A multidisciplinary team approach to skull base chondrosarcomas.

OBJECT: The authors review their experience with treating skull base chondrosarcomas, which are much rarer than skull base chordomas and differ from them in prognosis and treatment. METHODS: Seventeen patients (12 male and five female patients) with histologically verified chondrosarcomas were followed up prospectively over a 12-year period. The mean age at presentation was 35.9 years. Most patients presented with cranial nerve palsies. Seven had undergone surgery prior to referral to the authors' unit. All underwent maximum surgical cytoreduction by the most direct surgical approach; only the two patients harboring the mesenchymal variant underwent radiotherapy. CONCLUSIONS: One patient died of a pulmonary embolus; the patients harboring mesenchymal chondrosarcomas died at 20 and 36 months, respectively, after treatment. Of the remaining patients, 93% were alive 5 years postsurgery and had a projected 10-year survival rate of 84% (mean survival time 9.3 years). These data emphasize the very slow progression of this tumor compared with skull base chordoma.     

颅底脊索瘤的长期随访研究

目的通过总结颅底脊索瘤手术后生存、复发等特点,探讨颅底脊索瘤的长期预后。方法采用电话、信件、门诊复查方式对1993年5月至2005年6月期间接受手术治疗的106例颅底脊索瘤患者进行随访,应用远期生活质量评分（Karnofsky Performance Sere,KPS）对全部患者术前、出院前、随访时的生存状况进行评分,SPSS生命表法计算生存率、复发率。结果79例得到随访,随访时间10-158个月,平均63．9个月,本组1、3、5、10年复发率分别为19．1％、34．7％、52．9％和88．3％,本组1、3、5、10年生存率分别为87．2％、79．4％、67．6％、59．5％。入院时KPS平均评分71．0分,出院前KPS平均评分72．5分,最后随访KPS平均评分67．1分,与出院前评分存在显著差异（P=0．020）。结论颅底脊索瘤预后不良,术后复发率呈逐年上升趋势,术后生存率前7年呈阶梯状下降,第8年后有逐渐平稳的趋势。手术治疗可以改善多数患者的远期生活质量。     

A multidisciplinary team approach to increasing AV fistula creation

Despite high patient comorbid factors, our Renal Care [table: see text] Group program was able to totally eliminate placement of AV grafts and to use only fistulae with an acceptable rate of catheter use--all within four years' time. This demonstrated the importance and value of a multidisciplinary vascular access team. Organization was the key element. All the team members were already in place prior to 1996, but they were not focused on vascular access and lacked education in this area. With the nephrologist not trained in fistula creation and not involved in that process, the absence of leadership led to a high number of dialysis grafts and catheters and frequent thrombotic and infectious complications. The nephrologist must assume the team leadership since he or she is the only provider who can interact with all other team members (see Table 3, p. 60). It is recommended that each nephrology group select a lead nephrologist to begin the team-building process (see Table 4, p. 60). A checklist (see Table 5) should be maintained for each pre-dialysis or dialysis patient as documentation for vein mapping and a surgical plan. This will make preoperative vein mapping mandatory for every patient. Education is important at all levels of the multidisciplinary team. This training effort should be started during nephrology fellowship, surgery and radiology residency, dialysis staff education programs, and renal networks. In 2002, the NW Renal Network led the way with fistula creation seminars, focusing on practicing nephrologists, surgeons, radiologists, and dialysis caregivers. The result of this Vascular Access Quality Improvement Program is pending.     

Gamma Knife surgery for skull base chordomas and chondrosarcomas

OBJECT: The purpose of this study was to evaluate radiosurgical outcomes in skull base chordomas and chondrosarcomas, and to determine which tumors are appropriate for stereotactic radiosurgery as adjuvant therapy following maximum tumor resection. METHODS: Thirty-seven patients (48 lesions) were treated using Gamma Knife surgery (GKS); 27 had chordomas, seven had chondrosarcomas, and three had radiologically diagnosed chordomas. The mean tumor volume was 20 ml, and the mean maximum and marginal doses were 28 and 14 Gy, respectively. The mean follow-up period was 97 months from diagnosis and 59 months from GKS. RESULTS: The actuarial 5- and 10-year survival rates after GKS were 80 and 53%, respectively. The actuarial 5- and 10-year local tumor control (LTC) rates after single or multiple GKS sessions were 76 and 67%, respectively. All patients with low-grade chondrosarcomas achieved good LTC. A tumor volume of less than 20 ml significantly affected the high rate of LTC (p = 0.0182). No patient had adverse radiation effects, other than one in whom facial numbness worsened despite successful tumor control. CONCLUSIONS: As an adjuvant treatment after resection, GKS is a reasonable option for selected patients harboring skull base chordomas or chondrosarcomas with a residual tumor volume of less than 20 ml. Dose planning with a generous treatment volume to avoid marginal treatment failure should be made at a marginal dose of at least 15 Gy to achieve long-term tumor control.     

Radiosurgery for chordomas and chondrosarcomas of the skull base

OBJECT: Chordomas and chondrosarcomas of the skull base are aggressive and locally destructive tumors with a high tendency for local progression despite treatment. The authors evaluated the effect of stereotactic radiosurgery (SRS) on local tumor control and survival. METHODS: Twenty-eight patients with histologically confirmed chordomas (18) or chondrosarcomas (10) underwent Gamma Knife SRS either as primary or adjuvant treatment. Their ages ranged from 17 to 72 years (median 44 years). The most common presenting symptom was diplopia (26 patients, 93%). In two patients, SRS was the sole treatment. Twenty-six patients underwent between one and five additional surgical procedures. Two underwent an initial transsphenoidal biopsy. The average tumor volume was 9.8 cm3. The median dose to the tumor margin was 16 Gy. RESULTS: No patient was lost to follow-up. Transient symptomatic adverse radiation effects developed in only one patient. The actuarial local tumor control for chondrosarcomas at 5 years was 80 +/- 10.1%. For chordomas both the actuarial tumor control and survival was 62.9 +/- 10.4%. CONCLUSIONS: Stereotactic radiosurgery is an important option for skull base chordomas and chondrosarcomas either as primary or adjunctive treatment. Multimodal management appears crucial to improve tumor control in most patients.     

Proton radiation therapy for chordomas and chondrosarcomas of the skull base.

OBJECT: Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated proton radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. METHODS: Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 ml or less remained locally controlled, compared with 56% of tumors larger than 25 ml (p = 0.02); 94% of patients without brainstem involvement did not experience recurrence; in patients with brainstem involvement (and dose reduction because of brainstem tolerance constraints) the authors achieved a tumor control rate of 53% (p = 0.04). Three patients died of their disease, and one died of intercurrent disease. Actuarial 5-year survival rates were 100% for patients with chondrosarcoma and 79% for patients with chordoma. Grade 3 and 4 late toxicities were observed in four patients (7%) and were symptomatic in three (5%). CONCLUSIONS: High-dose proton RT offers excellent chances of lasting tumor control and survival, with acceptable risks. In this series all small- and medium-sized tumors with no demonstrable brainstem involvement have been controlled; all such patients are alive. Surgical debulking enhanced delivery of full tumoricidal doses, but even patients with large tumors and disease abutting crucial normal structures benefited.     

Supraorbital-pterional approach to skull base lesions

A surgical approach to the skull base is described. It allows excellent exposure of the cranial base with minimal brain retraction. Deep lesions can be handled via subfrontal, transsylvian, or subtemporal routes during the same operation. This approach is most suitable for large lesions in the suprasellar, parasellar, and retrosellar areas and for those that extend into the cavernous sinus, along the tentorial notch, or into the orbit. After the single bone flap is replaced, there is little or no functional, anatomical, or cosmetic deficit. Our experience in 16 cases and suggestion for the use of this approach are presented.     

Endoscope-assisted far-lateral transcondylar approach to the skull base.

The far-lateral transcondylar approach was used in this cadaveric study in an attempt to evaluate the usefulness of endoscope-assisted microsurgery in this region of the skull base. The study was carried out using 4 latex-injected, formalin-fixed cadaver heads. After initial examination of intradural structures under an operating microscope, a zero degree 4 mm diameter solid-rod endoscope lens was introduced and guided into position under the direction of the operating microscope. Photographs of the regional anatomy were taken through this lens and through a 30 degree angled lens and compared to photographs of the anatomy taken through the microscope. Clear close-up views of the dural portals and intradural course of the cranial nerves were obtained using the endoscope. The endoscope was introduced through three corridors enclosed with cranial nerves, providing the surgeon with panoramic views of the vertebrobasilar arteries and anterior brainstem surface. The endoscope can be guided through narrow corridors and placed immediately adjacent to a region of interest at the skull base. It enables the surgeon to look around blind corners and work behind structures that are hidden from microscopic view.     

Current therapeutic options and novel molecular markers in skull base chordomas

Chordomas are extremely rare tumours. They arise in the spheno-occipital region in 35% of cases. Chordomas usually present benign histopathological features but often exhibit a malignant clinical behaviour. Radical surgical removal and high-dose radiation therapy seem to be effective in tumour control and to improve survival rate. Despite the advancements in microsurgical techniques and the development of radiation therapies, clival chordomas still represent a challenge. Nevertheless it appears that chordomas that have been resected to the same extent and that received post-operative radiotherapy might exhibit different rates of regrowth. This result supports the hypothesis that the recurrence rate of chordomas might be dependent on biological variables other than the extent of resection and the post-operative radiotherapy. Genetic and molecular studies on oncogenesis of chordomas are still limited, but they represent the basis for the development of molecular targeted therapies. We present a review of the current knowledge about skull base chordomas biology, therapeutic options and related clinical outcome.     

Proton radiation therapy for chordomas and chondrosarcomas of the skull base

Most patients with conventional radiotherapy after surgery die with local disease progression. The superior local tumor control and overall survival achieved with fractionated proton RT can be attributed to improved dose localization characteristics of protons, resulting in higher doses delivered. Patients with base of skull neoplasms are increasingly considered for stereotactic radiosurgery. Recently, Muthukumar et al reported for the University of Pittsburgh group on cobalt-60 Gamma Knife (Elekta Instruments, Atlanta, GA) therapy for 15 patients with chordomas or chondrosarcomas of the base of the skull. With tumor volumes ranging between 0.98 and 10.3 mL (mean, 4.6 mL), doses to the tumor margin varying from 12 to 20 Gy (median, 18 Gy) were delivered. Two patients were treated without histologic tumor confirmation. After a median follow-up time of 40 months, 2 patients had died of disease, 2 patients had succumbed to intercurrent disease, and 1 patient surviving at the time of analysis had developed tumor progression. Neither actuarial local control nor actuarial survival data were presented. In the LLUMC series, most tumors exceeded sizes reportedly suitable for radiosurgery or were of a highly irregular configuration. Nevertheless, in 11 patients, tumors less than 15 mL in size remained locally controlled as did tumors sized between 15 and 25 mL in 11 additional patients; these patients were thus potential candidates for stereotactic radiosurgery. At present, too few reports on radiosurgery contain sufficient patient numbers and statistical analyses to permit one to draw conclusions about the feasibility of radiosurgery for chordomas and chondrosarcomas of the base of the skull. A principal difference between proton RT and radiosurgery as currently practiced in most centers concerns target definition. In proton RT, the GTV is treated. In addition, a clinical volume is defined, which is distinctly different from the GTV in size and shape, to include the operative site and other areas of microscopic risk. In many instances, only the GTV is targeted in radiosurgery. Although it is certainly appropriate to explore the role that radiosurgical techniques may have in treating these tumors, results should be evaluated against the excellent outcome that can be achieved with fractionated proton RT, particularly in patients with tumors small enough and of favorable configuration and location to make them candidates for radiosurgery. The present problem of particle therapy is its limited availability. In the United States, only two proton centers can currently provide treatment for base of skull lesions. The HCL is soon to be replaced by a hospital-based facility at the MGH. Several other proton centers in the United States are currently under active consideration. Proton RT is an evolutionary process. Recent developments in proton RT include intensity modulated therapy and improvements in beam delivery systems, namely, the introduction of active beam scanning. These should further increase the degree of dose conformity. In addition, other heavy particles are also being investigated so as to combine the physical advantages of protons with the differential increased biologic effectiveness of particles in tumor as compared to normal tissues. A report from the Heavy Ion Research Facility in Darmstadt, Germany, has not revealed any increased acute toxicities in the first 13 patients with skull base chordomas or chondrosarcomas treated using carbon ions. Several important factors have emerged from recently published results: Patients with low-grade chondrosarcomas and male patients with chordomas have an excellent chance of durable tumor control and long-term survival after proton RT. Severe complications are within the acceptable range considering the high doses delivered and given the major morbidity associated with uncontrollable tumor growth in such patients. Female patients with chordomas experience increased early and late failures     

A posterolateral approach to the skull base: the petro-occipital transsigmoid approach

This posterolateral approach is directed to the petro-occipital skull base and is a combination of a suboccipital craniotomy, with an inferoposterior petrosectomy. The areas exposed are the jugular foramen, occipital condyle, lower clivus to the midline, petrous apex, tympanic cavity, the vertical portion of the intrapetrous carotid artery below the level of the eustachian tube, cerebellopontine angle, the jugulocarotid space in the upper neck. We evaluated 45 cases as follows: 13 chemodectomas, 14 lower cranial nerve schwannomas, 10 meningiomas, and 8 other lesions. The approach is indicated for extra-, intra-, and transdural lesions of the jugular foramen area. The transdural lesions could be extirpated in a single procedure without cerebrospinal fluid leak. This, in addition to preservation of the facial nerve, middle and inner ear functions, constituted the main advantages of this approach. Lower cranial nerve deficit formed the major morbidity in the present series and is still an unsolved problem in such cases.     

A multidisciplinary team approach to hydroxyurea-associated chronic wound with squamous cell carcinoma

Hydroxyurea (HU) has been shown to induce a variety of cutaneous adverse reactions, including severe leg ulcers. This report shows a successful treatment of a HU-induced chronic wound associated with squamous cell carcinomas (SCC). A 62-year-old patient affected with polycythemia vera and treated with HU for 10 years, presented with a non healing ulcer on a left heel. The patient gave a history of suffering from the wound for over 2 years. Biopsy showed evidence of invasive SCC. The patient underwent Mohs surgery and a greater saphenous vein ablation for polycythemia vera-associated vascular complications. The wound consistently decreased in size following successive debridements and coverage with human skin equivalent. The wound healed completely after a 6-month period. A multidisciplinary team approach to the treatment proved to be effective resulting in healing of this multifactorial chronic ulcer.     

Establishing tumor cell lines from aggressive telomerase-positive chordomas of the skull base. Technical note

Permanent cell cultures are invaluable tools for understanding the biological characteristics of tumors. In the present study the authors report on the establishment of permanent human cell lines from three cases of aggressive chordomas of the clival region. All of the parental tumors showed telomerase activity. Cultured chordoma cells had a doubling time of 5 to 7 days and grew as a monolayer of cells that retained both the immunophenotype and the p53 status of the parental tumor. In vitro, chordoma cells overexpressed telomerase, supporting the hypothesis that this enzyme is required for the immortalization process.     

Effectiveness of a multidisciplinary team approach to hip fracture management

The purpose of the current study was to evaluate the effectiveness of a multidisciplinary Hip Fracture Service in the treatment of hip fractures in elderly patients. Baseline information and hospital outcomes were compared for 510 patients over the age of 65 with hip fracture treated before and after the institution of the Hip Fracture Service. Data included basic demographic data, admission laboratory results, surgical information, number of comorbidities, mortality, medical complications, discharge information, time to surgery, and length of stay in hospital. The demographics of the two groups of patients were similar. Patients treated as part of the Hip Fracture Service had fewer medical complications (36% vs. 51%), more often had surgery within 24 hours (63% vs. 35%), and had shorter hospital stays (mean, 5.7 days vs. 8.1 days) than patients treated before the Hip Fracture Service. These findings provide the rationale for a prospective, randomized trial of the service.     

Operative approach to the frontal skull base: extensive transbasal approach

An operative technique called the extensive transbasal approach is reported with the operative results of 11 cases. This is an operative mode in which en bloc osteotomy of the orbital roofs and frontal sinus is performed after ordinary bifrontal craniotomy. Through this approach, a far wider operative space than that afforded by conventional operative techniques is possible, and reconstruction of the frontal base can be made securely. We consider this approach of major clinical value.