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.
