[Expanded Endoscopic Endonasal Surgery for Skull Base Tumors].

With the development of endoscopic and surgical instruments, expanded endoscopic endonasal surgery for skull base tumors has been widely performed. Compared with conventional microscopic transsphenoidal surgery, endoscopic surgery provides a wider view and clearer images, owing to the introduction of a high-resolution camera. However, for safe and reliable surgery, it is necessary to create an appropriate surgical field and avoid complications. This article discusses the basic knowledge needed for expanded endoscopic endonasal surgery, focusing on surgical anatomy and techniques and how to close the skull base completely.

Fascia patchwork closure for endoscopic endonasal skull base surgery.

With the development of endoscopic technology and surgery, resection of midline skull base tumors has been achieved using endoscopic endonasal skull base (EESB) approaches. EESB approaches reportedly have a greater risk of postoperative cerebrospinal fluid (CSF) leakage. Recently, the introduction of the nasoseptal flap (NSF) decreased dramatically the incidence of CSF leakage, but the use of an NSF increases the risk of disturbing the function of the nose. Here, we report our new technique called "fascia patchwork closure" for closure after EESB surgery and its outcome. All 48 cases involved midline skull base tumors resected via EESB approaches. Of them, 32 cases were closed by the fascia patchwork technique after tumor resection, and there was no incidence of CSF leakage. Moreover, 6 of the 32 cases were closed without the use of an NSF, indicating that the fascia patchwork closure approach is effective as part of a multilayer closure for the prevention of CSF leakage. The establishment and popularization of this technique might result in the further development of EESB surgery and also an improvement of postoperative nasal function.

Endocan, a new invasion and angiogenesis marker of pituitary adenomas.

Angiogenesis plays a crucial role in tumor growth. Recently, endocan has emerged as a new marker of vascular endothelial cells from cancers in other organs. In this study, we elucidated the relationship between endocan expression and tumor invasion of pituitary adenoma. Tumor tissues were obtained from 70 patients with pituitary adenoma and were examined using fluorescence immunohistochemistry. Tissue samples included 4 adrenocorticotrophic hormone producing adenomas, 10 growth hormone-producing adenomas, 49 clinically nonfunctioning adenomas, 6 prolactin producing adenomas, and 1 thyroid-stimulating hormone producing adenoma. Endocan was exclusively expressed in CD34-positive vascular endothelial cells, with over 90 % colocalization. The CD34 expression was significantly elevated with endocan expression (linear regression slope, 1.200; r(2) = 0.268, F = 23.08, p < 0.0001). As a percentage of CD34 expression, endocan expression was elevated in a Knosp grading dependent manner (Spearman's r-value, 0.651; p < 0.0001), and was also significantly elevated in macroadenomas compared with microadenomas (p = 0.0133). However, no differences in endocan expression were observed between hormonal subtypes (p = 0.066; Kruskal-Wallis test), age (Spearman's rank correlation test, p = 0.4909), or sex (Mann-Whitney test, p = 0.1701). These data show that endocan is closely related to tumor angiogenesis, and may predict tumor invasion into neighboring cavernous sinuses in pituitary adenomas.

Molecular status of pituitary carcinoma and atypical adenoma that contributes the effectiveness of temozolomide.

There have been several reports of temozolomide (TMZ) treatment of pituitary carcinomas and atypical adenomas. O(6)-methyl-guanine-DNA methyltransferase is not the sole molecule determining the sensitivity to TMZ in pituitary carcinomas and atypical adenomas. The Japan Society of Hypothalamic and Pituitary Tumors study suggests that MSH6, one of mismatch repair pathway enzyme, fulfills a contributory role to the efficacy of TMZ treatment for pituitary carcinomas and atypical adenomas. The preserved MSH6 function might be essential for the responsiveness to TMZ treatment in pituitary carcinomas and atypical adenomas.

Assessment of pre- and postoperative endocrine function in 94 patients with Rathke's cleft cyst.

We reviewed 94 patients with Rathke's cleft cyst (RCC) who were surgically treated at Nippon Medical School Hospital between December 1995 and July 2009 to clarify the effect of surgery on their endocrine function. In our statistical analysis we considered their age and sex, the cyst volume, and preoperative MRI findings. Using simple linear- and multiple regression analysis we evaluated the association between these factors and their preoperative hormone baseline levels. To assess pre- and postoperative anterior pituitary function we subjected the results of various hormone loading tests to the Wilcoxon rank sum test. Surgery improved headache and visual impairment in most patients and elevated PRL levels were significantly normalized after surgery (p = 0.004). However, pre- and postoperative anterior pituitary hormone loading tests revealed that the levels of GH, TSH, LH, and FSH were not improved significantly by surgery. Although the ACTH loading test showed postoperative improvement, the change was not statistically significant. We suggest that RCC patients with headache or visual impairment are good candidates for surgery. We also recommend that patients with hyperprolactinemia and those with ACTH deficiency whose MRI findings reveal low-intensity on T1WI and high-intensity on T2WI are likely to benefit from surgery. In contrast, RCC patients with other hormone dysfunctions do not appear to benefit from surgical intervention.

Optimal Multiple-Layered Anterior Skull Base Reconstruction Using a 360° Suturing Technique.

BACKGROUND: Advances in technique and instrumentation have improved outcomes after resection of anterior skull base tumors. However, cerebrospinal fluid (CSF) leak occurs in 4%-20% of patients. To reduce the risk of CSF leak, we have developed a novel reconstruction technique that consists of a 4-layered graft with patchwork suturing and hard material. OBJECTIVE: To evaluate the effectiveness of this reconstruction technique when used for resection of anterior skull base tumors. METHODS: This case series included 59 patients with anterior skull base tumors in whom the 4-layered closure technique was used. The main outcome measures were complications, including CSF leak, meningitis, postoperative bleeding, and infection. RESULTS: There were no CSF leak cases or serious complications after closure of the anterior skull base using the 4-layered technique. CONCLUSION: Closure of the anterior skull base in 4 layers prevented CSF leak and was not associated with any serious complications. However, further studies in larger numbers of patients are needed to confirm our outcomes using this closure method.

Easy slip-knot: a new simple tying technique for deep sutures.

BACKGROUND: Knot-tying in the deep operative field is very complicated because of the narrow working space during endoscopic transsphenoidal surgery. We present a novel technique for tying deep knots called the "easy slip-knot," which was developed from a knot used to tie fishing lines. METHOD: After threading the dura, an easy slip-knot is made outside the nostril. One end of the string is pulled, the knot then naturally slips, and should reach the operative field without needing a knot-pusher. FINDINGS: This method is not complicated, is easily applied to the operative field by slipping the knot into position, and is able to tie sutures securely. CONCLUSIONS: The easy slip-knot should be useful for endoscopic surgery.

Advanced Endoscopic Endonasal Approach to the Pterygopalatine Fossa and Orbit: The Endoscopic Tri-port Approach.

Objective The pterygopalatine fossa (PPF) is a narrow space situated posterior to the maxillary sinus. While external approaches have been used to treat tumors of the PPF, recent endoscopic approaches have become favored as an alternative; we developed an endoscopic tri-port approach, which provides wide surgical corridor with minimal invasion, for PPF. This report aims to introduce and verify the new approach. Design Case series. Setting A tertiary referral hospital. Participants We reviewed 11 patients with PPF or orbital tumors who were treated with the endoscopic tri-port approach. Main Outcome Measures Accessing tri-port approach's effects and limitations. Results When the tumor was located in the PPF or orbit without intracranial invasion, en bloc resection was achieved in six patients. With the exception of one patient, the nasal septum was preserved if not used for skull base reconstruction. If not invaded by a tumor or necessary for reconstruction, the inferior and middle turbinates were preserved. Conclusion The endoscopic tri-port approach provides an excellent surgical view and wide corridor and not requires an external approach, including a gingival incision.

Immunohistochemical detection of somatostatin receptor (SSTR) subtypes 2A and 5 in pituitary adenoma from acromegalic patients: good correlation with preoperative response to octreotide.

OBJECTIVE: The aim of this study was to determine the correlation between the expression of somatostatin receptors by immunohistochemistry and the percent suppression of GH levels in the octreotide suppression test. PATIENTS AND METHODS: Twenty-two patients with acromegaly who underwent an octreotide suppression test before surgery were studied. We performed immunohistochemistry for Somatostatin receptor 2A (SSTR2A) and Somatostatin receptor 5 (SSTR5) on the surgical specimens from all patients, which we scored according to the number of tumor cells staining positive at the surface membrane (3+: >50%, 2+: 25-50%, 1+: <25%). We sought correlations of percent suppression in the octreotide suppression test with these immunohistochemistry scores. RESULTS: Somatostatin receptor 2A (SSTR2A) showed the highest frequency of score 3+ (13 of 22, 59.1%) by immunohistochemistry. Subtype 5 showed the highest frequency for score 2+ (9 of 22, 40.9%), and one (4.5%) was immunonegative. For subtype 2A, there was a significant correlation with percent decrease (P = 0.002 < 0.01). In contrast, there was no significant correlation for SSTR5. CONCLUSION: Immunohistochemistry for SSTR2A in pathology specimens from acromegalic patients enabled selection of those experiencing clinical benefit from octreotide. Therefore, performing immunohistochemistry for detection of SSTR2A is recommended for all specimens obtained by surgery.

Surgical Anatomy for the Endoscopic Endonasal Approach to the Ventrolateral Skull Base.

The authors describe the surgical anatomy for the endoscopic endonasal approach (EEA) to the ventrolateral skull base. The ventrolateral skull base can be divided into two segments: the upper lateral and lower lateral skull base. The upper lateral skull base includes the cavernous sinus and the orbit, while the lower lateral skull base includes the petrous apex, Meckel's cave, parapharyngeal space, infratemporal fossa, etc. To gain access to the upper lateral skull base, a simple opening of the ethmoid sinus provides sufficient exposure of this area. To reach the lower lateral skull base, a transpterygoid approach, following ethmoidectomy, is a key procedure providing wide exposure of this area. Understanding of surgical anatomy is mandatory for treating ventrolateral skull base lesions via EEA. An appropriate, less-invasive approach should be applied depending on the size, location, and type of lesion.

Immunonegative "null cell" adenomas and gonadotropin (Gn) subunit (SUs) immunopositive adenomas share frequent expression of multiple transcription factors.

The differentiation of pituitary cells and human pituitary adenomas follow three cell lineages: GH-PRL-TSH, ACTH, and FSH/LH, which are regulated by a combination of various transcription factors and co-factors. We have used RT-PCR and immunohistochemistry to show that immunonegative, "null cell" adenomas are equipped with multiple transcription factors and co-factors. The "null cell" adenomas showed similar frequencies of transcription factors as did the gonadotropin subunit (GnSU)-positive adenomas, with the exception that there were fewer instances of SF1 in the former. We speculate, therefore, that null cell adenomas and GnSU-positive adenomas share common molecular mechanisms in functional differentiation, even though the former do not produce hormones. From the high frequency of various transcription factors, we also speculate that both null cell adenomas and GnSU-positive adenomas are derived from "committed" pituitary progenitor stem cells. The questions, why a certain proportion of these pituitary tumor groups lack hormone production and why they are molecularly more committed to Gn transcription, remain to be further investigated.

Gremlin, a bone morphogenetic protein antagonist, is a crucial angiogenic factor in pituitary adenoma.

Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005, r (2) = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells.

Endoscopic transsphenoidal cisternostomy for nonneoplastic sellar cysts.

Background and Importance. Sellar arachnoid cysts and Rathke's cleft cysts are benign lesions that produce similar symptoms, including optochiasmatic compression, pituitary dysfunction, and headache. Studies have reported the use of various surgical treatment methods for treating these symptoms, preventing recurrence, and minimizing operative complications. However, the postoperative cerebrospinal fluid (CSF) fistula and recurrence rate remain significant. Clinical Presentation. In this paper, we present 8 consecutive cases involving arachnoid cysts and Rathke's cleft cysts, which were managed by using drainage and cisternostomy, the intentional fenestration of the cyst into the subarachnoid space, and then meticulously closing sellar floor using dural sutures. The postoperative images, CSF fistula rate, and the recurrence rate were favorable. Conclusion. We report this technique and discuss the benefit of this minimally invasive approach.

Sellar Chondroma with Endocrine Dysfunction that Resolved after Surgery: Case Report.

Chondromas originating from the sella turcica are rare, and the most common initial symptoms are headache and visual disturbance. We describe a case of sellar chondroma with endocrine impairment as an initial manifestation that completely resolved after surgery. A 40-year-old Japanese woman with amenorrhea and galactorrhea for the last 2 years was referred to our department of neurosurgery for the evaluation of high prolactin levels and a tumor in the sella turcica. A biochemical assessment indicated endocrine dysfunction. Magnetic resonance imaging and computed tomography indicated a tumor in the sella turcica. The patient's presentation favored the preoperative diagnosis of pituitary adenoma or Rathke's cleft cyst. However, because calcification was detected, other types of tumors, such as craniopharyngioma, meningioma, and chordoma, were also considered. Endoscopic transsphenoidal surgery was performed, and the possibility of a bony tumor was recognized. Finally, the tumor was completely removed, and the histopathological findings confirmed chondroma. The postoperative course was uneventful, and endocrine function improved. Five years after surgery, the patient is doing well without pituitary insufficiency, pituitary hormone medications, or signs of tumor recurrence. In cases of sellar chondroma, endocrine dysfunction sometimes precedes other symptoms, such as headache and visual disturbance. When examining a patient with an intrasellar tumor harboring calcification, clinicians must consider the possibility of sellar chondroma. Furthermore, to the best of our knowledge, this case is the first of sellar chondroma treated with endoscopic surgery to be reported.

Pulsed Laser-induced Liquid Jet System for Treatment of Sellar and Parasellar Tumors: Safety Evaluation.

OBJECTIVE: The pulsed laser-induced liquid jet (LILJ) system is an emerging surgical instrument intended to assist both maximal removal of the lesion and functional maintenance through preservation of fine vessels and minimal damage to the surrounding tissue. The system ejects the minimum required amount of pulsed water through a handy bayonet-shaped catheter. We have already shown a significant increase in removal rate, in addition to a noteworthy reduction of intraoperative blood loss and procedure time in the treatment of large pituitary and skull base tumors in a single-institution series. The present study evaluated the safety of the system in multiple institutions. METHODS: The study included 46 patients, 29 men and 17 women (mean age: 59.1 years) who underwent microsurgical/endoscopic resection of lesions in or in the vicinity of the pituitary fossa through the transsphenoidal approach between October 2011 and June 2012 at six institutions. The histologic diagnoses were pituitary adenoma (31 cases), meningioma (4), craniopharyngioma (3), cavernous angioma (2), and Rathke cyst cleft (1). Lesion volume ranged from 2.0 to 30.4 cm³ (mean: 3.7 cm³). Cavernous sinus invasion was observed in 11 cases and suprasellar extension in 29 cases. RESULTS: Preservation of intralesional arteries (diameter: 150 µm) was achieved in all situations in > 80% of cases. Intended surgical steps were achieved except for some restrictions in motion due to the use of an optical quartz fiber. No complications occurred directly related to the use of the device. CONCLUSIONS: The LILJ system can be used for safe removal of lesions in or in the vicinity of the pituitary fossa.

Vascular networks and endothelial cells in the rat experimental pituitary glands and in the human pituitary adenomas.

There has been considerable interest in the relationship between hormone-secreting endocrine cells (HSEC) and their microvessels (MVN) in human pituitary gland. However, microcirculatory networks have rarely been studied in three dimensions (3D). Therefore, this study was designed to visualize and to reveal the relationship between hormone secreting endocrine cells and their microvessel environment including vascular endothelial cells in 3D using rat pituitary glands under various experimental conditions by confocal laser scanning microscopy (CLSM). By CLSM, the 3D distributions of MVN were visualized and revealed a relationship between HSEC and MVN in experimental pituitary glands and human pituitary adenomas. Therefore, 3D reconstructed imaging by CLSM is a useful technique with which to investigate the microvessel environment of hormone-secreting cells and has the potential to reveal dynamic hormone-secreting pathways.