Current management of prolactinomas

Prolactinomas constitute the largest group of pituitary adenomas in autopsy series. However, their relative incidence in recent surgical series is much less impressive since medical treatment with dopamine agonists is routinely employed, which in many cases leads to tumor shrinkage and normalization of prolactin levels. The clinical symptoms of hyperprolactinemia are menstrual dysfunction and galactorrhea in women and loss of libido and potency in men. Prolactinomas may present also as space occupying sellar mass lesions impinging on the adjacent structures like the pituitary gland, cavernous sinus and optic nerves. The standard primary treatment is medical by dopamine agonists. Prolactinomas are the prototype of tumors, the growth of which can be reliably and safely inhibited by specific drugs other than cytostatic chemotherapy. These unfortunately have side effects, like orthostatic hypotension, nausea and vomiting. The effects induced by dopamine agonists are suppressive but not tumoricidal. Thus, the therapeutic effect is only maintained as long as the drug is administered. Consequently, in most cases, treatment has to be continued life-long with a few exceptions, in whom normoprolactinemia persists even after discontinuation of dopamine agonists. Main indications of surgery in prolactinomas are intolerance of the medication, and tumors not responding to dopamine agonists. Occasionally, these may ultimately require radiation therapy. nobreak Remission rates in large series of surgically treated prolactinomas vary between 54% and 86%. In our consecutive series of 540 surgically treated prolactinomas, the normalization rate after transsphenoidal surgery basically depended on the preoperative prolactin levels, tumor size and extension. The remission rate of 82% in microprolactinomas with initial prolactin levels < 200ng/ml would even in small adenomas make one consider surgical treatment as an interesting alternative to long-term medical treatment.     

垂体泌乳素腺癌的诊断与治疗(附124例临床分析)

ObjectiveTo study the diagnostic and therapeutic features of prolactinoma.Methods124 patients with prolactinoma were studied in clinical manifestation,pathologic,endocrinological,radiographic and therapeutic features.ResultsThe average age of the male patients was 41.6 years,32.3 years of females.The major clinical manifestation in males were sexual and visual disfunction.In females,disfunction of menstruates and galactorrhea.Average serum prolactin was 1875.22 in males,376.6 ng/mL in females.Average diameter of the tumors was 38.05 mm in males,and 83.3% of the tumors were invasive,in females were 15.25 mm and 49%.After surgery,the average serum prolactin decreased to 385.84 ng/mL (P＜0.05),13 of 15 patients improved in sexual function,82.6% patients improved in eyesight and visual field.In females prolactin decreased to 23.93 ng/mL (P＜0.05),and 81 25% infertility with microprolactinoma got pregnancy,higher than controls of drugtherapy (P＜0.05).ConclusionIn males,the tumors were usually larger and more invasive,and serum prolactin levels were higher.The patients were elder.But in females,much younger than males,most of the tumors were microadenoma,and after operation the prolactin usually decrease to normal level and more chance of pregnancy.Results of a single therapy were with less satisfaction,we advocate integrated therapy around operation.     

The role of gamma knife radiosurgery in the management of pituitary adenomas

No treatment modality has been entirely successful in the management of pituitary adenomas. Although most patients with pituitary microadenomas can be cured by transsphenoidal surgery, the results are less satisfactory in macroadenomas in particular with suprasellar and/or parasellar extension. Additional treatment is then called for. Conventional fractional radiotherapy can often control tumour growth but is limited to 45–50Gy with a very slow reduction in elevated pituitary hormones and a high incidence of pituitary insufficiency. Stereotactic radiosurgery allows the delivery of radiation with high precision to the target with low doses to the surrounding tissues permitting higher radiation doses. Gamma knife radiosurgery using photon energy with gamma beams from multiple cobalt 60 radiation sources is now used in many centers. It can be carried out in an outpatient setting with one single treatment. A more rapid normalization of pituitary hormone hypersecretion than with conventional radiation can be achieved as well as arrest of tumour growth and reduction of tumour mass. We therefore consider gamma knife radiosurgery as a valuable compliment to pituitary surgery. Long-term prospective studies are needed to evaluate the frequency of pituitary insufficiency in patients where the target area is determined with stereotactic magnetic resonance imaging (MRI).     

Anesthetic management for supratentorial tumor surgery

Summary The principles of the perioperative anesthetic management of patients with supratentorial tumors are reviewed. Emphasis is placed upon intracranial pressure (ICP) dynamics and the multiple causes of intracranial hypertension which may occur during the perioperative period. The author describes his experiences using routine ICP monitoring in these cases, arguing that this may help both the neurosurgeon and the neuroanesthetist to avoid many of the pitfalls currently associated with the perioperative care of these patients.     

溴隐亭治疗女性垂体泌乳素瘤（附99例临床分析）

本文报道了溴隐亭治疗女性垂体泌乳素瘤９９例的疗效，其中单纯溴隐亭治疗６６例，手术加溴隐亭２９例，放疗＋溴隐亭４例，剂量５～７．５ｍｇ／ｄ，１４例加用克罗米酚，１例加用ｈＭＧ－ｈＣＧ。用药后８６．９％患者月经恢复，７１．２％恢复排卵，５８．４％妊娠。产后随诊２２例，１８例仍闭经伴溢乳。本文讨论了溴隐亭治疗女性垂体肿瘤的适应证剂量及辅助治疗。     

Late Development of Frontal Prolactinoma after Resection of Pituitary Tumor

The unusual case of a patient with a frontal lobe prolactinoma developed 14 years after resection of a histologically benign pituitary adenoma is presented. Sixteen years after resection of this frontal mass, and 30 years after the first intervention, the patient is symptom-free and without evidence of new intracranial tumors. The possibility that frontal tumor resulted as the late proliferation of microscopic tumor seeding that took place in the course of the first surgery, is suggested. Although this case can be considered as a pituitary carcinoma, the clinical course supports that tumor seeding from pituitary tumors not necessarily indicates a poor prognosis.     

Pituitary oncocytomas: clinical features,characteristics in cell culture,and treatment recommendations

To determine whether there are significant differences between oncocytomas and pituitary adenomas, we evaluated clinical features, treatment regimens and outcome in 23 males and 9 females (average age 64 years, range 43–81 years) with the histologic diagnosis of pure pituitary oncocytomas (>95% oncocytes). Symptom duration was six to twelve months in 6 cases (19%) and more than one year in 19 cases (59%). Three patients presented with sudden onset of symptoms, and were found to have hemorrhage within their tumors. Visual loss (69%) and symptoms of hypopituitarism (44%) were the most common presenting complaints. Preoperative endocrine profiles revealed abnormalities in most cases, including pituitary insufficiency in 56% and hyperprolactinemia in 59%. The tumors were typically large at presentation; all but one had suprasellar extension. 28 patients underwent transsphenoidal tumor resections; 4 underwent subfrontal craniotomies. Gross dural invasion was found at surgery in 11 cases. At a mean followup of 31 months (range 2–68 months), recurrent tumor was identified in 4 patients (12.5%). Tumor size, dural invasion, preoperative endocrine profile, and postoperative radiotherapy did not correlate with recurrence. Among seven oncocytomas grown in culture, five demonstrated two distinct cell types consisting of oncocytes and typical adenoma cells, respectively. Oncocytomas often have a different clinical presentation than functional pituitary adenomas.     

A case of prolactin-secreting pituitary carcinoma and its histological findings

Pituitary carcinomas are very rare. The diagnosis of pituitary carcinoma is defined by evidence of craniospinal and/or systemic metastasis, rather than by histological malignancies. We report a case of prolactin-secreting pituitary macroadenoma invading the cavernous sinuses at the time of initial treatment, which later metastasized to the cerebellum, medulla oblongata, and spinal axis. The patient survived approximately nine years following the initial diagnosis of a pituitary tumor and two years following the diagnosis of metastatic disease. Histological examination of the metastatic cerebellar tumor showed an adenoma with high cellularity and hyperchromasia, but no mitoses.     

颈动脉灌注卡铂治疗颅内恶性肿瘤17例报告

本文报告１７例颅内恶性肿瘤，经颈动脉灌注２０％甘露醇开放血脑屏障后注入卡铂治疗。并在化疗前及化疗后２０～４０天行ＣＴ检查比较瘤体变化。所追踪的１０例病人中，２例恶性脑膜瘤、２例星形细胞瘤Ⅱ～Ⅲ级病人已存活至今超过３年半。作者认为甘露醇开放血脑屏障后灌注卡铂，是安全、有效、副反应少的化疗方法。有利延长病人的生命。     

Incidence studies of primary and secondary intracranial tumors: A systematic review of their methodology and results

We reviewed the incidence studies of intracranial tumors to compare their methodology and identify whether there was evidence of true differences in incidence by time, place, age, or sex. Studies were identified from Medline (1966–95), bibliographies of relevant articles, and personal knowledge. For each study, various methodological details were recorded, along with the age-standardized incidence of all primary tumors and the crude and age/sex-specific incidences of different types of intracranial tumor. Methodological factors which significantly influenced the reported incidence were identified and the results of different studies were compared and combined in a meta-analysis if appropriate. Twenty studies (over 20,000 primary tumors) were included. Higher incidences of primary tumors were found in studies that: used many methods to identify cases (odds ratio [OR] 1.92); included a high percentage of asymptomatic patients (OR 2.03); did not require histologic confirmation of the diagnosis (OR 1.69). Studies from the 1980's reported higher incidences than in previous decades (OR 1.51), probably because of improved methodology. Comparable studies from the 1980's gave widely different incidence rates for all primary tumors (7.1–18.6 per 100,000 per year). In all studies, the incidence of neuroepithelial and meningeal tumors increased dramatically with age. Neuroepithelial tumors were 40% more common in men, whilst meningeal and cranial nerve tumors were about 80% and 40% more common in women, respectively. Further incidence studies are required to establish geographical and secular variations in the incidence of primary intracranial tumors but these must use comparable methodologies. Provisional guidelines for future studies are given.     

Clinical management of prolactinomas: A ten-year experience

A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mPab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP-and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.     

Intracranial tumors in adult population of the Varaždin County (Croatia) 1996–2004: a␣population-based retrospective incidence study

SummaryAim To estimate the incidence of intracranial tumors in the adult population of the Varaždin County, Croatia, for the 1996–2004 period.Methods Setting: Varaždin County General Hospital and four university hospitals in Zagreb, the capital of Croatia. Study period: January 1, 1996 to December 31, 2004. Incident patients: county residents admitted for newly diagnosed intracranial tumors according to the WHO diagnostic criteria. Demographic data were extracted from the 2001 Croatian census. Incidence rates (IRs) per 100,000 person-years (p-y) and annual IRs (per 100,000 persons) were determined and compared as incidence rate ratios (IRRs) with 95% CI.Results For primary intracranial tumors (PITs), IR was 12.1/100,000 p-y (95% CI: 10.3–14.2), comparable in men and women. The highest incidence was recorded for glioblastoma (IR 4.8, 3.7–6.2) and meningioma (IR 3.1, 2.2–4.2). The incidence of PIT was somewhat greater than that of metastatic tumors (IRR 1.58, 95% CI: 1.22–2.05, P<0.001). Metastatic tumors were more frequent in men than in women, especially metastatic lung tumors (IRR 6.08, 2.32–20.16, P<0.001). IRs of all PIT taken together, neuroepithelial tumors cumulatively, nonepithelial tumors cumulatively, glioblastoma and meningioma were higher in the population aged ≥40 vs. population aged ≤ 39 (all IRRs with 95% CI greater than 1, P<0.05 or < 0.001), comparable in men and women. Women were somewhat older than men at the time of diagnosis of PIT: median difference −6 years (95.1% CI: −10 to −1, P<0.05). Annual IRs for all these tumor categories showed increasing trends over the study period.Conclusion Overall, there was an increasing trend in the incidence of primary intracranial tumors in the Varaždin County. Data did not allow estimation for most of the specific tumor types.     

Endocrine inactive and gonadotroph adenomas: diagnosis and management

Endocrine inactive pituitary adenomas represent about one quarter of all pituitary tumors. By immunocytochemistry, most of these tumors are positive for intact gonadotropins and/or their subunits. Clinical presentation is usually secondary to mass effect symptoms, such as visual disturbances, headache, and hypopituitarism. Differential diagnosis is usually accomplished by neuroradiologic studies, even though in selected cases positron emission tomography and/or single photon emission tomography may aid to distinguish pituitary adenomas from other endocrine inactive lesions, such as meningiomas and craniopharyngiomas. Surgical management is usually considered the first choice treatment for patients with endocrine inactive pituitary adenomas because it is very effective in ameliorating symptoms of chiasmal compression and headache. Radical removal of the tumor, however, is difficult to obtain because of the frequent invasiveness into the cavernous sinus. Radiation therapy diminishes the likelihood of tumor recurrence, especially in patients with demonstrable tumor remnants after surgery. Medical therapy with dopaminergic drugs, somatostatin analogs, or gonadotropin-releasing hormone agonists or antagonists causes mild reduction of tumor size in few patients and, therefore, seems to be of limited value in the therapeutic management of patients with endocrine inactive pituitary adenomas.     

Intracranial osteosarcomas: Report of four cases and review of the literature

Four cases of intracranial osteosarcoma are reported. In three cases the tumors were primary neoplasms arising from the sellar region, base of the occiput and the parieto-occipital area. One case represented osteosarcoma metastatic to the cerebellum, a site not previously described, from a primary tumor at the femur. In addition, the current literature on intracranial osteosarcoma is reviewed.     

Endoscopic transsphenoidal surgery

Background: Endoscopic transsphenoidal surgery was developed under a minimally invasive surgical strategy. This endonasal transsphenoidal endoscopy eliminates a sublabial or transfixional incision, the use of a transsphenoidal retractor and any nasal packing. Materials and method: Reported are 160 patients who had undergone endoscopic transsphenoidal surgery from 1993 to 1999. Seventy were men and ninety women. Age ranged from 14 to 88 years (median 43 years). Among the 160 patients, 128 had pituitary adenomas, 9 had anterior fossa meningiomas, 7 had clival chordomas and 16 patients had other pathologies. Results: Among the 68 patients with hormone-none-secreting adenomas, 53 (78%) patients had gross total removal. Among the 35 patients with prolactinomas, 24 (71%) patients exhibited normalized prolactin levels postoperatively. Eleven (70%) patients among the 16 with Cushing's disease had normal postoperative cortisol levels. Among the 9 patients with acromegaly, 7 (78%) had normalized postoperative IGF-1 levels. Among the 9 patients with anterior cranial fossa meningiomas, 7 had gross total removal and 2 had subtotal removal. Among the 7 patients with clival chordomas, 5 had total removal and 2 had subtotal removal. One patient with a large calcified recurrent pituitary fibrosarcoma died postoperatively. Postoperative morbidities included cerebrospinal fluid (CSF) leak in 6%, meningitis in 1.2%, deterioration of anterior pituitary function in 11%, temporary diabetes insipidus in 4%, permanent diabetes insipidus in 3%, and sinusitis in 1.2%. Outpatient surgery was performed in 2 patients. One hundred and eleven patients (66%) stayed in the hospital only overnight. Postoperative discomfort was minimal. Conclusion: Endoscopic endonasal transsphenoidal surgery in this series resulted with comparable surgical outcomes to conventional microscopic transsphenoidal surgery. Patients' quick recovery, short hospital stays, and minimal postoperative discomfort have been observed.     

全脑 CT 灌注成像诊断邻近大血管颅内肿瘤

目的：探讨全脑 CT 灌注成像对颅内肿瘤病变的诊断作用,以期为临床颅内肿瘤病变的诊疗提供借鉴。方法：以我院2009年6月-2011年12月治疗的确诊为颅内肿瘤病变的患者为研究对象。先后对患者行全脑 CT 灌注成像扫描,获得并分析扫描图像中脑组织的多维全脑灌注图像、CT 血管成像,计算并分析全脑CT 灌注成像图像的病变实质部分和正常脑组织的达峰时间（TTP）、平均通过时间（MTT）、脑血流量（CBF）、脑血容量（CBV）参数、毛细血管表面通透性（PS）等灌注参数,通过灌注分析软件获得并分析时间-密度曲线（TDC）。结果：共纳入患者63例,在所有病例中,多维全脑灌注图像平均视觉评价分数明显高于单纯轴向灌注图（t =-11.852,P =0.000）,且对病变定位更为精确。CTA 图中63例患者中,有36例肿瘤发现供血大动脉,23例肿瘤有引流静脉,29例大动脉受压,15例大动脉被肿瘤包裹,17例静脉窦受压。统计分析示,全脑CT 灌注成像图像的病变实质部分和正常脑组织的 CBF、PS 等灌注参数之间差异具有统计学意义（P <0.05）。全脑 CT 灌注成像图像的病变实质部分和正常脑组织的 TTP、MTT、CBV 等灌注参数之间差异无统计学意义（P >0.05）。不同种类颅内肿瘤 TDC 比较,高级别胶质瘤速升速降,脑膜瘤与转移瘤速升缓降型。结论：全脑 CT 灌注成像图像不仅可以实现对邻近大血管颅内肿瘤的全面评价,有利于颅内肿瘤的术前整体评估和精确定位。对颅内肿瘤的诊断及评价肿瘤与周围大血管的关系、及颅内肿瘤病变的鉴别诊断具有一定的临床应用价值。     

Paraganglioma of the pituitary fossa: diagnosis and management

Paraganglioma of the sellar area is extremely rare with only six cases having been reported in the literature. Surgical removal of these tumors is difficult, and the transsphenoidal approach usually results in limited resection. Most authors who published reports on this tumor recommended radiation therapy after partial removal of the tumor. However, considering the benign nature of these tumors, the risk of radiation-induced endocrine insufficiency and optic neuropathy and the lack of proven effectiveness of radiotherapy, its value remains controversial.We describe a 48-year-old woman with parasellar paraganglioma who presented with headaches, visual loss and oligomenorrhea. Magnetic resonance imaging (MRI) showed an invasive tumor in the sellar and parasellar areas which extended to both cavernous sinuses and compressed the optic chiasm and the left internal carotid artery. Surgery by the transsphenoidal approach enabled only limited biopsy of the tumor. The patient was reoperated by an extended pterional approach which resulted in a subtotal removal of the tumor and adequate decompression of the adjacent structures. She received no adjuvant treatment during the 8-year postsurgical follow-up and remained in good health. A repeated MRI showed no change in the size of the residual tumor. Contrary to the therapeutic recommendations described in previous reports, we favor postoperative adjuvant therapy only if the symptoms or signs of cranial nerve compression persist following maximal tumor removal, or if there is evidence of subsequent growth of residual tumor.     

Diagnosis and treatment of carcinoid tumors

Carcinoid tumors belong to the family of neuroendocrine tumors, which are usually slow growing with distinct biological and clinical characteristics. The incidence of these tumors is approximately 2.5 in 100,000 people per year. The former classification system of foregut, midgut and hindgut tumors is still used in clinical routine, although there is a new World Health Organization classification. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. Proliferation capacity measured by Ki67 is used to guide forthcoming medical treatment. Localization procedures include computerized tomography, ultrasound, magnetic resonance imaging, somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemoembolization. Biological treatment includes cytotoxic agents, such as somatostatin analogs and interferon-α, which should be applied in slow-growing neoplasms. Combination regimens including cisplatin, etoposide, streptozotocin and 5-fluorouracil should be reserved for treatment of highly proliferating tumors. Future therapy of carcinoid tumors will be based on the specific tumor biology and treatment will be customized for each individual patient. New therapies, such as antiangiogenic agents and new, long-acting somatostatin analogs, together with further development of tumor-targeted treatments, will come into clinical use in the near future.