CSF leakage was the only protective factor against these complications
(P = 0.040) [[Table 4]]. Age, gender, pre- or postoperative tumor volume, sphenoid pneumatization, modified
Hardy stage, Knosp grade, intraoperative residual tumor, and complete tumor removal
were nonsignificant elements.
Table 4: Factors for postoperative cerebrospinal fluid leakage and meningitis
Postoperative long-term outcomes
Extent of resection
Comparing preoperative to 12-month postoperative MRI scans, 43 cases had total tumor
removal, whereas 57 cases had residual PAs. For all ETSS, the median postoperative
volume was 0.2 ml (0, 1.33). The mean percentage of tumor's volume removal was 83.87%
(23.52).
From the logistic regression analysis, Knosp 4 (P = 0.007) and history of previous
surgery (P < 0.001) were the strong negative factors, in multivariate evaluation,
for achieving total tumor removal [[Table 5]]. Although preoperative tumor volume (P = 0.022) and nonfunctioning PA (P = 0.017)
were negative factors in univariate evaluation, they did not reach a significant level
by multivariate assessment. Other factors, such as age, gender, modified Hardy stage,
or intraoperative CSF leakage, were insignificant.
Table 5: Factors associated with total tumor removal
Visual outcomes
From the 50 patients who presented with visual symptoms, after ETSS, VA improved in
72%, whereas 26% remained stable. VF defect improved in 69% and was unchanged in 29%.
One patient, who had prior multiple surgeries and radiotherapy, suffered worsening
of her VA and VF after ETSS. All six patients with preoperative ophthalmoplegia improved
after surgery.
Hormonal outcomes
At the last follow-up (minimum of 1 year) post-ETSS, remission of functioning PAs
was achieved in 13 of 19 patients (68.42%). The majority of patients (67%) had unchanged
postoperative hormonal status while 11% incurred, one or more axis, new deficit.
Discussion
ETSS for PA is becoming the standard of care.[[10]],[[11]],[[12]],[[13]] When possible, extracapsular dissection should be implemented for effectiveness
and safety. Prevedello et al. proposed the utilization of a cotton swab for this particular
maneuver.[[1]] Abandoning the ring curettes for tumor resection that the senior author (AH) had
employed since 2006,[[2]] the Prevedello's technique was adopted, for extracapsular dissection, from 2014
until present. Despite many years of the very publication, clinical data to support
its value still does not exist. We believe this study is the first to report clinical
and radiographic outcomes of the cotton swab technique.
Our results confirmed that cotton swab for extracapsular dissection of PA was effective
as shown by the remission rate for functioning PA at 68.4%, comparable to previous
reports.[[14]],[[15]],[[16]],[[17]],[[18]],[[19]] Regarding its safety, there was no life-threatening complication. One patient (2%)
with prior extensive treatments did suffer worsening of her vision. Postoperative
CSF leakage and meningitis were 3%. These rates were in line with previously reported
series for postoperative CSF leakage at 1.4%–16.9%[[13]],[[20]],[[21]],[[22]],[[23]],[[24]] and meningitis at 0%–10%.[[3]],[[13]],[[23]]
Rather disappointing was the rate of complete tumor removal at 43%, below the reported
range from literature at 62.4% to 90%.[[13]],[[20]],[[25]],[[26]],[[27]],[[28]],[[29]],[[30]],[[31]],[[32]] Yet, given our intraoperative observation of 62, combined definite and suspected,
residual PAs, this was not unexpected. From the logistic regression analysis in [[Table 5]], Knosp 4 proved to be the negative factor for total PA removal. This concurred
with our intraoperative finding that most of the remaining tumors were in the cavernous
sinus. In addition, previous surgery was also an unfavorable factor for achieving
total tumor removal, similarly to reports by others.[[13]],[[33]] This outcome might, indeed, reflect the fact that our cases were made up of large
or postsurgical PAs as tertiary care center would have received from other hospitals.
Another likely explanation, for the below-average total PA resection rate, could be
that the senior author (AH) frequently exercised caution, by less aggressive tumor
resection, for fear of higher grade CSF leakage. Thin pseudocapsules, with marked
arachnoid adherence, were not removed in many older, unlike younger, patients for
this very reason. The result from the logistic regression analysis in [[Table 3]] reiterated this bias from the surgeon. In addition, having mostly nonfunctioning
PAs could have an impact for the less vigorous resection than those with functioning
PAs. It could have potentially caused our lower rate of total tumor removal. This
influence was also evident by univariate analysis in [[Table 5]].
Our study limitations are as followed. Despite prospectively collected data, the retrospective
analysis yielded lower power of evidence. The second pitfall could be the high percentage
of difficult PAs, i.e., previous surgery or invasive adenomas. They had a significant
impact on the outcomes regardless of surgical technique. Moreover, the selection bias
by the operating surgeon could have affected the total PA resection as aforementioned.
In spite of some imperfect results, extracapsular dissection technique using a cotton
swab proved its safety and effectiveness.
Conclusion
The outcomes of ETSS by cotton swab technique for extracapsular dissection demonstrated
its effectiveness and safety. It should be increasingly utilized by more surgeons
for widespread practice. Again, confirmed by our study, previous surgery and Knosp
4 were negative factors for achieving total tumor removal.
