Stereotactic radiosurgery for brain metastasis from renal cell carcinoma

The PRESAGE database is a collaborative resource for structural genomics. It provides a database of proteins to which researchers add annotations indicating current experimental status, structural predictions and suggestions. The database is intended to enhance communication among structural genomics researchers and aid dissemination of their results. The PRESAGE database may be accessed at http://presage.stanford.edu/     

Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

INTRODUCTION: Improvements of the results of combined chemoradiotherapy (CRT) in esophageal cancer has led several groups to adopt a non surgical attitude specially in case of complete response (endoscopy +/- biopsy). Few information are available about the follow-up of these patients. We studied long-term results of 35 patients who underwent resection after complete response to preoperative chemoradiotherapy. PATIENTS AND METHODS: 161 patients with resecable carcinoma of the thoracic esophagus have received the same protocol of CRT (cisplatin 80 mg/m2, radiation therapy split course: 37.5 Gy) all patients were followed every for 4 months (no lost of view). RESULTS: Complete response (endoscopy and biopsy) was obtained for 35 patients (21.7%), 19 of them (54%) had pathologic complete response (PCR) (no tumor in the specimen), 16 have microscopic foci of residual tumor (46%). The overall 5-year survival rate was 49.8% for the whole group (median survival 64 months), 70% for the group without tumor in the specimen, 48% for the group with microscopic foci of residual tumor (NS). CONCLUSIONS: One half of the complete response (endoscopy + biopsy) have not a pathologic complete response (microscopic foci of residual tumor in the specimen). The 49.8% of five year survival suggests a benefit from esophagectomy for complete response after combined chemoradiotherapy.     

First-line treatment of advanced nonsmall cell lung carcinoma with docetaxel and vinorelbine

BACKGROUND: Docetaxel and vinorelbine are active agents in the treatment of nonsmall cell lung carcinoma (NSCLC). The efficacy and toxicity of this combination was evaluated in a Phase II study in patients with advanced NSCLC. METHODS: Forty-six chemotherapy-naive patients (44 men and 2 women with a median age of 64 years) with NSCLC (11 with Stage IIIB and 35 with Stage IV disease) were entered into the study; the World Health Organization (WHO) performance status was 0, 1, and 2 in 32, 11, and 3 patients, respectively. Patients received vinorelbine (25 mg/m2) on Day 1 and docetaxel (100 mg/m2) on Day 2 in cycles repeated every 3 weeks. Granulocyte-colony stimulating factor was given to all patients from Day 3 to Day 10. RESULTS: One hundred and seventy-seven courses of chemotherapy were administered. Adverse events included WHO Grade 4 neutropenia (15 patients), Grade 3/4 thrombocytopenia (3 patients), Grade 3 anemia (2 patients), Grade 2 and 3 neurotoxicity (7 patients and 1 patient, respectively), and Grade 3 fatigue (2 patients). Twenty patients (43%) required hospitalization: 11 (24%) for neutropenic fever (2 deaths from sepsis), and 9 (20%) for nonneutropenic pulmonary infections (2 deaths from cardiopulmonary insufficiency). The median overall survival was 5 months and the 1-year survival was 24%. Four complete responses (9.8%) and 11 partial responses (26.8%) (overall response rate of 36.6%; 95% confidence interval, 21.8-51.3%) were documented in 41 evaluable patients (intent-to-treat: 32.6%). Stable and progressive disease occurred in 13 patients each (31.7%). The median duration of response was 5 months and the median time to progression was 3 months (6 months for the responders). CONCLUSIONS: This schedule of docetaxel and vinorelbine combination is effective but its relatively high incidence of complicated neutropenia precludes its general use in patients with advanced NSCLC.     

Large cell carcinoma of the lung metastatic to nuchal muscle

An attempt to achieve problem-based examining by the structured assessment of presentations is described. Students can choose to participate in the scheme in teams and then elect to use their awarded mark instead of part of the formal examination assessment. The element of choice of the study or examination method is seen as being a valuable element of the scheme. The scheme can be introduced without radical revision of existing curricula or substantial investment of staff time, and meets some of the expressed desires of the UK General Medical Council in terms of the introduction of novel methods of assessment.     

Stereotactic radiosurgery with linear accelerator

Stereotactic radiosurgery is a method that applies a radiation dose to a limited and well-defined volume while the irradiation of adjacent healthy tissues is minimized. It is most commonly used in the treatment of intracranial lesions because the skull hardness assures the stable location of its contents. Treatment of the rest of the body has recently been proposed and carried out, using original immobilization systems. Stereotactic radiosurgery was first described in 1951 by the Swedish neurosurgeon Lars Leksell who originally used X-rays and then high-energy protons as a source of radiation. In the '80s photons from linear accelerators were used as radiation source, with various stereotactic systems and computerized treatment planning. The method used with all radiosurgical systems, regardless of the source of irradiation, is similar. The lesion is detected with common diagnostic imaging and adequate location frames. At present, to prevent errors in location, MRI and CT data are matched using an Image Fusion computer program. The objective of stereotactic radiosurgery is to destroy tumor cells or to induce changes in tissues that, as in brain arteriovenous malformations lead to the occlusion of their abnormal vessels. Stereotactic radiosurgery is increasingly used today in the treatment of a variety of intracranial lesions to the patients' benefit.     

Stereotactic radiosurgery for intracranial malignancies

Stereotactic radiosurgery has historically been used for arteriovenous malformations and benign tumors but has rather recently been used as a tool in the multimodality management of intracranial malignancies. Radiosurgery has been shown to be highly effective in the management of small metastatic brain tumors and has proven effective in controlling small brain metastases that progress after prior fractionated radiotherapy. The technique is also a reasonable, low morbidity alternative to surgical resection in the initial management of patients with solitary brain metastasis. In selected patients with small, relatively spherical, high-grade gliomas, radiosurgery appears to produce tumor control, survival, and toxicity similar to that of brachytherapy. However, compared with brachytherapy, radiosurgery has the advantage of lower initial morbidity, reduced hospital stay, reduced radiation exposure to personnel, and lower costs. Future clinical trials should further define dose-response relationships and the optimum role for radiosurgery in the management of malignant intracranial neoplasms.     

Stereotactic radiosurgery for tentorial meningiomas

Radical microsurgical resection is the procedure of choice for tentorial meningiomas. Despite advances in microsurgery, tentorial meningiomas continue to challenge surgeons and patients. To evaluate the response of tentorial meningiomas, we evaluated 41 patients who had Gamma knife stereotactic radiosurgery during a 9 year period. Patient age varied from 32 to 79 years. Headache, trigeminal neuralgia, or facial paraesthesia were the most common presenting symptoms. Sensory deficits in the distribution of the trigeminal nerve were the most common finding. Eighteen patients (44%) had undergone between 1 and 5 (mean, 1.9) resections prior to radiosurgery; 23 had tumors diagnosed by neuroimaging. The average tumor diameter in this series was 20 mm. The maximum tumor dose varied from 24 to 40 Gy (mean, 30.5 Gy), and the tumor margin dose varied from 12 to 20 Gy (mean, 15.3 Gy). During the average follow-up interval of 3 years (range, 1-8 years), 19 patients had clinical improvement, 20 remained stable, and 2 patients deteriorated. Follow-up imaging showed a reduction in tumor size in 18 patients, no further tumor growth in 22, and an increase in tumor size in one (overall tumor control rate of 98%). Stereotactic radiosurgery using the Gamma Knife was a safe and effective primary or adjuvant treatment for patients with tentorial meningiomas.     

Stereotactic radiosurgery for recurrent malignant gliomas

PURPOSE: To evaluate the role of stereotactic radiosurgery in the management of recurrent malignant gliomas. PATIENTS AND METHODS: We treated 35 patients with large (median treatment volume, 28 cm3) recurrent tumors that had failed to respond to conventional treatment. Twenty-six patients (74%) had glioblastomas multiforme (GBM) and nine (26%) had anaplastic astrocytomas (AA). RESULTS: The mean time from diagnosis to radiosurgery was 10 months (range, 1 to 36), from radiosurgery to death, 8.0 months (range, 1 to 23). Twenty-one GBM (81%) and six AA (67%) patients have died. The actuarial survival time for all patients was 21 months from diagnosis and 8 months from radiosurgery. Twenty-two of 26 patients (85%) died of local or marginal failure, three (12%) of noncontiguous failure, and one (4%) of CSF dissemination. Age (P = .0405) was associated with improved survival on multivariate analysis, and age (P = .0110) and Karnofsky performance status (KPS) (P = .0285) on univariate analysis. Histology, treatment volume, and treatment dose were not significant variables by univariate analysis. Seven patients required surgical resection for increasing mass effect a mean of 4.0 months after radiosurgery, for an actuarial reoperation rate of 31%. Surgery did not significantly influence survival. At surgery, four patients had recurrent tumor, two had radiation necrosis, and one had both tumor and necrosis. The actuarial necrosis rate was 14% and the pathologic findings could have been predicted by the integrated logistic formula for developing symptomatic brain injury. CONCLUSION: Stereotactic radiosurgery appears to prolong survival for recurrent malignant gliomas and has a lower reoperative rate for symptomatic necrosis than does brachytherapy. Patterns of failure are similar for both of these techniques.     

Surgical analysis for metastatic lung tumor from renal cell carcinoma

Metastatic lung tumor from renal cell carcinoma were studied in 29 cases. Eighteen patients were treated surgically, 11 were treated non-surgically. The overall 5-year survival rate with the patients of pulmonary resection was 53.5%, and that with those of conservative therapy was 0%, and this difference is statistically significant (p < 0.05). There was no significant difference in any characteristics such as sex, age, stage, grade, disease free interval, metastatic pattern and combination with or without interferon therapy. There was no significant difference in surgically treated patients with pulmonary metastasis in terms of any factors such as age, sex, stage, grade, disease free interval, pulmonary metastasis pattern, metastatic number, surgical procedure, combination with or without interferon therapy statistically. Analysis for the surgically treated patients with pulmonary metastasis from renal cell carcinoma shows no significant difference in prognosis with any characteristics. This result shows efficacy of surgery even if for the patients with synchronous bilateral multiple pulmonary metastasis from renal cell carcinoma.     

Energy balance in nonsmall cell lung carcinoma patients before and after surgical resection of their tumors

BACKGROUND: The purpose of this study was to investigate whether surgical removal of a tumor influences energy balance, body weight, and body composition in lung carcinoma patients. METHODS: In 53 nonsmall cell lung carcinoma (NSCLC) patients, resting energy expenditure (REE, measured by ventilated hood), energy intake (EI, determined by diet history), body weight, and body composition (fat free mass [FFM], measured by bioelectrical impedance analysis) were all determined before tumor resection. In 39 of 53 patients, REE, EI, body weight, and body composition were also measured 3, 6, and 12 months after tumor resection. RESULTS: Thirty-six of 53 patients (68%) were found to be hypermetabolic. Fourteen patients were excluded from the repeated measurements. Patients with curative tumor resection (n = 30) showed an increase in body weight over a 1-year period, in contrast to patients with tumor recurrence (n = 9), who lost weight (+3.5 vs. -3.6 kg, P < 0.005). The weight gain was caused predominantly by an increase in fat mass (FM), while the weight loss was caused for more than half by a decrease in FFM. Body weight was increased in hypermetabolic patients (n = 20) as well as patients with normal metabolism (n = 10) 1 year after successful removal of their tumors. However, although EI/REE was significantly increased in hypermetabolic patients (from 106% to 140%, P < 0.05), it was not changed in patients with normal metabolism. CONCLUSIONS: Hypermetabolic NSCLC patients undergoing curative resection show an improvement in energy balance caused by both a decrease in REE and an increase in EI. This positive energy balance results in weight gain, which is caused predominantly by an increase in FM.     

Massive lower gastrointestinal haemorrhage secondary to metastatic squamous cell carcinoma of the lung

Clinically significant symptoms due to gastrointestinal metastases from primary lung cancers is rare. A case of life-threatening lower gastrointestinal haemorrhage secondary to metastatic squamous cell carcinoma of the lung is reported. Previous reports of such metastases are reviewed, with reference to management and prognosis. After resection of colonic metastases from squamous cell lung cancer, survival is similar to that for primary disease. It is suggested that patients with known or suspected squamous cell lung cancer presenting with lower gastrointestinal symptoms be managed as aggressively as those with no previous history of disease.     

Gestational choriocarcinoma metastatic to the brain treated successfully by stereotactic radiosurgery and chemotherapy

This report analyzes the intracorporal lengths of 236 consecutive organically impotent men who underwent insertion of a penile prosthesis. The average right or left intracorporal length in this series was 20.9 cm, with a standard deviation of 2.2 cm. Intracorporal length ranged from 14-27 cm. This data may be used as reference ranges for penile prosthesis manufacturers, and for Urologists who implant prostheses or perform penile lengthening procedures.     

Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma

BACKGROUND: Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. METHODS: Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. RESULTS: Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. CONCLUSIONS: Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.     

Nephrectomy before interleukin-2 therapy for patients with metastatic renal cell carcinoma

PURPOSE: The management of metastatic renal cell carcinoma remains challenging and controversial. There is some evidence of improved response to interleukin-2 (IL-2) based immunotherapy in patients who undergo nephrectomy before systemic treatment. However, recent reports have suggested that surgery prior to immunotherapy may not be an efficient strategy, since many patients will not be able to receive systemic treatment after nephrectomy. We describe our criteria for determining which patients are candidates for nephrectomy before immunotherapy and present our series of patients treated with this approach. MATERIALS AND METHODS: Based on our initial experience with IL-2 based immunotherapy we developed certain inclusion criteria for treatment with initial nephrectomy followed by systemic immunotherapy, including greater than 75% debulking of tumor burden possible, no central nervous system, bone or liver metastases, adequate pulmonary and cardiac function, and Eastern Cooperative Oncology Group performance status of 0 or 1. In addition, patients in whom biopsies show other than predominantly clear cell type histology are excluded. From 1991 through 1996, 28 patients met these criteria and were treated with this approach. Patients were followed to determine the number receiving immunotherapy as well as overall response and survival rates. RESULTS: Radical nephrectomy was performed in all patients. One patient died of respiratory failure from disease progression 1 month after nephrectomy. Another patient had poor pulmonary function and, therefore, was treated with an alternative cytokine therapy. The remaining 26 patients (93%) received at least 1 course of IL-2. Median interval between nephrectomy and initiation of immunotherapy was 1.5 months (range 1 to 3). Overall response rate was 39% with 5 complete (18%) and 6 partial (21%) responses. Actuarial median survival of the entire group was 20.5 months (range 1 to 66) from the initiation of treatment. Currently 13 patients are alive, including 8 who are disease and/or progression-free. CONCLUSIONS: Using these strict criteria nephrectomy can be effectively performed before immunotherapy without compromising the likelihood that patients will receive systemic treatment. The activity of IL-2 in patients treated with this approach is encouraging and justifies its consideration in properly selected patients.     

Small bowel perforation secondary to metastatic lung carcinoma

Since 1961, there have been a total of seven patients with small bowel perforation caused by metastatic lung carcinoma reported in the literature. Perforation of the small bowel to metastatic lung carcinoma must be considered when evaluating older patients who have histories of heavy cigarette smoking and signs and symptoms suggestive of pulmonary neoplasia. Primary resection and end-to-end anastomosis of the perforated bowel is the treatment of choice. No patient with small bowel perforation secondary to lung carcinoma has survived more than four months.     

Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q

Loss of heterozygosity on chromosome 11q23 is observed at high frequency in human nonsmall cell lung carcinomas (NSCLCs), suggesting the presence of a tumor suppressor gene. Previous analysis of DNA from 79 patients identified a commonly deleted segment of 5 centimorgans. Complementation analysis was used to further localize a putative tumor suppressor gene. Three yeast artificial chromosome (YAC) clones spanning the minimal loss of heterozygosity region were modified, and spheroplast fusion was used to transfer them into human A549 NSCLC or murine Lewis lung carcinoma (LLC) cell lines. The resulting yeast x human hybrid cell lines containing an intact copy of a 1.6-Mb YAC, 939b12, showed reduced growth in vitro. Injection of parental A549 cells into athymic (nu/nu) mice resulted in tumor formation at 27 of 28 injection sites. In contrast, two independent 939b12-containing cell lines formed tumors at only 3 of 20 injection sites. 939b12 also suppressed tumor formation by LLC NSCLC cells in nude mice, but YACs 785e12 and 911f2, which flank 939b12, had no suppressor activity. Further localization of tumor suppression activity on 939b12 was accomplished by introduction of defined fragmentation derivatives into A549 cells and by analysis of YACs that were broken on transfer into LLC cells. This complementation approach localized tumor suppression activity to the central 700 kb of 939b12 and provides a functional assay for positional cloning of this tumor suppressor gene.