Efficacy and tolerability of gamma knife radiosurgery in acromegaly: a 10-year follow-up study

Objective  The long-term efficacy and safety of stereotactic radiosurgery by gamma knife (GK) still remain unknown. The aim of the study was to investigate the long-term efficacy and tolerability of GK in acromegalic patients.
Design and patients  Retrospective analysis for a median follow-up of 10 years. Thirty-five acromegalic patients from two referral centres in Milan submitted to GK (median margin dose: 20 Gy, median % isodose: 50) between 1995 and 2004.
Main outcome measures  GH/IGF-I secretion, anterior pituitary function, radiological imaging and ophthalmological data.
Results  Cure rate improved over time (up to 46% at 10 years), as did the proportion of patients achieving control on somatostatin analogues (from 12·5% at baseline to 50% at 10 years). Normal IGF-I values were observed in 82% of patients at their last visit. No visual impairment, disease recurrence, tumour growth or secondary cerebral tumour occurred. Half of the patients developed one or more new deficiencies, while two patients normalized their prior failures. In particular, new onset of clinical or subclinical hypoadrenalism occurred in 12/30 patients (40%), hypothyroidism in 3/28 (11%), hypogonadism in 2/15 (13%) and GH deficiency in 2/35 (6%). GH value at the time of GK was the best negative predictor of cure and margin dose was the best positive predictor of new hypopituitarism.
Conclusions  Over a 10-year period after GK radiosurgery, an increasing percentage of patients achieve cure, or adequate control of the disease on pharmacological therapy, at the expense of increasing novel pituitary deficiencies.     

伽玛刀治疗恶性梗阻性黄疸近期疗效观察

目的评价伽玛刀治疗恶性梗阻性黄疸的近期疗效。方法采用伽玛刀治疗恶性梗阻性黄疸患者20例。根据病变大小和部位选用不同大小的准直器,50%～70%等剂量曲线覆盖整个靶区,单次周边剂量给予3～5Gy,周边总剂量35～50Gy,分割8～12次,每周3～5次。结果血清胆红素从伽马刀治疗前的215.4±143.5μmol/L在治疗2周后降为98.4±54.5μmol/L(P0.05);CR3例,PR14例,总有效率(CR+PR)为85%;治疗前疼痛强度数字评估法(NRS)为6.96±1.21,治疗后为2.06±1.07(P0.01)。结论伽玛刀治疗恶性梗阻性黄疸安全有效,黄疸症状和疼痛明显缓解,提高了患者的生命质量。     

Role of gamma knife radiosurgery in the treatment of prolactinomas

Pituitary - Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of...     

Malignant transformation of a vestibular schwannoma after gamma knife radiosurgery

Stereotactic radiosurgery is used to treat benign tumours, but its long-term effects are not fully understood. Here we describe a vestibular schwannoma that underwent malignant transformation 6 years after gamma knife radiosurgery applied to the tumour remnant after a primary resection. Histological specimens of the original specimen did not show any atypical features. Genotyping showed a TP53 mutation in the recurrent tumour, which did not exist in the original tumour. Our results suggest that radiosurgery induced the malignant transformation, and we propose a cautious application of this treatment for benign tumours.     

Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion

We measured plasma insulin-like growth factor I/somatomedin-C (IGF-I/SmC) concentrations and mean 24-h GH secretion serially before and during therapy with the long-acting somatostatin analog SMS 201-995 in 21 patients with acromegaly. When mean plasma GH was elevated above 12.0 +/- 0.6 (+/- SE) micrograms/L, plasma IGF-I/SmC concentrations were uniformly high, but a decline of mean plasma GH below this value was accompanied by a linear decrease in IGF-I/SmC concentrations (r = 0.89; P less than 0.001). Even mildly abnormal mean GH concentrations (greater than 4.6 but less than 10 micrograms/L) were accompanied by high plasma IGF-I/SmC values. The log dose-response interrelation between mean 24-h plasma GH and IGF-I/SmC concentrations was linear (r = 0.86; P less than 0.001). We conclude that 1) an excellent log dose-response correlation between mean 24-h plasma GH and IGF-I/SmC concentrations is present in patients with acromegaly; 2) normalization of plasma IGF-I/SmC occurs only in patients with mean daily GH output within the normal range; and 3) determination of plasma IGF-I/SmC is an accurate indicator of normalcy of GH secretion and should be used in the diagnosis of active acromegaly as well as in monitoring the progress of therapy.     

Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis

Pituitary - Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary...     

Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.     

脑型血吸虫病误行伽玛刀治疗1例

脑型血吸虫病是一种异位血吸虫病，由于临床表现复杂，临床医务人员对其认识不足且缺乏警惕，易引起误诊误治。 1临床资料 患者57岁，男性，因头痛头晕6个月，加重1月入院。患者呈慢性痛苦病容，伴恶心、呕吐，步态不稳，语言障碍。入院后CT平扫示右侧小脑半球不规则低密度区阴影，呈“枫叶状”。考虑右小脑占位性病变，为进一步明确诊断行头部MRI检查。MRI采用signa 1．5T磁共振成像系统。使用头颅表面线圈，     

Use of the Leksell gamma knife in the treatment of prolactinoma patients

Objective  Pharmacological treatment with dopaminergic agonists (DA) is the treatment of choice for prolactinomas. Surgical and radiation treatment is also indicated in certain situations. We describe our 12-year experience in treating prolactinomas with the Leksell gamma knife (LGK).
Design  We followed 35 prolactinoma patients (25·7% microprolactinomas, 74·3% macroprolactinomas) treated with LGK irradiation. The mean follow-up period was 75·5 months. Prior to LGK irradiation, patients were treated with DA and 10 of them (28·6%) underwent neurosurgery. Indications for LGK irradiation were: DA intolerance (31·4%), DA resistance (45·7%) and efforts to reduce the DA dose or shorten the period of administration (22·9%). Pituitary function was monitored regularly at 6-month intervals. The central radiation dose range was 40–80 Gy (median 70 Gy), and the minimal peripheral dose was 20–49 Gy (median 34 Gy).
Results  Normoprolactinaemia was achieved in 37·1% of the patients who discontinued DA and in 42·9% of patients who continued DA treatment after LGK irradiation. The median time to prolactin normalization after discontinuation of DA was 96 months. No relapse was seen in any patient. After LGK irradiation, the prolactinoma stopped growing or decreased in size in all but one patient (97·1%).
Conclusion  LGK treatment resulted in normoprolactinaemia in 80·0% of the patients, all of whom had failed pharmacological treatment due to DA resistance or intolerance. After achieving normoprolactinaemia, no relapse of hyperprolactinaemia was observed in any patient. The size of the adenoma decreased even in those patients in whom it was not changed by previous DA treatment.     

Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly

BACKGROUND AND OBJECTIVE: The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy. PATIENTS AND METHODS: Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant. RESULTS: Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively). CONCLUSIONS: This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.     

Reduction of lung distensibility in acromegaly after suppression of growth hormone hypersecretion.

Whether the growth of the lungs in acromegaly is due to alveolar hypertrophy or alveolar hyperplasia is a subject of debate. To discriminate these hypotheses, we compared pulmonary distensibility and diffusing capacity among 11 patients with active acromegaly and 11 matched control subjects, evaluating the response of pulmonary distensibility and diffusing capacity to suppression of growth hormone (GH) hypersecretion. We performed lineal and exponential analyses of quasistatic pressure-volume curves. Patients with active acromegaly had a greater TLC, lung compliance, and shape constant, K, than did normal subjects. We found no significant differences between the study groups in carbon monoxide diffusing capacity or diffusing capacity per unit of alveolar volume. After treatment, patients with inactive acromegaly showed a reduced TLC (6.95 +/- 1.40 [mean +/- SD] L versus 6.35 +/- 1.23 L), reduced lung compliance (3.61 +/- 0.90 L/kPa versus 2.36 +/- 0.79 L/ kPa), reduced K coefficient (2.62 +/- 0.65 kPa(-)(1) versus 1.35 +/- 0.40 kPa(-)(1)), and increased maximal recoil pressure (1.74 +/- 0.38 kPa versus 2.28 +/- 0.25 kPa). We conclude that the increased lung distensibility with normal diffusion capacity demonstrated in patients with active acromegaly, which was partly reversible after suppression of GH hypersecretion, suggests that lung growth in acromegaly may result from an increase in alveolar size.     

伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析

目的：探讨伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效分析。方法将71例非小细胞肺癌脑转移瘤患者分为2组。观察组采用伽玛刀联合吉非替尼治疗,对照组采用全脑放射疗法联合吉非替尼治疗。对比2组患者的疗效、生存质量、生存率、不良反应。结果观察组和对照组总有效率(91.67% vs 82.86%)与控制率(97.22% vs 94.29%)比较差异均无统计学意义(χ2值分别为1.244、0.378,P 值均>0.05);观察组 Karofsky 得分有效率(72.22%)显著高于对照组(45.71%)(χ2=5.161,P<0.05);2组6个月、12个月的生存率比较差异均无统计学意义(χ2值分别为0.132、0.342,P值均>0.05);观察组脱发、头痛、肝功能损害的发生率显著低于对照组(χ2值分别为27.070、17.154、6.693,P值均<0.05)。结论伽玛刀联合吉非替尼治疗非小细胞肺癌脑转移瘤的疗效确切,能较好地控制肿瘤进展,提高生存率,且不良反应小,能有效改善患者生存质量。     

颅内动静脉畸形的伽玛刀治疗

颅内动静脉畸形(AVM)是常见的脑血管畸形。由于脑动脉与静脉间缺乏毛细血管，使动脉与静脉直接相通，形成短路，产生一系列病理及血流动力学改变，导致反复的颅内自发性出血、癫痫、进行性神经功能障碍等临床表现。AVM也是蛛网膜下腔出血最常见的原因之一。     

Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study

OBJECTIVE: Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi-centre acromegaly patient registry. DESIGN AND MEASUREMENTS: Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age. RESULTS: Information was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 +/- 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0.0003). GH levels were higher in patients with hypogonadism (P = 0.03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively. CONCLUSION: We developed a web-based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia.     

Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels

The pathogenesis of the goiter that is frequently found in patients with acromegaly is not known. Using ultrasonic scanning, we measured thyroid volume in 17 euthyroid patients with acromegaly and examined the relationships among thyroid size, plasma GH and insulin-like growth factor (IGF-I) levels, and serum thyroglobulin (TG) levels. The mean estimated thyroid volume in these 17 patients was 32.8 +/- 15.5 (+/- SD) mL, significantly larger than that in normal subjects (15.4 +/- 3.1 mL), and 64.7% of the patients had multinodular goiter, as identified by ultrasonography. Thyroid volume was positively correlated with plasma GH and IGF-I levels and heel-pad thickness, but not with the serum TSH level. In 7 patients, thyroid volume decreased in association with a decline in plasma GH and IGF-I levels after surgical treatment. The serum TG level was elevated in 7 of the 15 patients in whom it was measured, and the mean value was 51.7 +/- 62.7 (+/- SD) micrograms/L (normal, 12.6 +/- 6.4 micrograms/L). We found no correlations among the serum TG and TSH levels, plasma GH and IGF-I concentrations, and/or thyroid volume. However, serum TG decreased after surgical treatment, just as did plasma IGF-I. These observations together with the results of recent in vitro studies by others suggest that IGF-I is one of the factors involved in goiter formation, but the elevated serum TG levels in acromegaly are controlled not only by IGF-I but also by other factors.     

Assessment of the magnitude of growth hormone hypersecretion in active acromegaly: reliability of different sampling models

CONTEXT: The pulsatility of GH secretion in acromegaly poses difficulty in ascertaining true daily GH milieu in patients with this disease. Intensive GH sampling [every 10-20 (Q10-20) min for 24 h] is not practical in clinical practice. OBJECTIVE: Our objective was to ascertain reliability of abbreviated sampling protocols to reflect true 24-h mean GH concentrations in patients with acromegaly. DESIGN: An analysis of previously obtained plasma GH profiles was performed. SETTING: The analysis was performed at the General Clinical Research Center at the University of Michigan. PATIENTS: A total of 115 GH profiles obtained in 94 patients with active acromegaly were examined. INTERVENTION: Frequent blood sampling, i.e. Q10-20 min for 24 h, was performed. MAIN OUTCOME MEASURES: Concordance of 24-h mean GH concentrations derived from Q10- to 20-min samplings with abbreviated GH sampling schedules was performed. The study was planned after data collection. RESULTS: All abbreviated schedules of GH sampling correlated well with the true 24-h plasma GH means (i.e. Q10- to 20-min sampling) (R = 0.93-0.98; P < 0.0001 for all). In the GH range more than 20 microg/liter, only 5 and 9-h means had R values more than 0.9. Single GH concentrations less than 1 microg/liter had a positive predictive value of only 0.29, and those with less than 2.5 microg/liter had a positive predictive value of 0.67 vs. their corresponding 24-h mean GH values of the same magnitude. CONCLUSIONS: The intensity of GH sampling in patients with acromegaly may vary depending on the nature of the required information. Investigators and clinicians should be aware of the limitations of the abbreviated GH sampling protocols in acromegaly.     

立体定向放射联合肝动脉灌注化疗栓塞治疗原发性肝癌临床分析

目的探讨立体定向放射治疗联合经肝动脉化疗栓塞(TACE)治疗原发性肝癌的疗效。方法单纯TACE治疗58例,TACE联合伽玛刀治疗62例肝癌患者,比较治疗后的近期和远期疗效。结果在治疗后3个月,在单纯TACE治疗的58例患者中,总有效率(CR+PR)为60.3%(35/58),在TACE联合伽玛刀治疗组的62例患者中,总有效率(CR+PR)为79.0%(49/62,P0.01);TACE组治疗后1年、2年和3年生存率分别为67.2%(39/58)、34.5%(20/58)和18.9%(11/58),TACE联合伽玛刀组分别为72.6%(45/62)、41.9%(26/62)和22.6%(14/62)。结论立体定向放射治疗联合TACE治疗原发性肝癌是治疗肝癌安全有效的方法,可以提高患者的生存率。