Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities.

PURPOSE: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. PATIENTS AND METHODS: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. RESULTS: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. CONCLUSION: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.     

Immunotherapy I: Cytokine gene transfer strategies

The cytokine approach to gene therapy of cancer stems from early studies of direct, repeated injection of recombinant cytokines at the tumor site, and extension of the bystander effect that enables a few cytokine gene transduced cells in a tumor to bring about its total destruction. This effect can be extended through the immune system, since cytokine-activated regression of a small mass of tumor cells can afford systemic protection. Transduced cells used as a vaccine provide a local concentration of both cytokine and tumor antigens. Cytokines sustain antigen uptake and presentation by increasing the immunogenic potential of the environment through the recruitment of antigen presenting cells and leukocytes, and activation of a cascade of events which amplify and tone up the efficacy of a vaccine. The promises and difficulties of this approach are discussed by considering what is still missing from experimental studies and what can best be done as soon as possible in animals and humans to reach compelling conclusions.     

Perioperative complications in acoustic neuroma (vestibular schwannoma) surgery.

OBJECTIVE: Retrospective study and review of the complications other than those related to the facial nerve and hearing, encountered in acoustic neuroma surgery. Also, an evaluation of hospital stay and its relation with various factors. STUDY DESIGN: Retrospective case review. SETTING: Tertiary neurotologic and skull base referral center. PATIENTS: A series of 707 patients who underwent surgical removal of acoustic neuroma from April 1987 to December 2001. INTERVENTIONS: The surgical approaches used were the enlarged translabyrinthine approach, the enlarged middle fossa approach, and the retrosigmoid approach. In a small number of cases, the operations were performed through other approaches. MAIN OUTCOME MEASURES: The duration of hospital stay and appearance of complications in the perioperative period along with their management. Results related to the facial nerve and hearing were not considered in this study. RESULTS: The most frequent complication was abdominal subcutaneous hematoma (site of fat harvest), which occurred in 23 patients (3.2%). Cerebrospinal fluid leak was present in 20 patients (2.8%), 15 of whom needed revision surgery. Other complications included VIth cranial nerve dysfunction in 12 cases (1.68%), subdural hematoma in 3 cases (0.4%), cerebellopontine angle hematoma in 4 cases (0.6%), cerebellar edema in 2 cases (0.28%), brainstem hematoma in 1 case (0.14%), transitory aphasia in 1 case (0.14%), and lower cranial nerve dysfunction in 1 case (0.14%). Mortality occurred in only one case (0.14%). Medical complications seldom occurred. The postoperative hospital stay ranged from 2 to 36 days, with an average of 6.4 days. The overall hospital stay diminished over time from 10.2 days in 1987 to 1990, to 4.9 days in 2001. There was a significant relation between hospital stay and tumor size, approach used, and presence/absence of complications. CONCLUSIONS: Perioperative complications in acoustic neuroma surgery do exist, but this study demonstrated how low the incidence is. The authors believe that the low percentage of complications is mainly attributable to the majority of operations being carried out in specialized clinics, where they are considered routine operations. They believe that following individualized approaches, depending on tumor size and on the preoperative function of the cranial nerves, is the proper way to reach a significant reduction in complications while maintaining a high percentage of total tumor removal. The results of this study, considered as a basis of comparison with other studies, will certainly be useful in preoperative patient counseling.     

Management of jugular paragangliomas: the Gruppo Otologico experience.

OBJECTIVE: The objective of this study was to review the outcome of surgical management in patients of jugular paragangliomas. STUDY DESIGN: We conducted a retrospective case review. SETTING: Tertiary care otology and skull base center. MATERIALS AND METHODS: Fifty-five patients with the diagnosis of a jugular paraganglioma (Fisch Class C and D Glomus Jugulare) were managed over a period of 15 years. All patients with adequate follow up and complete records (53 cases) were reviewed with emphasis on the results of surgical management and the factors influencing them. INTERVENTION: All 53 patients were managed with a view to surgically extirpate the tumor. The primary approach was the infratemporal fossa approach-Type A used in the majority of the patients. In eight cases, the procedure was staged owing to the presence of large intracranial extension. Three patients required additional procedures to ameliorate the after-effects of lower cranial nerve resection. RESULTS: Gross total tumor removal was achieved in 49 patients. There were five cases of recurrence. Coupled with the residual tumors in five patients, the surgical control achieved was 83%. There was no perioperative mortality. There were two cases of postoperative cerebrospinal fluid leak, both of which required surgical exploration and closure. The facial nerve was resected in seven patients. The overall preservation rate of clinically uninvolved lower cranial nerves was 75%. CONCLUSIONS: The low level of complications along with a high surgical control achieved makes surgery the primary mode of treatment in the vast majority of these tumors, regardless of the size and location.     

Management of the internal carotid artery in tumors of the lateral skull base: preoperative permanent balloon occlusion without reconstruction.

OBJECTIVE: To present our experience with permanent preoperative balloon occlusion of the internal carotid artery while dealing with different abnormalities of the lateral skull base and a comparison with the results mentioned in the literature. STUDY DESIGN: Retrospective case review. SETTING: Private neurotologic and skull base tertiary referral center. PATIENTS: Fifteen patients who underwent preoperative balloon occlusion of the internal carotid artery and surgery subsequently for various abnormalities of the lateral skull base between 1989 and 2002. INTERVENTIONS: Each patient was subjected to four-vessel angiography along with the manual cross-compression test and balloon test occlusion to assess the efficacy of the collateral circulation. After angiography, each patient underwent a preoperative balloon occlusion, after which a lateral skull base procedure was performed for removal of the abnormality. MAIN OUTCOME MEASURES: Only those patients showing evidence of adequate collateral cerebral circulation and a less than 1-second delay between the angiographic phases of the two cerebral hemispheres on angiography were considered fit for preoperative balloon occlusion. While under going the preoperative balloon occlusion, the patients were clinically assessed for the development of any neurologic symptoms and signs. Long-term follow-up after surgery was also based on the development of symptoms and signs of neurovascular compromise. RESULTS: A major complication in the form of long-lasting hemiplegia occurred in one patient (6.7%). This complication was the result of technical factors rather than an effect of cerebral ischemia, because it was caused by an intimal dissection produced by the catheter. A defect in the visual field occurred in one patient (6.7%) that resolved partially after antiplatelet therapy. There was no mortality in our series related to preoperative balloon occlusion of the internal carotid artery. CONCLUSION: Preoperative balloon occlusion of the internal carotid artery can still be considered a viable option for the management of the internal carotid artery during lateral skull base surgery. Proper preoperative evaluation of the adequacy and efficacy of the collateral cerebral circulation reduces the chances of postoperative neurovascular complications.