一、Project basis The pseudocapsule was first described by Costello in the early 1900s,
which was formed by the compression between the tumor and normal gland. Adenoma growth
leads to compression of the acinar structure of the adjacent normal gland, resulting in a
reticulin-rich pseudocapsule that encases the entire adenoma in. Over the last two
decades, the endoscopic endonasal approach (EEA) has been extensively developed and
refined for the resection of pituitary adenomas (PAs). The endoscopic panoramic view is
superior in terms of efficacy and safety for sellar surgery, and studies have reported
that PAs can be effectively resected by EEA with minimal postoperative morbidity.
Oldfield and colleagues used the phrase "surgical capsule of adenoma" to describe the
histologically confirmed pseudocapsule in 2006 which was found in about 50% of patients
and tends to be more frequent in larger tumors. The studies elaborated procedure along
the outer face of the pseudocapsule between the adenoma and surrounding normal gland
tissue achieved radical removal of the tumor while preserving normal pituitary function.
Thus, in recent years, extracapsular resection (ER), which emphasized the importance of
pseudocapsule as a surgical plane, was adopted for more radical resection of the tumor.
In smaller tumors, the pseudocapsule tended to exist more prominently and to cover the
whole tumor, whereas in larger tumors the pseudocapsule tended to be discontinuous or
disrupted. Similarly, in the present study, investigators found that ER was more
performed in microadenomas, whereas intracapsular resection (IR) was more adopted in
macroadenomas. Furthermore, in some macroadenomas, the pseudocapsule could not be seen
until proper intracapsular debulking. By contrast, some PAs exhibited no or undefinable
pseudocapsule; during the entire procedure, the adenoma was excised piecemeal
progressively with a dissector, blunt ring curette, and aspirator.
Although PAs were frequently present within the pseudocapsule and complete tumor
resection using the ER technique has been reported to maximize the effectiveness for PAs
with pseudocapsules, many authors believe that resection without compromising pituitary
function is imperative to improving the ultimate health outcome of patients. In some
selective cases, an incomplete adenoma resection is advised because it is expected that
this is best for the patients, through lower complication rates and preserving pituitary
function. The actual effects of ER-based complete resection of PA are still under debate.
Intact pituitary gland function is deemed more important than adenoma total removal,
Theoretically, it is hard for surgeons to extirpate only tumor cells completely during
surgery without removing any normal pituitary gland tissue because in most cases the
adenoma directly contacts with the normal pituitary gland. Some scholars found that the
capsule itself contains tumor cells and may be a main cause of persistent hypersecretion
of the hormone and possibly the source of recurrence. In addition, some studies found
that the pseudocapsule is disrupted by tumor invasion so that the extracapsular removal
and management of tumor invasion outside of the pseudocapsule are crucial to
accomplishing complete PA removal. For these refractory pituitary adenomas, some research
recommend aggressive resection, especially in IR resection cases. Partial gland resection
or resection of the cavernous sinus medial wall is necessary in some cases since studies
showed that it could help improve biochemical remission for the pituitary gland.
Pseudocapsule-Based Resection for Pituitary Adenomas has become a hot topic in recent
years. However, it often focuses on the influence of pituitary function after surgical
resection and the management and evaluation of surgical complications. How to strengthen
the recognition of normal pituitary and pituitary pseudocapsule by imaging before
operation? How to combine preoperative image enhanced recognition of pseudocapsule during
operation? How to confirm the boundary between normal tissue and pituitary gland by
Intraoperative pathology? What kind of treatment strategy should be adopted for pituitary
adenomas of different sizes? There are few relevant reports on the above doubts.
Standardized operation for pituitary adenoma is also lack, even if it can reduce trauma
and complications; There are few studies on relationship among postoperative magnetic
resonance imaging and related endocrine function examination and the evaluation of
Extr-apseudocapsular resection for Pituitary Adenomas. It is urgent to establish a
biological sample bank of pituitary tumor.
二、Research Contents:
1. To identify the pituitary tissue and the pseudocapsule by preoperative imaging data.
2. To evaluate the significance of preoperative imaging by relationship between tumor
and pseudocapsule during operation.
3. To research the significance of intraoperative rapid pathology in excision of
pituitary tumor. 4. To establish Standardized surgical treatment strategies for pituitary tumors.
5. Postoperative imaging data and clinical endocrine function examination were used to
evaluate the surgical efficacy.
6. To establish biological sample bank of pituitary tumor.
三、Research method, technical route and work plan. 1. General Data and Clinical Manifestations In this retrospective study, investigators
will review patients in our and cooperation institutions (Department of
Neurosurgery, Affiliated Hospital of Nantong University, Jiangsu, China; Department
of Neurosurgery, Subei People's Hospital of Jiangsu province, China; Department of
Neurosurgery, The First People's Hospital of Changzhou, Jiangsu, China) who undergo
EEA for PAs. The information will collect from patients' electronic medical records
included presenting symptoms, operative notes, postoperative course,, laboratory
data. Informed consent will obtain from all patients.
2. Endocrinological Evaluations All patients undergo a baseline preoperative pituitary
hormone examination including serum cortisol, free thyroxine, thyroid stimulation
hormone (TSH), adrenocorticotropic hormone (ACTH), growth hormone (GH) and
insulin-like growth factor-1 (IGF-1), prolactin (PRL), luteinizing hormone (LH) and
follicle stimulating hormone (FSH), testosterone (in males), and estradiol (in
females). Postoperative biochemical remission will be defined as a nadir serum GH
level of 3,000 ml/day. Hormonal status will be evaluated at 1 week and 3 months
after surgery and twice per year thereafter to evaluate anterior pituitary
functions.
3. Imaging Analysis All patients undergo high-resolution magnetic resonance imaging
(MRI) examination before operation, within 3 days, 3 months, 6 months, and twice per
year after surgery. The distribution and density of the pituitary gland could be
seen on T1-weighted MR images. The position of the anterior communicating artery and
internal carotid artery could be seen on T2-weighted images, also enabling us to
reduce the surgical risks. Computed tomography is useful for demonstrating the
degree of pneumatization and locations of septations in the sphenoid sinus. The
degree of resection was calculated by measuring the residual tumor volume using MRI
data. The magnetic resonance imaging (MRI) scanning was performed before surgery to
provide excellent details about the tumor's size and texture, especially to
distinguish the boundary between the location of normal adenohypophysis and
pseudocapsule.
4. Pathological Examinations All resected tumor tissues were evaluated by routine
pathological and immunohistochemical examination. The composition of complete and
fragmentary pseudocapsules was pathologically examined. All tissues obtained in the
study were paraformaldehyde fixed and paraffin embedded. The sections were stained
using hematoxylin and eosin staining or Masson's trichrome staining.
Intact pituitary gland function is deemed more important than adenoma total removal,
Theoretically, it is hard for surgeons to extirpate only tumor cells completely
during surgery without removing any normal pituitary gland tissue because in most
cases the adenoma directly contacts with the normal pituitary gland.To minimize the
impact on pituitary functions, the suspicious tissue was sent to the pathology
department for histopathology intraoperatively.
5. Treatment strategies for different types of pituitary tumors Non-function pituitary
adenoma, PRL, GH, ACTH. 6. Depending on different tumor sizes and pseudocapsule development, investigators
adopted different resection strategies.
In microadenoma, the exposed surface of the pituitary gland looks completely normal; a
small cut was made in the gland at the location where the adenoma is expected according
to preoperative imaging. The right dissector was used to separate the tumor and to
preserve the integrity of the pseudocapsule, and achieved total extracapsular resection.
Usually, the microadenoma texture is soft, limiting the option of extracapsular
dissection. With small ring curettes, the tumor is removed and the tumor cavity was
explored meticulously.
For macroadenomas, no attempt is made to remove the entire tumor or pull it forward
during the initial phases of the dissection. After the intracapsular tumor is debulked
and partially removed followed by a median-lateral or basal-superior order, the residual
tumor was separated carefully along the pseudocapsular interface.
If the pseudocapsule was not visible in the first stage, investigators used conventional
conservative intracapsular resection. Internal debulking was continued until
visualization of the pseudocapsule or cavernous sinus wall was achieved. Extracapsular
resection was continued along the plane, preserving as much integrity of the
pseudocapsule as possible.
After internal debulking, if the pseudocapsule was still unidentifiable, the adenoma was
excised piecemeal progressively. Noteworthily, investigators adopted intensive excision
and meticulous sweeping to remove small remnants that are hidden behind the fibrin
membranes for PA. The surface of the pituitary gland was peeled off as thin a slice as
possible, and the tumor bed was circumferentially resected to remove any small tumor
remnant in Cushing disease or acromegaly patients.
To minimize the impact on pituitary functions, the suspicious tissue was sent to the
pathology department for histopathology intraoperatively.
