The data collection for this study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University. We retrospectively collected data from 237 patients who underwent endoscopic transsphenoidal pituitary adenoma surgery by a single surgeon (ZDW) from 1/2017 to 8/2019. The data included a complete history, intraoperative observation, physical and neurological examinations, and radiological assessment.The distinction of the pseudocapsule is more difficult in tumors with a maximum diameter larger than 15 mm, according to the literature. To reflect the difference in surgical technique between microadenomas and macroadenomas, 192 patients (tumor largest diameter 15-40mm) were included in this study.
The exclusion criteria were as follows:
- patient had not undergone an MRI scan preoperatively or postoperatively (n=7)
- follow-up time <3 months (n=27)
- adenomas were intracranial extradural (Hardy D) as assessed according to the Hardy modification classification system (n=15).
Adenomas that were classified as Hardy D were excluded because the pseudocapsule only covers intrasellar tumor tissue, and complete resection of extradural tumor tissue inevitably leads to intraoperative leakage of cerebrospinal fluid (CSF), which will influence the analysis of surgical complications. Invasive tumors, Hardy E, Knosp 3 or 4, were not ruled out because these adenomas still covered by incomplete pseudocapsules possibly and the resection does not necessarily cause CSF leakage. Following application of the inclusion and exclusion criteria, we performed a statistical analysis on a total of 143 patients.
Images were retrospectively reviewed by the first authors (WZQ and LGH) to determine the tumor grade according to the Knosp and modified Hardy classification systems. The tumor volume was measured by Brainlab Systems
The location of the pituitary gland was identified by preoperative 3.0 T MRI and reconfirmed relying on Brainlab neuronavigation intraoperatively. surgeries were carried out using a standard binostril endoscopic approach (4 hand). In cases with a high risk of CSF leakage, a pediculate nasoseptal flap was harvested following the Hadad technique. The dura mater was opened widely, lateral to the cavernous sinus and superior to the tuberculum sellae, while attempting to leave the anterior surface of the pituitary (the pituitary capsule) intact.
Identification and establishment of the pseudocapsular surgical plane
In our study , the pseudocapsule was identified by dissecting dura mater, pituitary capsule, and pituitary gland.When there is no obvious pituitary capsule, we separate the tumor capsule and the pituitary gland from the inner side of the pituitary gland. This method is not fundamentally different from Taylor`s, which involves removing the tumor to expose the pituitary gland and establish a plane, however, in large pituitary adenomas, the pituitary tends to be on one sides of the tumor and is not always on the posterior side of the tumor. After the dura was opened, the anterior surface was inspected primarily using a disc dissector to determine the possible presence of the thin pituitary gland or capsule, which was excised to expose the pseudocapsule after it was identified. If the position was on the lateral surface of tumor and the anterior surface of the tumor was covered by an intact capsule-like tissue, surgeons decompressed the tumors and attempted to establish a pseudocapsular plane along the capsule from the pituitary side. If the position was located on the posterolateral/superior surface of the tumor or there was not a visible capsule covering the anterior surface of the tumor, the majority of tumor tissue was resected until the pituitary gland was exposed.
According to the presence of a pseudocapsular plane and its continuity that were determined by surgical videos, patients were divided into the following three groups: Group A (whole capsulectomy), Group B (partial capsulectomy) and Group C (piecemeal resection). Each patient was initially grouped and characteristics of pituitary adenomas such as CSF leakage, apoplexy and fibrosis were evaluated anonymously by two authors (WZQ and LGH), and then checked by the author (ZDW).
Among the 143 patient, 58(40.6%) patients (49 cases in Group A and 9 in Group B) had their pseudocapsules easily removed along with the main tumor mass.Thus, intraoperative biopsy of the removed capsule was not performed in these cases.For the remained patients who had found a distinguishable capsule-like tissue from the pituitary gland, a biopsy for frozen histopathological examination was performed on them.
1.En bloc capsulectomy
The pseudocapsular plane was kept clear, and its integrity was maintained during the whole excision process, which was defined as en bloc capsulectomy. In this fashion, surgeons could ensure that adenomas had been removed with the capsule completely. After separating the pseudocapsule from the pituitary gland, the tumor was supported using a disc dissector from the extrapseudocapsule to keep high tension at the interface. Meanwhile, using an aspirator to separate the pseudocapsule from peritumor tissue, all processes were performed under a clear operative field, which avoided injury to the pituitary gland as much as possible. When the resection was carried out to the posterolateral surface of the tumor, the tumor volume was decreased again to avoid crushing the thin capsule. （video1 part1）
In our study, surgeons tried to achieve a bloc resection to prevent the loss of the surgical plane, but there were 12 case patients. For the convenience of excision, the part of the adenoma that had been separated from the peritumor tissue was removed earlier during the resection process, but these parts were assigned to Group A.
2. Partial capsulectomy
Partial capsulectomy was performed when the pseudocapsular plane was lost. The common reasons for this loss included bleeding in the operating area, tumor fibrosis, tumor invading the cavernous sinus, bone or finding the pseudocapsule after piecemeal resection. Most pseudocapsules were thin and transparent, which made them hard to find again once the surgical plane was lost. Under this condition, piecemeal resection was used as a substitute to completely resect the residual tumor.
There were 9 case patients. The pseudocapsule was completely removed with the intrasellar adenoma, but the adenomas broke through pseudocapsules and invaded the cavernous sinus or bone, them was assigned to Group B.
3. Piecemeal resection
If no pseudocapsule was found during the operation or detected by pathology, the surgery was defined as piecemeal resection. The tumor was removed by a 2-suction technique. With a 30◦ rigid endoscope, we searched for residual tumors in hidden corners . After hemostasis of the tumor bed with oxidized cellulose, we sometimes applied a synthetic dural graft and a dural sealant. At the end of the procedure, silicone rubber implants and nasal packing were placed.
Assessment of Surgical outcome
The intraoperative observations included the integrity and characteristics of the pseudocapsule, adenomas texture, fibrosis, apoplexy, extent of adenomas invasion and intraoperative CSF leakage.
Most pituitary adenomas are soft , but some with a high collagen are sticky and Ceylan et al  showing that the fibrous composition of pituitary tumors is closely related to the aggressiveness of tumors, so adenomas fibrosis was roughly classified into two types (due to a lack of uniform standards[16,17]): 1) adenoma tissue was glutinous and some transparent and flimsy fibers could be observed and 2) the tumor was separated by white fibers or the white fibrous tissue adhered to the normal tissue. Type 1 adenomas were tumors with a high collagen content and without evidence of adherence to or invasion of surrounding tissue. Type 2 adenomas were separated by fibrous tissue or adhere to normal tissue tightly. Two cases of type 2 fiber tissue were resected with the capsule completely and placed into Group A (Fig 2). Adenoma apoplexy was judged according to surgical observations and preoperative MRI. Tumors that appeared to liquefy, coagulative necrotic tissue or black stale blood were identified as apoplexy. Inconspicuous hemorrhage of tumors was excluded from the statistics.
Postoperative pituitary function
New pituitary deficits were determined based on new laboratory deficiencies or treatment with new supplemental medications without previously documented deficiencies or supplemental medications. Patients with preoperative panhypopituitarism (n=7) were excluded from the evaluation of new-onset deficits after surgery. Patients with a prior abnormal pituitary deficit that returned to normal during follow-up, stopped supplemental medications or lacked clinical symptoms at follow-up were considered to have recovered from a preoperative pituitary deficiency.
All patients underwent a comprehensive endocrine evaluation within 3 days before surgery, 3 days before discharge, at 3 months and every 1–2 years after surgery. A 3.0 T MRI scan of the head was performed on the second day after surgery; at 3 months postoperatively, which was the criterion that was used to judge the gross total tumor resection (GTR) in each group; and thereafter every 1–2 years, as appropriate.
χ2 tests and Fisher exact tests for independence were used to determine the statistical significance of differences in Knosp type, adenoma type, surgical remission rate, GTR, CSF and postoperative pituitary function between groups. A multiple logistic regression model was estimated to study the relationship between categorical outcome variables and independent variables. The level of significance was set at p < 0.05. All calculations were made using the statistical software package IBM SPSS version 24.