Kentaro Horiguchi

Aggressive transsphenoidal resection of tumors invading the cavernous sinus in patients with acromegaly: predictive factors, strategies, and outcomes

OBJECT Cavernous sinus (CS) invasion is the most important preoperative predictor of remission in the surgical treatment of growth hormone-producing pituitary adenomas. The purpose of this study was to evaluate the effectiveness of an aggressive technique for removal of tumors invading the CS in patients with acromegaly. METHODS The authors retrospectively reviewed the cases of 150 consecutive patients with acromegaly who underwent primary transsphenoidal surgery in 2010 and 2011. The authors reviewed preoperative Knosp grade, intraoperative findings, histology of the medial wall of the CS, and surgical outcome according to the current consensus criteria for acromegaly. RESULTS Cavernous sinus invasion was identified in 55 patients (36.7%): definite CS involvement by the tumor was observed under direct vision in 41 patients (74.5%), while invasion was histologically verified in 39 patients (70.9%). Invasion increased in frequency with the higher Knosp grade but was observed in 14.4% (13 of 90) of Grade 0 and 1 tumors. Overall, the remission rate fulfilling stringent criteria was 84.7% (127 of 150). Although CS invasion was significantly associated with an unfavorable outcome (p < 0.0001), remission was achieved in 69.1% (38 of 55) of patients with invasion. No major complications occurred in this series. CONCLUSIONS Cavernous sinus invasion is the most significant, independent predictor of unfavorable outcome. Confirmation of invasion requires direct observation within the CS regardless of the microscope or endoscope used. Particularly in cases in which only the medial wall is involved, histological verification is always necessary to detect the occult invasion. Direct removal of the invading tumor, by sharp excision of the medial wall of the CS, is effective and safe and increases the chance of remission.

Acrolein, IL-6 and CRP as markers of silent brain infarction

We found previously that increased levels of polyamine oxidase (PAO) [acetylpolyamine oxidase (AcPAO) plus spermine oxidase (SMO)], and acrolein (CH(2)CHCHO) are good markers of stroke. We then investigated whether silent brain infarction (SBI) can be detected by measuring acrolein, PAO, or other biomarkers. Several biomarkers were measured in the plasma of 53 normal subjects and 44 subjects with SBI. It was found that the levels of protein-conjugated acrolein (PC-Acro), interleukin-6 (IL-6) and C-reactive protein (CRP) were significantly higher in SBI than in normal subjects. PAO was slightly higher in SBI than in normal subjects. Since the probability of SBI was increased with age, values were analyzed including age as a factor. When the combined measurements of PC-Acro, IL-6 and CRP were evaluated together with age using a receiver operating characteristic curve, SBI was indicated with 89% sensitivity and 91% specificity. The results indicate that measurement of PC-Acro together with IL-6 and CRP makes it possible to identify SBI with high sensitivity and specificity.

Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases

OBJECT The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. METHODS The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). RESULTS Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. CONCLUSIONS TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.

Endoscopic endonasal skull base reconstruction using a nasal septal flap: surgical results and comparison with previous reconstructions

The objective of this study is to evaluate the usefulness and reliability of endoscopic endonasal skull base reconstructions using a nasal septal flap. This study is designed as a retrospective review. Between April 2005 and November 2009, we performed 32 endoscopic endonasal skull base reconstructions for closure of large dural defects. Eleven patients underwent reconstructions using fat grafts or the fascia lata (non-flap group). Twenty one patients underwent reconstructions using a nasal septal flap with a balloon catheter (flap group). Incidence of postoperative cerebrospinal fluid (CSF) leaks and perioperative insertion rate of external lumbar drain (ELD) were compared between the two groups. Postoperative CSF leaks occurred in two patients (9.5%) in the flap group. Three patients (27.3%) presented CSF leaks in the non-flap group. The rate of insertion of ELD was 81.8% in the non-flap group. In the flap group, one patient (4.8%) should be placed with ELD postoperatively. The incidence of postoperative CSF leaks in the flap group was lower than in the non-flap group, whereas the rate of insertion of ELD in the non-flap group was higher than in the flap group. Endoscopic endonasal skull base reconstruction using a nasal septal flap without ELD seems to be useful and reliable for ventral skull base defects after endoscopic endonasal approaches as compared with our previous single-layer reconstructions using free fat grafts or fascia lata. The long-term effectiveness of nasal septal flaps to prevent intracranial complications should be confirmed.

Craniofacial Resection for Sinonasal Malignant Tumors: Statistical Analysis of Surgical Outcome over 17 Years at a Single Institution.

We present a retrospective analysis of surgical outcome of sinonasal malignant tumors. Overall survival (OS), disease-specific survival (DSS), local control (LC), and disease-free survival (DFS) were calculated in 32 patients. Prognostic factors for survival and functional outcomes were investigated. The median follow-up period was 70 months. At 5 years, OS, DSS, LC, and DFS rates were 0.722, 0.745, 0.851, and 0.707, respectively. Prognostic factors for poor OS were involvement of the frontal sinus (p = 0.023), T classification (T4, p = 0.025), surgical complications (p = 0.029), chemotherapy (p = 0.035) postsurgical infection (p = 0.043), involvement of the orbit (p = 0.048), histology (squamous cell carcinoma, p = 0.049), and radiotherapy (p = 0.043). Prognostic factors for poor DSS were radiotherapy (p = 0.030), chemotherapy (p = 0.036), positive surgical margin (p = 0.034), and T classification (T4, p = 0.050). LC was adversely influenced by surgical procedure (combined frontotemporal resection, p = 0.035) and positive surgical margin (p = 0.049). DFS was adversely influenced by positive surgical margin (p = 0.001). Prognostic factors for poor functional outcome were postsurgical infection (p = 0.039), postsurgical complications (p = 0.040), tumor location (maxillary sinus, p = 0.042, orbit, p = 0.0002), number of sinuses involved (number of sinuses involved was inversely proportional to functional outcome, p = 0.027), T classification (T4 p = 0.007), pathology (squamous cell carcinoma, p = 0.023), and chemotherapy (p = 0.048). Craniofacial resection was an effective surgical option.

Life-Threatening Intracranial Hypotension after Skull Base Surgery with Lumbar Drainage.

Although lumbar drainage (LD) is widely used in skull base surgery (SBS), no cases with intracranial hypotension (IH) following LD-assisted SBS have been reported, and skull base surgeons lack awareness of this potentially life-threatening condition. We report two cases of IH after LD-assisted SBS, a spheno-orbital meningioma and an osteosarcoma in the orbit. Despite a minimal amount of cerebrospinal fluid (CSF) drainage and early LD removal, severe postural headache and even a deteriorating consciousness level were observed in the early postoperative course. Neuroimages demonstrated epidural fluid collections, severe midline shift, and tonsillar sag compatible with IH. Epidural blood patch (EBP) immediately and completely reversed the clinical and radiologic findings in both patients. IH should be included in the differential diagnosis of postural headache after LD-assisted SBS that can be managed successfully with EBP. Persistent leakage of CSF at the LD-inserted site leads to IH. Broad dural dissection and wide removal of bony structure may be involved in the midline shift. EBP should be performed soon after conservative management fails. Further reports will determine the risk factors for IH development following LD-assisted SBS.

Short-term preoperative octreotide treatment for TSH-secreting pituitary adenoma.

Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p=0.09) and with and without tumor shrinkage (p=0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.

Multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells causing acromegaly associated with subclinical Cushing’s disease: a case report

BackgroundA functional pituitary adenoma can produce multiple anterior-pituitary hormones, such as growth hormone (GH) -producing adenomas (GHoma) with prolactin or thyrotropin stimulating hormone production in the same lineage. However, it is very rare that acromegaly shows subclinical Cushing’s disease (SCD) beyond the lineage. Here we describe the involvement of intratumoral coexistence with 2 types of hormone-producing cells associated with different lineage in acromegaly concomitant with SCD.Case presentationIn our study, we performed clinical evaluation of the patient showing acromegaly with SCD. To elucidate the mechanisms of this pathology, we analyzed immunohistochemistry and gene expression of anterior-pituitary hormones and transcriptional factors in the resected pituitary tumor. On immunohistochemical staining, most of the tumor cells were strongly stained for GH antibody, while some cells were strongly positive for adrenocorticotropic hormone (ACTH). Gene expression analysis of a transsphenoidal surgery sample of the pituitary gland revealed that ACTH-related genes, such as POMC, Tpit, and NeuroD1 mRNA, had higher expression in the tumor tissue than the nonfunctional adenoma but lower expression compared to an adenoma of typical Cushing’s disease. Further, double-labeling detection methods with a fluorescent stain for ACTH and GH demonstrated the coexistence of ACTH-positive cells (GH-negative) among the GH-positive cells in the tumor. Additionally, Pit-1 expression was reduced in the ACTH-positive cells from tumor tissue primary culture.ConclusionHere we described a case of a pituitary tumor diagnosed with acromegaly associated with SCD. We performed quantitative-expression analyses of transcriptional factors of the tumor tissue and immunohistochemistry analysis of tumor-derived primary culture cells, which suggested that the multihormonal pituitary adenoma concomitant with Pit-1 and Tpit lineage cells caused acromegaly associated with SCD.

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.

Prednisolone-responsive Postpartum IgG4-related Hypophysitis

We herein report the case of a 25-year-old woman who presented with severe headache and visual field defects after childbirth. Magnetic resonance imaging revealed marked swelling of the pituitary gland, and an endocrinological examination revealed panhypopituitarism and diabetes insipidus. An immunohistological analysis of a transsphenoidal biopsy sample of the pituitary gland showed the significant accumulation of an immunogloblin G4 (IgG4)-positive population, leading to the diagnosis of IgG4-related hypophysitis. The patient was treated with prednisolone, which markedly reduced the swelling of the pituitary gland, in association with recovery of the pituitary function. This is a rare case of biopsy-proven IgG4-related hypophysitis with a postpartum onset.