[Normal Anatomy of the Pituitary Gland].

This study describes the anatomy of the pituitary gland during endoscopic endonasal surgery. Before surgery, the extent of pneumatization of the sphenoid sinus and bony septations in the sphenoid sinus should be evaluated using computed tomography. After wide sphenoidotomy, several important surgical landmarks, including the medial and lateral opticocarotid recesses and carotid protuberances, can be observed in the sphenoid sinus. The pituitary gland is composed of two components: the adenohypophysis and neurohypophysis. Two small vessels, the superior and inferior hypophyseal arteries, supply the pituitary gland. Several vital structures exist inside the cavernous sinus, including the internal carotid artery and cranial nerves. Understanding the surgical anatomy is mandatory for treating lesions around the pituitary fossa via the endoscopic endonasal approach.

A case of aggressive pituitary neuroendocrine tumour with extremely rapid progression: possible diagnostic value of TERT promoter methylation.

Most pituitary adenoma/neuroendocrine tumours (PitNET) are histologically benign and grow slowly; however, a subset of these tumours exhibit a more aggressive clinical course characterized by local invasiveness and early recurrence. These high-risk PitNETs often require multiple surgeries and radiation over several years and may eventually acquire carcinomatous characteristics, such as metastasis in some cases. Herein, we report a rare case of PitNET causing oculomotor paresis with extremely rapid recurrence only 3 months after initial surgery, followed by lethal liver metastasis. Preoperative magnetic resonance imaging and intraoperative findings were consistent with typical PitNETs, other than moderate invasion of the cavernous sinus. Pathological examination of the specimen obtained from the initial transsphenoidal surgery revealed increased mitosis and elevated rates of cells positive for Ki-67 and p53. Based on the immunohistochemical assessment for transcription factors and pituitary hormones, the diagnosis was determined to be a silent sparsely granulated corticotroph PitNET with focal malignant transformation. Aggressive features represented by Ki-67 and p53 positivity were more robust in recurrent and metastatic specimens, but hormone immunostaining was decreased. Epigenetic analysis revealed methylation of the telomerase reverse transcriptase (TERT) promoter in the tumour, resulting in TERT upregulation. Despite extensive research, markers for distinguishing extremely aggressive PitNETs have not been determined. Although further analysis is needed, our case demonstrates the possible usefulness of assessing TERT promoter methylation status in the stratification of recurrence risk in extremely high-risk variants of PitNET.

Effects of olive leaf powder supplemented to fish feed on muscle protein of red sea bream.

Olive leaf is known to have the high polyphenol content of 6-9% in dry weight. We investigated the effects of olive leaf powder (OLP) supplemented to fish feed on muscle protein of red sea bream (Pagrus major). Fish reared with feed containing 8% OLP for 40 days had 1.4 times higher myofibril content and 2.2 times higher acid-soluble collagen content than fish reared with control feed for the same period. On the other hand, sarcoplasmic protein content and collagenase activity of the muscle were almost the same between the control fish and OLP-diet fish. Microstructure observation of fish muscle showed that OLP-diet fish has more rigid endomysium structure than that of the control-diet fish. Since collagen fiber in endomysium is responsible for the texture of the muscle, feeding OLP to aquaculture fish will lead to a harder muscle texture. The present study suggests that OLP is a useful feed additive to enhance the texture of aquaculture red sea bream muscle through strengthening of the collagen structure in the muscle.

[A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis.

Endoscopic endonasal cranial base surgery simulation using an artificial cranial base model created by selective laser sintering.

Mastery of the expanded endoscopic endonasal approach (EEA) requires anatomical knowledge and surgical skills; the learning curve for this technique is steep. To a great degree, these skills can be gained by cadaveric dissections; however, ethical, religious, and legal considerations may interfere with this paradigm in different regions of the world. We assessed an artificial cranial base model for the surgical simulation of EEA and compared its usefulness with that of cadaveric specimens. The model is made of both polyamide nylon and glass beads using a selective laser sintering (SLS) technique to reflect CT-DICOM data of the patient's head. It features several artificial cranial base structures such as the dura mater, venous sinuses, cavernous sinuses, internal carotid arteries, and cranial nerves. Under endoscopic view, the model was dissected through the nostrils using a high-speed drill and other endonasal surgical instruments. Anatomical structures around and inside the sphenoid sinus were accurately reconstructed in the model, and several important surgical landmarks, including the medial and lateral optico-carotid recesses and vidian canals, were observed. The bone was removed with a high-speed drill until it was eggshell thin and the dura mater was preserved, a technique very similar to that applied in patients during endonasal cranial base approaches. The model allowed simulation of almost all sagittal and coronal plane EEA modules. SLS modeling is a useful tool for acquiring the anatomical knowledge and surgical expertise for performing EEA while avoiding the ethical, religious, and infection-related problems inherent with use of cadaveric specimens.

Growth stabilization and regression of meningiomas after discontinuation of cyproterone acetate: a case series of 12 patients.

BACKGROUND: The relationship between meningiomas and exogenous sex hormones is well known, but cyproterone acetate (CA), a progesterone agonist, seems to have a stronger influence on tumor growth. OBJECTIVE: To show the close relationship between CA treatment and meningioma growth. METHODS: Since 2010, all patients referred to our clinic for a suspicion of meningioma were questioned specifically about exogenous sex hormone intake and more specifically about CA intake. Twelve patients harboring one or multiple meningiomas and treated with CA were identified. CA was stopped in all cases. Tumor volumes and diameters were measured on serial MRIs and compared to the last MRI before CA withdrawal. RESULTS: Ten patients with multiple tumors had been taking the drug for a longer period of time (mean of 20.4 years) than the two patients with one tumor (10 years). Two patients with multiple tumors underwent surgery because of rapidly decreased visual acuity at the time of diagnosis. Discontinuation of CA led to tumor shrinkage in 11 patients and a stop in tumor growth in one [mean tumor volume reduction was around 10 cm(3)/year; range (0.00; 76)]. There was no regrowth during a mean follow-up period of 12 months (range: 5-35). CONCLUSION: For patients diagnosed with a meningioma and treated with CA, medication withdrawal followed by observation should be the first line of treatment. Care should be taken with long-term use of high doses of CA, and serial brain MRIs should be considered after several years of CA.

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts: technical note.

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke's cleft cyst (RCC). In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst. Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall. Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.

A handmade eye movement monitor using a piezoelectric device during transsphenoidal surgery.

We describe a handmade eye movement monitor featuring a piezoelectric device for use during transsphenoidal surgery (TSS). The sensor consists of a piezoelectric device, condensers, resistors, and several inexpensive parts. Eyeball movements elicited by surgical manipulations during TSS for cavernous sinus tumor are detected by small disc-shaped sensors taped to the eyelids. The responses could be monitored as sharp waves on an electroencephalograph. After we started using this monitor, both the incidence and the severity of cranial nerve injuries during TSS for cavernous sinus tumor decreased. Our device is especially useful at operations to remove functioning pituitary adenomas invading the cavernous sinus and contributes to their favorable endocrine outcomes. None of our patients manifested the postoperative swelling of the eyelids or conjunctival congestion generally seen in patients subjected to the insertion of needle sensors for the acquisition of electromyograms of the extraocular muscles, which is widely used during surgery to identify the cranial nerves responsible for eye movement. Our monitor is less expensive and easier to use than any commercially available sensor devices. As our method does not require the insertion of needle sensors, it is less invasive than electromyography of the extraocular muscles.

Anatomic comparison of the endonasal and transpetrosal approaches for interpeduncular fossa access.

OBJECT: The interpeduncular cistern, including the retrochiasmatic area, is one of the most challenging regions to approach surgically. Various conventional approaches to this region have been described; however, only the endoscopic endonasal approach via the dorsum sellae and the transpetrosal approach provide ideal exposure with a caudal-cranial view. The authors compared these 2 approaches to clarify their limitations and intrinsic advantages for access to the interpeduncular cistern. METHODS: Four fresh cadaver heads were studied. An endoscopic endonasal approach via the dorsum sellae with pituitary transposition was performed to expose the interpeduncular cistern. A transpetrosal approach was performed bilaterally, combining a retrolabyrinthine presigmoid and a subtemporal transtentorium approach. Water balloons were used to simulate space-occupying lesions. "Water balloon tumors" (WBTs), inflated to 2 different volumes (0.5 and 1.0 ml), were placed in the interpeduncular cistern to compare visualization using the 2 approaches. The distances between cranial nerve (CN) III and the posterior communicating artery (PCoA) and between CN III and the edge of the tentorium were measured through a transpetrosal approach to determine the width of surgical corridors using 0- to 6-ml WBTs in the interpeduncular cistern (n = 8). RESULTS: Both approaches provided adequate exposure of the interpeduncular cistern. The endoscopic endonasal approach yielded a good visualization of both CN III and the PCoA when a WBT was in the interpeduncular cistern. Visualization of the contralateral anatomical structures was impaired in the transpetrosal approach. The surgical corridor to the interpeduncular cistern via the transpetrosal approach was narrow when the WBT volume was small, but its width increased as the WBT volume increased. There was a statistically significant increase in the maximum distance between CN III and the PCoA (p = 0.047) and between CN III and the tentorium (p = 0.029) when the WBT volume was 6 ml. CONCLUSIONS: Both approaches are valid surgical options for retrochiasmatic lesions such as craniopharyngiomas. The endoscopic endonasal approach via the dorsum sellae provides a direct and wide exposure of the interpeduncular cistern with negligible neurovascular manipulation. The transpetrosal approach also allows direct access to the interpeduncular cistern without pituitary manipulation; however, the surgical corridor is narrow due to the surrounding neurovascular structures and affords poor contralateral visibility. Conversely, in the presence of large or giant tumors in the interpeduncular cistern, which widen the spaces between neurovascular structures, the transpetrosal approach becomes a superior route, whereas the endoscopic endonasal approach may provide limited freedom of movement in the lateral extension.

Salpingopharyngeus myomucosal flap.

OBJECTIVES: Improvements in the efficacy of extended endonasal approaches to resect skull base pathologies have created the need for new reconstructive alternatives. Hereby, we describe a novel pedicled myomucosal flap that allows the reconstruction of dural defects in the lower clivus and craniovertebral junction or to cover the paraclival and petrous segments of the internal carotid artery. STUDY DESIGN: Anatomic description. Technical report. Feasibility. METHODS: We describe a myomucosal flap with a cephalic pedicle based on the salpingopharyngeus muscle and its vessels. Subsequently, using a cadaveric model, we harvested the flap and explored its potential for the reconstruction of various dural defects or to cover the internal carotid artery. RESULTS: Our study confirmed the feasibility of harvesting and transposing the myomucosal salpingopharyngeus (Dicle flap) flap for the reconstruction of inferior clival and craniovertebral junction defects or to cover the petrous and paraclival segments of the internal carotid artery. CONCLUSIONS: The Dicle flap is a feasible, reconstructive alternative for the reconstruction of select small- to medium-sized defects of the posterior and inferior aspects of the ventral skull base.

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.

Chronic epidural hematoma with frontal skull-base destruction mimicking osteogenic tumor, associated with coagulopathy due to chronic hepatitis C.

Background: Intracranial epidural hematoma is generally evoked by acute coup-injury. Though rare, it has a chronic clinical course and can be a non-traumatic event. Case Description: The patient was A thirty-five-year-old man with a complaint of one-year history of hand tremor. He was suspected diagnosis of osteogenic tumor with differential diagnosis of epidural tumor, or abscess in the right frontal skull base bone, associated with chronic type C hepatitis because of his plain CT and MRI. Results: Results of examinations and surgery, the extradural mass was chronic epidural hematoma without skull fracture. We diagnosis he is the rare case of chronic epidural hematoma caused by coagulopathy due to chronic hepatitis C. Conclusion: We reported a rare case of chronic epidural hematoma caused by coagulopathy due to chronic hepatitis C. The repeated spontaneous hemorrhage in the epidural space formed the capsule and destruction of skull base bone, just mimicking skull base tumor.

Pathology of Crooke Cells in the Human Pituitaries: A Timely Review.

Crooke cell change was first found in the regressed and suppressed corticotroph (adrenocorticotropic hormone-producing) cells, and now is known to occur in pituitary tumors. The tumor cells of this type can be recognized by morphology with immunohistochemistry, and are well known to predict aggressive behavior such as invasion and rare metastases. This is one of the representative neuroendocrine tumors in the pituitary which is now considered to have malignant potential as proposed in the pancreas and gastrointestinal tracts. It is important to emphasize the pituitary tumor pathology such as Crooke cell change for prognostication and appropriate therapies. This review article describes the evolution from the Crooke cells to Crooke cell tumors which is timely along with the Fifth WHO classification 2022 published online.

Double pituitary neuroendocrine tumors in a patient with normal growth hormone level acromegaly: A case report and review of the literature.

Background: Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion caused by a pituitary neuroendocrine tumor (PitNET). However, some acromegaly patients show normal GH levels, and they can be a pitfall in clinical diagnosis. Moreover, rarely, synchronous true double or multiple PitNETs are encountered. Moreover, these PitNETs increase the risk of a left lesion during surgical exploration. Case Description: The patient, who was a 73-year-old female, was referred to our hospital with a chief complaint of headache. Assessment of basal anterior pituitary function revealed a slightly high level of insulin-like growth factor-1 (IGF-1) (standard deviation, 2.4), and her physical findings exhibited mild acromegalic features. The endocrine evaluation confirmed acromegaly and magnetic resonance imaging (MRI) showed a macro PitNET with suprasellar extension. Endoscopic endonasal surgery (EES) was performed to remove the macro PitNET. Although postoperative MRI showed complete removal of the macro PitNET, endocrinological testing indicated no improvement in GH or IGF-1 excess. Pathological examination of the surgical specimen revealed a gonadotropic PitNET. Therefore, we repeated the MRI scan and found a micro PitNET in the thin left normal pituitary gland. A second EES was successfully performed to remove the micro PitNET completely, and both endocrinological and pathological examinations confirmed that the disease was cured. Conclusion: Diagnosing acromegaly with low GH levels requires close monitoring. Double PitNETs are relatively rare and can cause incomplete remission of functional PitNETs.

Analysis of Insulinoma-Associated Protein 1 Expression in Pituitary Neuroendocrine Tumors.

Insulinoma-associated protein 1 (INSM1) is a representative diagnostic marker of neuroendocrine neoplasms (NENs); however, it has not yet been used to diagnose pituitary neuroendocrine tumors (PitNETs), according to the 2022 World Health Organization (WHO) classification of pituitary tumors. This study aimed to examine the expression of INSM1 using immunohistochemistry, in the various cell lineages of PitNET classified by hormone secretion and transcription factor expression. INSM1 expression in PitNETs (different subtypes) and normal pituitary tissues was immunohistochemically assessed. The results were interpreted as scores of 0 (negative), 1 (focally positive), or 2 (frankly positive), depending on the proportion of cell staining. Twenty-eight of 35 PitNET cases (80%) showed INSM1 positivity in their nuclei. The staining in each histological subtype of PitNETs was as follows: somatotroph tumors, score 0 = 3/5, score 1 = 1/5, score 2 = 1/5; lactotroph tumors, score 0 = 2/5, score 1 = 1/5, score 2 = 2/5; thyrotroph tumors, score 2 = 5/5; corticotroph tumors: score 1 = 1/9, score 2 = 8/9; gonadotroph tumors, score 0 = 2/10, score 1 = 0/10, score 2 = 8/10; and unclassifiable tumor, score 1 = 1/1. INSM1 expression in most PitNETs was obtained, similar to that in the normal pituitary gland; thus, INSM1 may maintain the characteristics of anterior pituitary cells and pituitary tumors.

Immunohistochemical Analyses of Mammalian Target of Rapamycin (mTOR) Expression in Pituitary Neuroendocrine Tumors (PitNETs): mTOR as a Therapeutic Target for Functional PitNETs.

Current therapeutic modalities for pituitary neuroendocrine tumors (PitNETs) include medication, surgery, and radiotherapy. Some patients have tumors that are refractory to current modalities. Therefore, novel treatment options are needed for patients with intractable diseases. Consequently, we examined the pathological data of PitNETs to study medical therapies. We retrospectively studied 120 patients with histologically diagnosed PitNETs. We used the data for the histopathological examination of hormones, such as growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone, thyroid stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and α-subunit, together with the immunohistochemical studies of the phospho-mammalian target of rapamycin (mTOR), cytokeratin (CAM5.2), somatostatin receptor (SSTR) type 2 and 5, Pit-1 (POU1F1/GHF-1), steroidogenic factor-1 (SF-1), and Tpit. GH-, PRL-, and SSTR5-immunopositive PitNETs had significantly higher percentage of mTOR-positivity, compared with GH-, PRL-, and SSTR5-immunonegative Pit NETs. Our results show that activation of the AKT/phosphatidylinositol-3-kinase pathway, including mTOR activation, might be related the development of PitNETs, especially GH- and PRL-producing PitNETs. Thus, mTOR is a potential target for treating functional PitNETs.

Cathepsin D Inhibits Angiogenesis in Pituitary Neuroendocrine Tumors.

Prolactin and growth hormone can acquire anti-angiogenic properties after undergoing proteolytic cleavage by Cathepsin D and bone morphogenetic protein 1 (BMP-1) into fragments known as vasoinhibins. Little is known about the effect of vasoinhibins on angiogenesis through the involvement of key cleavage enzymes Cathepsin D and BMP-1 in pituitary neuroendocrine tumors (PitNETs, formerly pituitary adenomas). The purpose of this study was to investigate the mechanism of action of Cathepsin D and BMP-1 on angiogenesis in PitNETs compared with that of pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor-2 (FGF2). A total of 43 patients were enrolled in a retrospective analysis and 22 samples were suitable for RNA extraction, including 16 nonfunctional PitNETs and six somatotroph tumors. The mRNA and protein levels of Cathepsin D, BMP-1, VEGF, and FGF2 were compared with those of von Willebrand factor, which was assessed to determine the vascularization of PitNETs. Cathepsin D and FGF2 were significantly correlated with vascularization in PitNETs. Both Cathepsin D and FGF2 are highly involved in angiogenesis in PitNETs, although the effect of Cathepsin D as an anti-angiogenic factor is dominant over that of FGF2 as a pro-angiogenic factor.

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.

Single-incision laparoscopic splenectomy for idiopathic thrombocytopenic purpura: report of a case.

We herein report a case of single-incision laparoscopic access (SILA) splenectomy for idiopathic thrombocytopenic purpura (ITP). A 24-year-old female patient with a diagnosis of ITP received corticosteroid therapy. However, as the side effects became serious, a splenectomy option was chosen. The SILA splenectomy using a transumbilical approach is cosmetically more attractive than a conventional laparoscopic approach, but it has an increased risk of major bleeding due to technical considerations. Therefore, we prioritized the patient's safety during the SILA splenectomy by choosing a left lower abdominal approach. The operating time was 123 min and blood loss was 1 ml. This was comparable to a conventional laparoscopic splenectomy. The present case appears to be the first SILA splenectomy reported in Japan. In our experience, a SILA splenectomy is feasible and safe, with favorable perioperative and shortterm patient outcomes. Further studies are necessary before the universal adoption of this new technique.

[A case of neuroendocrine carcinoma of esophagus with a remarkable response to chemo-radiotherapy].

A 69-year-old man visited our hospital with complaints of hoarseness and dysphagia. Computed tomography showed wall thickening in the middle thoracic esophagus, tracheal invasion, and para-aorta lymph node swelling. An esophagoscopy revealed an elevated lesion in the middle portion of the esophagus, which was pathologically diagnosed as neuroendocrine carcinoma, stage IV: T4N3M1. Two courses of concurrent chemoradiotherapy using cisplatin and etoposide were performed, followed by 4 courses of combined chemotherapy with carboplatin and etoposide. The patient showed clinical complete remission.