Craniopharyngioma is a common benign tumor of embryonic residue in the saddle area, but it has long been one of the difficulties in neurosurgical treatment due to its deep location, complex surrounding anatomy, close relationship with the hypothalamic pituitary axis, and easy recurrence after surgery. The optimal treatment strategy for craniopharyngioma is still under debate, but the view that total surgical resection of the tumor is the prerequisite and basis for a favorable prognosis while avoiding serious complications is recognized by most neurosurgeons. The transsphenoidal sinus approach was one of the first surgical approaches used to remove craniopharyngioma, which has the advantages of no brain tissues to be stretched, high safety, significant decompression of the optic nerve, and low endocrine impact, but its application is limited by the small surgical field, high incidence of cerebrospinal fluid leakage, and difficulty in resection of the suprasellar portion. However, due to the small surgical field of view, high incidence of cerebrospinal fluid leakage, and difficulty in resection of the suprasellar portion, it has become a supplementary access for surgical resection of craniopharyngioma. In recent years, with the advancement of surgical instruments, the application of new technologies such as neuroendoscopy and neuronavigation, and the development of expanded transsphenoidal surgical approach, the transsphenoidal sinus approach has become one of the most desirable surgical approaches for the treatment of craniopharyngioma. Craniopharyngioma origin, growth pattern and clinical staging The site of origin of craniopharyngioma, the growth pattern and the relationship with the optic cross, pituitary stalk and the base of the third ventricle are important references for choosing the surgical approach. It is generally believed that craniopharyngioma originates from the remnant cells of the degenerated craniopharyngeal duct, therefore, the tumor can originate from the anterior part of the third ventricle, the saddle, the suprasaddle, the pterygoid sinus and even the posterior wall of the nasopharyngeal cavity. The growth pattern of craniopharyngioma is often related to the site of origin of the tumor. Clinically, it is found that craniopharyngioma of subsaddle diaphragm origin grows upward partially restricted by the saddle diaphragm and the presence of subarachnoid space. As the tumor keeps growing upward to the saddle, the suprasaddle structures such as optic cross, pituitary stalk, and the floor of the third ventricle are pushed and displaced by the tumor, and the adhesion of the tumor to these important structures is often not heavy. If the tumor crosses the foramen of the saddle diaphragm and develops suprasellarly, it may form a tumor with a “girdle sign” pattern. Craniopharyngioma originating from the saddle diaphragm is more heavily adherent to the hypothalamic-pituitary axis, and because the tumor is not limited by the saddle diaphragm, it can develop in any direction, and the tumor shape is variable. Craniopharyngioma of the third ventricle may originate from the third ventricle alone or may be of intra- or supra-saddle origin pushing upward into the base of the third ventricle or breaking through the base of the third ventricle and entering the ventricle. Hoffman et al. classified craniopharyngiomas into intra-saddle, preoptic (tumor growing forward, pushing the optic chiasm and anterior cerebral artery upward and backward), and postoptic based on the relative relationship between the tumor and the saddle diaphragm, the optic chiasm, and the floor of the third ventricle. Sammi et al. classified craniopharyngiomas into four grades according to the degree of suprasellar growth, grade I intra-saddle or subsaddle diaphragm, grade II into the suprasellar brain pool with or without invasion of the saddle, grade III tumor invasion into the lower half of the third ventricle, and grade III tumor invasion into the third ventricle. Grade IV invades into the superior half of the third ventricle, and Grade V invades into the pellucid septum or into the lateral ventricles. In the 1960s, with the improvement of Hardy’s technique of transsphenoidal approach and the application of surgical microscope, the transsphenoidal approach was widely used for the surgical treatment of pituitary adenoma, craniopharyngioma, Rathke’s cyst and other tumors in the saddle area, which has the advantages of low strain on the brain tissue, adequate decompression of the optic nerve, low endocrine interference, safety, rapid postoperative recovery, and low mortality. It has the advantages of less strain on brain tissue, adequate decompression of the optic nerve, less endocrine interference, safety, rapid postoperative recovery, and low operative mortality and disability. However, the application of standard transsphenoidal surgery in the surgical treatment of craniopharyngioma is limited by the narrow surgical access, poor exposure of suprasellar structures, and the tendency of postoperative cerebrospinal fluid leakage. Most authors agree that standard transsphenoidal surgery is suitable for total resection of craniopharyngioma originating from the saddle because in this condition, the tumor growth is limited by the saddle septum, and the upper surface of the tumor is completely enveloped by the enlarged saddle septum, and there are often no obvious adhesions between the tumor and the surrounding and hypothalamic structures, which can be easily pulled down for total resection during the surgery. In contrast, because of the lack of growth resistance around the suprasellar craniopharyngioma, the tumor tends to grow into the surrounding brain pool and the third ventricle, with irregular shape, such as finger-like invasion of the brain parenchyma, serious adhesions with the surrounding vascular nerves, easy to calcify, and difficult to be removed by transsphenoidal sinus surgery. There are several aspects to be considered in the screening of craniopharyngioma cases by standard transsphenoidal approach: (1) According to the craniopharyngioma typing, tumors originating from the subsaddle septum in the saddle are more suitable for this procedure. (2) Tumor cystic change Tumor parenchymal part is located in the saddle and suprasellar cystic change is also suitable for transsphenoidal surgical resection, but total resection is difficult if the suprasellar cystic wall is heavily adhered. (3) Tumor development direction The standard transsphenoidal surgical exposure is mainly for the limited midline structures in the saddle area of the skull base, if the tumor grows obviously to the lateral side, the standard transsphenoidal surgical resection is difficult. (4) Patients who are in poor general condition and cannot tolerate craniotomy can have their tumors partially removed by transsphenoidal resection to relieve clinical symptoms. In some recurrent cases, transsphenoidal sinus surgery can be considered as the first treatment. The surgery is performed by using the standard transoral nasopterygoid sinus or single nasopterygoid sinus approach. The dura mater of the saddle base is incised, and the anterior pituitary tissue, which is mostly found to be compressed into a thin sheet, located in front of or below the tumor, is sharply incised to expose the tumor, and the sharp incision of the pituitary tissue does not aggravate the functional impairment of the pituitary gland. After the cystic fluid is extracted by puncture, the tumor envelope is cut open and the tumor is removed in pieces by entering the tumor. Careful identification of the site of origin of the craniopharyngioma, most commonly the saddle diaphragm and pituitary stalk, are often heavily adherent and require sharp separation to facilitate total resection, while protection of the pituitary stalk should be emphasized.Maira et al. reported a transsphenoidal sinus-saddle diaphragm approach to resect suprasellar craniopharyngiomas, further expanding the indications for the standard transsphenoidal approach, which requires dissection of the pituitary gland and saddle diaphragm to expose and resect This procedure is suitable for cases in which the tumor is located behind the optic chiasm and is accompanied by the anterior optic chiasm and the anterior cerebral artery complex anteriorly, which are difficult to resect either by the inferior frontal approach or by the pterygoid approach. Expanded Transsphenoidal Approach In 1987, Weiss reported the first successful microscopic resection of a craniopharyngioma previously thought to be suitable only for craniotomy using an expanded transsphenoidal approach, and in the following years, authors continued to report successful treatment of craniopharyngiomas in the suprasellar and third ventricle using this modified transsphenoidal approach. The expanded transsphenoidal approach offers all the advantages of transsphenoidal surgery, and at the same time, the expanded transsphenoidal approach provides a way to reach the suprasellar region without pulling the brain tissue, allowing the surgeon to remove the tumor through the anatomical gaps such as supraoptic, infraoptic, and left and right pituitary stalk, greatly reducing the probability of damage to the surrounding normal brain tissue, nerves, and other important structures, and reducing the occurrence of serious postoperative complications. The most important and difficult step of surgical resection for craniopharyngioma is the removal of the adhesions between the tumor origin and the hypothalamic pituitary axis. The location under the optic cross in the saddle during craniotomy is often a dead end of surgery and difficult to expose, while this area is precisely the part where the tumor is most likely to originate clinically. The direction of the enlarged transsphenoidal surgical approach is from anterior inferior to posterior superior, and after reaching the optic cross pool, the tumor can be resected through the supra-optic cross-end plate approach or inferior optic cross approach according to the growth pattern of the tumor and the position of the optic cross, the direction of the surgical approach is basically the same as the direction of the tumor growth, especially the inferior optic cross approach can directly observe the inferior optic cross structure, which eliminates the dead angle of exposure in craniotomy and resects the tumor under direct vision. It can also protect the integrity of hypothalamic pituitary axis, reduce the incidence of serious postoperative complications, and reduce the residual tumor. In general, the expanded transsphenoidal approach can be used for most types of craniopharyngioma, but if the tumor develops in the posterior direction or grows in the third ventricle, the transsphenoidal superior-endplate approach or a combination of these two approaches should be considered for tumor resection. When the anterior wall of the pterygoid sinus is resected, the posterior septal sinus should be resected at the same time. The extent of saddle base bone resection includes the saddle tuberosity and part of the posterior pterygoid plateau in the forward direction and the slope in the backward direction, and the saddle tuberosity should be resected horizontally to the sides to reach the medial edge of the optic nerve at the entry of the optic canal. Dissection of the dura at the saddle tuberosity often requires treatment of the cricoid sinus prior to dissection to prevent uncontrollable hemorrhage. A longitudinal straight incision or Y-shaped incision of the dura is made to fully expose the suprasellar structures. If the tumor develops in front of the optic cross, the optic cross and anterior cerebral artery complex are displaced by the tumor pushing upward, the tumor envelope can be directly observed after incision of the arachnoid, and there is enough space for resection of the tumor in pieces, if the tumor develops behind the optic cross, the optic cross and anterior cerebral artery complex are located in front of the tumor, which affects the space for tumor resection to some extent, but after decompressive resection under the optic cross, the operation space will be gradually increased. It will gradually increase, but in some cases where the tumor develops toward the third ventricle, the third ventricle can be exposed via the superior-terminus plate of the optic cross and the tumor can be resected, and careful protection of the anterior cerebral artery and anterior communicating artery should be paid attention to during this process. The greatest advantage of the expanded transsphenoidal surgery is that it allows the operator to observe the tumor’s origin location on the hypothalamic pituitary axis under direct vision again, which can maximize the sharp excision of the closely adherent part of the tumor and hypothalamic pituitary axis and protect the normal neurovascular anatomy. Compared with traditional transsphenoidal surgery and craniotomy, expanded transsphenoidal surgery under the microscope exposes the tumor more directly and adequately, utilizes the normal anatomical gap for surgical operation, and reduces the occurrence of surgery-related canal injury. However, its field of view is still mainly midline structures, and tumors that develop laterally are difficult to resect, and the surgical path is deep and narrow, which is also a challenge for the operator to operate. In recent years, with the maturation and development of new technologies such as neuroendoscopy and neuronavigation, more and more operators are willing to use endoscopic extended transsphenoidal surgery to remove tumors in the saddle area. Since intraoperative navigation and positioning techniques can be combined with the use of multi-angle endoscopy for operative field observation, the safety of the operation is further improved and the indications for expanded transsphenoidal surgery are also further expanded. The endoscope was first used as an auxiliary device for microscopic extended transsphenoidal surgery to observe whether there was residual tumor after resection, and if residual tumor was found, the endoscope was removed and microscopic resection was continued. The procedure does not require operation under the mucosa of the nasal septum, but only requires occlusion of part of the bony root of the nasal septum and the ventral wall of the pterygoid sinus, and does not require intraoperative retractor placement. Of course, neuroendoscopic techniques also have disadvantages, such as only providing two-dimensional images and some distortion of the images, which can be overcome with operator experience. Repair of cerebrospinal fluid leaks during transsphenoidal surgery Postoperative cerebrospinal fluid leaks are more common in cases of transsphenoidal craniopharyngioma resection, due to the growth characteristics of the tumor and the surgical approach. In standard transsphenoidal sinus surgery, gelatin sponge, artificial dura, fat, muscle, and fascia are mostly used to repair the leak and reconstruct the saddle base with the aid of bioadhesive, and most of the results can be achieved. In the case of extended transsphenoidal surgery, due to the wide range of saddle bone resection and large dural incision, it is very difficult to perform dural repair and saddle base bone reconstruction, and the incidence of cerebrospinal fluid leakage is higher after surgery. Masahiko Kitano and Mamoru Taneda reported a double-layer patch made of polytetrafluoroethylene (ePTFE) and autologous fascia to prevent postoperative cerebrospinal fluid leakage after extended transsphenoidal approach. The repair was performed with hydroxyapatite bone cement and the saddle base was reconstructed with satisfactory results, and none of the 22 patients who underwent repair and reconstruction using this method had cerebrospinal fluid leakage after surgery. Transsphenoidal approach for craniopharyngioma has the advantages of less trauma, faster recovery, significant decompression of the optic nerve, and less impact on endocrine, etc. At the same time, combined with the expanded transsphenoidal approach and advanced equipment and techniques, craniopharyngioma, which was previously thought to be treated only by craniotomy, can be completely resected in a safer and more effective surgical way. Therefore, selecting a suitable case and treating craniopharyngioma with a transsphenoidal approach is an ideal treatment method to obtain the desired result with minimal risk, which is the embodiment of the minimally invasive concept.