(The) effect of bromocriptine treatment for invasive prolactinoma

의학과/석사[한글] 기능성 뇌하수체 선종 중 가장 빈도가 높은 프로락틴 분비선종의 경우 다른 선종에 비하여 크기가 크고 침습성인 경우가 많다. 프로락틴 분비선종의 치료방법으로는 수술적 치료 외에 도파민 항진제인 bromocriptine이 쓰이고 있으나 macroprolactinoma나 giant prolactinoma의 경우에는 아직 논란의 여지가 남아있다. 특히 침습성 프로락틴 분비선종의 경우에는 빠른 종괴효과의 감소를 위해 bromocriptine 투여보다는 경접형골 접근법, 혹은 경두개 접근법을 이용한 수술이 시행되는 경우가 많다. 이 연구는 시야결손, 안구운동장애 등의 신경학적 이상이나 호르몬 이상증상을 주소로 내원한 20명의 침습성 프로락틴 분비선종 환자에게 일차적 치료로 bromociptine을 투여하여 수술적 치료 없이 충분한 신경학적, 내분비적 증상의 호전 및 종양크기의 감소의 효과를 볼 수 있는지에 대해 알아보고자 하였다. 연구대상은 본원에서 호르몬 검사와 자기공명영상(MRI, magnetic resonance image)을 이용하여 침습적 뇌하수체 선종을 진단 받은 20명의 환자를 대상으로 하였고, 이들 중 후에 수술적 치료를 시행했던 4명을 제외한 환자들에서 종양크기의 감소, 프로락틴치의 감소, 신경학적 증상의 호전, 호르몬 부족에 의한 증상이 회복되는 결과를 얻을 수 있었다. [영문]The prolactin secreting pituitary adenoma, prolactinoma, is the most common functioning pituitary tumor. Prolactinoma sometimes shows severe invasiveness to the adjacent cavernous sinus, especially in male. The dopamine agonist, bromocriptine, is used as a alternative treatment modality to surgery for prolactinoma, and its effectiveness in macroprolactinoma or giant prolactinoma also reported. But, in invasive prolactinoma, the transsphenoidal or transcranial approach for tumor removal has been more preferred treatment option for neurosurgeons. Especially, rapid decompression of mass effect and resolution of the neurologic deficit is demanded. We performed a prospective study of bromocriptine treatment as the first treatment option for the 20 invasive prolactinoma patients who presented with neurological or endocrinological abnormalities. As the result, 16 patient showed excellent result with only bromocriptine treatment. These patients showed not only marked reduction of tumor volume but also, improving clinical symptoms and other hormonal deficit. But, the remaining 4 patients required the surgical treatment due to no reduction of tumor size within 3 months. Probably these tumor had resistance to bromocriptine. So, even patients showed drop of prolactin level, it should require careful follow up of tumor size with MRI . We analyze the clinical outcomes, the changes on tumor size, and the serum prolactine and other hormone levels with bromcriptine treatment in invasive prolactinoma.ope

척수 신경교종 치료를 위한 테모졸로마이드(temozolomide)와 베바시쭈맵(bevacizumab) 병행치료의 효과

Dept. of Medicine/박사Study Design: The current standard therapies for the management of intramedullary malignant gliomas include surgery, chemotherapy, and radiotherapy. Concurrent or adjuvant temozolomide (TMZ) has been considered an emerging new treatment for intramedullary malignant gliomas. Although TMZ does not cure spinal cord tumor patients, it significantly improves patient survival and quality of life.Objective: In this study, we hypothesized that treatment with bevacizumab accelerates the therapeutic effect of TMZ on intramedullary gliomas in an animal model.Methods: C6 glioma cells were injected into the T5 level of the spinal cord, and TMZ and bevacizumab were administered 5 days after C6 inoculation. Tumor size was analyzed using histology and magnetic resonance imaging (MRI) at 13 days after tumor inoculation.Results: Histological analyses and MRI findings showed that combined treatment with TMZ and bevacizumab reduced tumor mass. Neurologic outcomes demonstrated that combined therapy improved hind limb function more than TMZ alone or control group.Conclusion: This study shows that bevacizumab could be useful in combination with TMZ to increase the therapeutic benefits of TMZ for intramedullary spinal cord tumors.ope

Major arterial aneurysms and pseudoaneurysms in Behçet's disease: results from a single centre

OBJECTIVE: Behçet's disease (BD) with arterial involvement is closely correlated with mortality and morbidity due to life-threatening complications such as arterial occlusion and aneurysm rupture. We aimed to determine the clinical characteristics of BD patients with aneurysms and pseudoaneurysms in the major arterial systems. METHODS: Medical records of 30 BD patients diagnosed with aneurysms or pseudoaneurysms in the major arterial systems were reviewed to determine the clinical characteristics of BD, the sites and types of arterial aneurysms or pseudoaneurysms, laboratory test results, and response to treatment. RESULTS: A total of 47 aneurysms and pseudoaneurysms (32 saccular aneurysms, eight fusiform aneurysms, and seven pseudoaneurysms) were detected in 30 patients. Most aneurysms and pseudoaneurysms (27 patients, 90%) had not ruptured. Symptomatic lesions presented in 21 patients (70%), and asymptomatic lesions were incidentally detected in nine (30%). Ten of the 30 patients (33.3%) presented two or more aneurysmal lesions. Recurrence was observed in five patients (16.7%) after treatment with stent graft (n = 3), graft interposition (n = 1), or graft embolization (n = 1). CONCLUSION: We suggest that BD patients diagnosed with major arterial aneurysms should be further evaluated to detect possible associated venous or arterial thrombosis formations or aneurysmal lesions at other sites.ope

Effect of Combined Bevacizumab and Temozolomide Treatment on Intramedullary Spinal Cord Tumor

STUDY DESIGN: C6 glioma cells and an intramedullary spinal cord tumor model were used to evaluate the effect of bevacizumab (Avastin) or temozolomide (TMZ). OBJECTIVE: In this study, we hypothesized that treatment with bevacizumab accelerates the therapeutic effect of TMZ on intramedullary gliomas in an animal model. SUMMARY OF BACKGROUND DATA: Recently therapies for the management of intramedullary malignant gliomas include surgery, chemotherapy, and radiotherapy. Concurrent or adjuvant TMZ has been considered an emerging new treatment for intramedullary malignant gliomas; however, high-dose application of TMZ has limitation of side effect. METHODS: C6 glioma cells were injected into the T5 level of the spinal cord, and TMZ and bevacizumab were administered 5 days after C6 inoculation (n = 7 for each group). Tumor size was analyzed using histology and magnetic resonance imaging at 13 days after tumor inoculation. RESULTS: Histological analyses and magnetic resonance imaging findings showed that combined treatment with TMZ and bevacizumab reduced tumor mass. The tumor volume of control group was 2.8-fold higher than combined therapy (P < 0.05). Neurological outcomes demonstrated that combined therapy improved hind limb function more than TMZ-alone group or control group (P < 0.05). CONCLUSION: This study shows that bevacizumab could be useful in combination with TMZ to increase the therapeutic benefits of TMZ for intramedullary spinal cord tumors. LEVEL OF EVIDENCE: N/A.ope

Clinical management and outcome of 36 invasive prolactinomas treated with dopamine agonist

Treatment of invasive prolactinoma, which has several characteristics including invasive growth into cavernous sinuses and formation of giant adenomas compressing adjacent neural structures, resulting in neurological dysfunction, has been very challenging. There are relatively few reports available describing long-term treatment outcome. Herein, we document the results of bromocriptine administration as initial treatment during average 44 months follow-up (up to 12 years) period. We retrospectively categorized 36 patients into four groups according to the results of 3 months of bromocriptine treatment: group 1, tumor volume reduction (TVR) >25% with normalized serum prolactin (NP) (n = 24); group 2, TVR >25% without NP (n = 4); group 3, TVR 50% with NP. Three patients (75%) in group 2 achieved TVR >50% with NP after treatment for 8 months. In group 3, four patients (80.0%) continued medication because of improvement of symptoms and achieved additional TVR (18.8-46.4%). Surgery was performed on five patients (one in group 2, one in group 3, and all three in group 4), and complete resection was achieved in four (80.0%). Overall, 25 (69.4%) of the 36 patients treated with bromocriptine had complete response and 6 (16.7%) had partial response but did not require surgery. Thus, the overall response rate was 86%, with only five patients (14%) requiring surgical debulking. NP was not achieved by surgery alone in all cases, even after total resection of tumor. Patients who achieve TVR >25% with NP with 3 months of bromocriptine administration had a high possibility of showing good long-term response (TVR >50% with NP) to bromocriptine. A higher dose of dopamine agonist (DA) or other DA should be considered for patients who achieve TVR >25% without NP.ope

Cervical spondylolysis: three cases and a review of the current literature

STUDY DESIGN: Case report. OBJECTIVES: To describe a rare case of cervical spondylolysis with an adjacent secondary dysplastic change, and to review the current literature regarding cervical spondylolysis. SUMMARY OF BACKGROUND DATA: Three patients presented with minor trauma history and radiographical C6 level spondylolysis. METHODS: Cervical spines were analyzed with plain radiography, multidetector computerized tomography, and magnetic resonance imaging. RESULTS: In all 3 patients, plain radiographs revealed a bilateral cleft of the C6 articular mass. The patients presented with long-term minimal discomfort of the posterior neck. In 2 patients, a trauma event increased the pain and produced neurologic deficits. In addition, an adjacent dysplastic change was present on imaging studying in 2 of the patients, 1 of whom also presented with a cord signal change above the spondylolytic level. CONCLUSION: Early diagnosis and appropriate management of cases of spondylolysis are important. In addition, surgical plans for cervical spondylolysis should be considered if the adjacent levels are unstable or fragileope

Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement

STUDY DESIGN: Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. OBJECTIVE: This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. SUMMARY OF BACKGROUND DATA: HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. METHODS: A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. RESULTS: Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. CONCLUSION: Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this studyope

Pediatric cervical chordoma: report of two cases and a review of the current literature

INTRODUCTION: The majority of chordomas occur between the fifth and seventh decades of life and are thus extremely rare in children, which account for less than 5% of all spinal chordoma cases. CASE REPORT: We report on the development of this rare condition in two boys aged 7 and 10 years. One patient presented with a palpable neck mass and dysphagia, while the other presented with posterior neck pain. Radiological studies revealed an extensive mass in the cervical vertebrae and paravertebral soft tissue of both patients. The tumors were subtotally removed in an attempt to improve the success of adjuvant proton beam radiotherapy. Pathological examination, which included immunohistochemical staining, revealed chordoma of the cervical spine in both patients. CONCLUSION: Although en bloc resection is the ideal modality for treatment of chordoma, such a procedure is often associated with a significant risk of surgical morbidity due to the tumor location. Therefore, piecemeal resection followed by postoperative adjuvant radiotherapy, including proton radiotherapy or radiosurgery, should be considered in such cases.ope

Robot-assisted anterior lumbar interbody fusion in a Swine model in vivo test of the da vinci surgical-assisted spinal surgery system.

STUDY DESIGN: the use of the da Vinci Surgical System to perform an anterior lumbar interbody fusion in a swine model to identify the technical properties, processes, merits, demerits, and limitations of a video-assisted robotic surgical system. OBJECTIVE: this study was designed to demonstrate the feasibility of using a robotic surgical system to perform spinal surgery. SUMMARY OF BACKGROUND DATA: video-assisted laparoscopic anterior fusion was first reported in 1995 and afterward was spotlighted for several years. However, this technique has not become popular because of technical difficulties and complications associated with video-assisted procedures on the spine. As such, there is a demand for investigations to improve this technology. The da Vinci Surgical System provides 3-dimensional visualization as well as uniquely dexterous instruments that are remarkably similar to human hands. Video-assisted surgery with the da Vinci Surgical System robot has already provided great value to the fields of urology, cardiology, gynecology, and general surgery over the last decade. Preclinical studies for application of this system in spinal surgery have recently been conducted. METHODS: a pig underwent anterior lumbar interbody fusion using da Vinci Surgical System assistance, with Tyche expandable cages used for preparation of endplates and cage placement. The setup time, operation time, amount of bleeding, and the number of complications associated with robotic manipulation were recorded. Before euthanasia, the animal underwent radiologic examination to confirm proper placement of cages. RESULTS: the total duration of the procedure took 6 hours, with some complications related to frozen armsand robotic arm collision. Even so, there was neither any significant nerve or vessel injury nor peritoneal organ damage. Furthermore, radiologic assessment confirmed proper position of the cage in the center of the disc space. CONCLUSION: use of the da Vinci Surgical System to perform an anterior spinal procedure was shown to be safe and effective in a swine animal model. The utilization of this advanced technology shows promise to reduce the incidence of complications compared with other approaches. It requires further testing in animal models and cadavers, along with serial comparisons to current procedures.ope

Robot-assisted anterior lumbar interbody fusion (ALIF) using retroperitoneal approach

BACKGROUND: Over the past few years, robot-assisted surgery has become increasingly popular, affecting virtually all surgical fields. It has been proven to overcome pitfalls of laparoscopic procedures, such as high complication rates and steep learning curve. We have, therefore, performed experimental anterior lumbar interbody fusion (ALIF) using retroperitoneal approach in swine model to test the feasibility of robot-assisted surgery in spinal surgery. METHOD: In this report, we describe the setup with the da Vinci surgical system, operative method, result and discuss technical aspects and the future of robot-assisted ALIF. FINDINGS: Experimental retroperitoneal dissection using robotic surgical system was successfully performed with great visual cue, minimal retraction and minimal bleeding. CONCLUSION: Although retroperitoneal approach for spinal fusion has never been attempted with robotic surgical system, we could demonstrate the possibility with swine model. Further studies and development of appropriate instruments will bring minimally invasive spine surgery to a new era.ope