局部热疗联合腔内化疗对恶性胸腔积液的疗效观察

Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group,breast cancers and lung cancers were 80.8% vs 54% (P ＜ 0.01), 86.7% vs 56.3% (P ＞ 0.05) and 78.4% vs 52.9% (P ＜ 0.05)respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.     

Biology and treatment of malignant glioma

A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is amplified in an appreciable number. The loss or mutation of tumor-suppressor genes located on different autosomes may be associated with progression of malignant gliomas. The p53 tumor-suppressor gene (located on chromosome 17) is frequently associated with the loss of one allele in malignant gliomas, although a large number of malignant gliomas have no p53 mutations. Some of the latter tumors have an amplified murine double minute 2 (MDM2) gene, which suppresses p53 gene activity. Genetic material from chromosome 10 may also be lost, especially in glioblastoma multiforme. In addition to the aberrant expression of EGFR, another growth factor, platelet-derived growth factor, or PDGF (ligand and/or receptors) can be overexpressed, giving cells a selective growth advantage. The blood-brain barrier is substantially altered in malignant gliomas, resulting in cerebral edema. Therapy for malignant gliomas includes surgery, radiation therapy, and chemotherapy. Surgical resection that leaves little residual tumor produces longer survival than less vigorous surgery. Radiation therapy to a dose of at least 60 Gy is required to treat malignant gliomas. Increased survival beyond that produced by standard external radiotherapy requires much larger doses; interstitial radiotherapy permits such dosing. Radiosurgery is being tested. Chemotherapy with nitrosoureas is modestly useful but appears to benefit patients with anaplastic astrocytoma more so than those with glioblastoma.     

Surgical treatment of combined valvular disease in 680 patients

Between 1982 and May 1993, we operated on 680 patients with combined valvular disease. Previous operations were including closed mitral commissurotomy in 87, and bioprosthetic valve replacement in mitral position in 15. The types of combined valve disease included mitral valve disease combined with functional tricuspid regurgitation (FTR) (245), with organic tricuspid disease (OTD) (10); mitral and aortic disease (258), combined with FTR (128), and with OTD (39). The early mortality was 4.7% in total 2.4% and 6.1% respectively in MVR or DVR plus tricuspid procedures. The main cause of early death was low cardiac output syndrome. The late mortality was 2.6% pt-yr, congestive heart failure and coagulant-related hemorrhage were the predominant causes of late death. We considered that FTR is the outcome of right ventricle decompensation, while tricuspid valve must be actively inspected intraoperatively, and must be corrected completely. OTD can be successfully repaired in most patients. Myocardial protection should be emphasized, and continuous perfusion of cold blood cardioplegia and controlled reperfusion of warm blood contained mannitol have marked effect.     

Accelerated hyperfractionated radiotherapy combined with induction and concomitant chemotherapy for inoperable non-small-cell lung cancer--impact of total treatment time

PURPOSE: To determine the importance of fall characteristics, body habitus, function, and hip bone mineral density as independent risk factors for hip fracture in frail nursing home residents. SUBJECTS AND METHODS: In this prospective, case-control study of a single, long-term care facility, we enrolled 132 ambulatory residents (95 women and 37 men) aged 65 and older, including 32 cases (fallers with hip fracture) and 100 controls (fallers with no hip fracture). Principal risk factors included fall characteristics, body habitus, measures of functional assessment, and hip bone mineral density by dual-energy X-ray absorptiometry. RESULTS: In multivariate analysis, including only those with knowledge of the fall direction (n=100), those who fell and suffered a hip fracture were more likely to have fallen sideways (odds ratio 5.7, 95% confidence interval [CI] 1.7 to 18, P= 0.004) and have a low hip bone mineral density (odds ratio 1.9, 95% CI 0.97 to 3.7, P=0.06) than those who fell and did not fracture. When all participants were included (n=132) and subjects who did not know fall direction were coded as not having fallen to the side, a fall to the side (odds ratio 3.9, 95% CI 1.3 to 11, P=0.01), low hip bone density (odds ratio 1.8, 95% CI 1.03 to 3, P=0.04), and impaired mobility (odds ratios 6.4, 95% CI 1.9 to 21, P=0.002) were independently associated with hip fracture. Sixty-seven percent of subjects (87% with and 62% without hip fracture) had a total hip bone mineral density greater than 2.5 SD below adult peak bone mass and were therefore classified as having osteoporosis using World Health Organization criteria. CONCLUSIONS: Among frail elderly nursing home fallers, the preponderance of whom are osteoporotic, a fall to the side, a low hip bone density, and impairment in mobility are all important and independent risk factors for hip fracture. These data suggest that, among the frailest elderly, measures to reduce the severity of a sideways fall and improve mobility touch on new domains of risk, independent of bone mineral density, that need to be targeted for hip fracture prevention in this high-risk group.     

Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients

OBJECTIVE: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. DESIGN AND SETTING: Retrospective study in two German tertiary care treatment centres. PATIENTS: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. MAIN OUTCOME MEASURES: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. RESULTS: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). CONCLUSION: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.     

Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy

PURPOSE: To evaluate treatment tolerance in patients with and without the human immunodeficiency virus (HIV) who were undergoing treatment of anal cancer. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records of 62 patients with anal cancer who received radiation treatment. Seven patients had HIV, four of whom had acquired immunodeficiency syndrome. Fifty-five patients were HIV negative, including 11 patients identified as being at high risk for HIV infection whose status was unknown. RESULTS: Thirty of the 55 (55%) patients who were HIV negative required treatment breaks of a mean duration of 16.7 days. Four of those 55 (7%) patients required hospitalization. Three of 42 (7%) patients who were HIV negative receiving chemotherapy required chemotherapy dose reduction. All seven patients with HIV required treatment breaks of a mean duration of 21.7 days. Three of the seven (43%) patients required hospitalization. Four of the seven (57%) patients required chemotherapy dose reduction. CONCLUSION: Patients with HIV undergoing treatment of anal cancer have increased toxic reactions to chemoradiation. Treatment must be individually tailored on the basis of extent of disease and degree of compromise of the immune system.     

Surgical treatment methods in combined nasal deformities

Different classes of antibodies to polycyclic aromatic hydrocarbons (PAH) and immunogenicity of carcinoembryonic antigen (CEA) were investigated in breast cancer patients versus course. Prior to treatment, the levels of IgM, IgG and IgA antibodies to PAHs were 5.9, 7.7 and 32.5%, respectively. In cases of tumor regression, they were 13.8, 25.0 and 19.2%, while in those of progression-2.4, 2.8 and 12.8%, respectively. The immunogenicity of CEA, i.e. the power of forming circulating immune complexes, appeared to be higher in cases of tumor regression than in those of progression. CEA concentration in immune complexes exceeding 5ng/ml was observed in 24.0 and 15.1% of cases, respectively, while in whole serum, the concentration in excess of 10 ng/ml was in 8.0 and 42.4%, respectively.     

6-year experience of prenatal diagnosis in an unselected population in Oxford, UK

BACKGROUND: The benefits and harm associated with prenatal diagnosis are open to debate. We give a 6-year overview of the experience of one prenatal-diagnosis unit using a defined, unselected population. METHODS: All congenital malformations suspected prenatally and all congenital malformations, including chromosome anomalies, confirmed at birth were identified from the local Congenital Malformation Register. All fetuses or infants of women booked for delivery at the Oxford Women's Centre who had an OX postcode and date of delivery between 1991 and 1996 were eligible for the study. FINDINGS: 725 (2%) of 33,376 babies, were judged abnormal at delivery. 396 (55%) malformed fetuses and infants had been correctly identified prenatally. 174 fetuses had a suspected abnormality identified on scan and subsequently proved to be normal. 160 (92%) of these false-positive results were attributable to the reporting of so called ultrasound soft markers. Accuracy of ultrasound diagnosis was good for structural malformations. Ultrasound soft markers were responsible for a 4% increase in detection of malformations (from 51% to 55%) and a 12-fold increase in false-positive rate (one in 2332 to one in 188). 171 pregnancies (43% of prenatally diagnosed malformed babies) were terminated because of suspected abnormality. Suspicion of abnormality in these cases was first aroused after ultrasound scan in 136 (79%); chromosome analysis because of advanced maternal age, family history, or higher risk in biochemical screening test in 25 (15%); and molecular analysis of single gene defect because of family history in ten (6%). There was a 20% reduction in prevalence of conditions compatible with survival beyond the neonatal period because of termination of such pregnancies. INTERPRETATION: More than half of all malformed fetuses can be identified prenatally in routine practice, mostly following initial suspicion from ultrasound examination. Ultrasound soft markers lead to a small increase in detection of malformations but a large increase in false positives. Further research on the impact, including psychological, and value of markers is required to determine whether the benefits of reporting them exceeds the harm. Because methods and techniques continually change, ongoing surveillance of prenatal diagnostic services is vital.     

Pharmacokinetic MRI for assessment of malignant glioma response to stereotactic radiotherapy: initial results

The parasites of the red rockfish Sebastes capensis off northern Chile are described quantitatively for the first time and compared with those of congeneric species of the Northern Hemisphere as well as of other Chilean marine fishes. Sixteen species were recorded, including 8 ectoparasites (2 copepods, 2 isopods, 1 turbellarian, and 3 monogeneans) and 8 endoparasites (2 acanthocephalans, 3 digeneans, and 3 nematodes). The ectoparasites Lepeophtheirus chilensis and Caligus cheilodactylus, and the endoparasites Pseudopecoelus sp. and Corynosoma sp. were predominant. Eighty percent of the fishes harbored 3-6 parasite species. Four parasite genera new to the genus Sebastes were found in S. capensis, which also shares several parasite genera with its congeneric species from other geographic areas. However, in contrast to its congeners, S. capensis exhibits a lower helminth species richness, although when all the metazoan fauna is considered the species number and diversity are similar. When compared with other demersal fishes of the Chilean coast, S. capensis shows a high number of species and high parasite abundance. Diphtherostomum sp. and Gnathia sp. are new generic records for the parasite fauna of Chilean coast fishes and the finding of Paramicrocotyle sp., Neobenedenia melleni, and Interniloculus chilensis in this study represents a new geographical record for these parasites.     

高能聚束微波热疗联合沙培林胸腔注射治疗恶性胸水

Objective:The aim of the study was to evaluate the efficacy and toxiciiy of high power focused-beam microwave hyperthermia with intrapleural injection of Shapeilin for patients with malignant hydrothorax. Methods: Fifty-eight patients with malignant hydrothorax were divided into group A and group B randomly. All patients underwent indwelling pleural catheter and were treated by intrapleural injection of Shapeilin once three days. Treatment was composed of 3 times injection. Patients of group B received high power focused-beam microwave hyperthermia after injection of Shapeilin. Results: The response rate of group B (79.3%) was higher than that of group A (48.3%) (P < 0.05). Incidence of main adverse reactions, associated with Shapeilin, of two groups including fever and thoracodynia were similar (P > 0.05). Patients of group B didn't encounter severe toxicities of microwave hyperthermia. Conclusion: High power focused-beam microwave hyperthermia combined with intrapleural injection of Shapeilin is effective and tolerable for patients with malignant hydrothorax.     

Immunotoxin combined with chemotherapy for patients with AIDS-related non-Hodgkin's lymphoma

BACKGROUND: The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employing agents with independent mechanisms of action and nonoverlapping toxicity. This study was designed to test the feasibility and tolerance of combining low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients. METHODS: Previously untreated patients received low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, and vincristine (m-BACOD) on a 21- to 28-day schedule. Patients who did not have progressive disease by Cycle 3 received anti-B4-blocked ricin (anti-B4bR), a murine monoclonal antibody linked to modified ricin, 20 microg/kg/day for 7 days administered by continuous infusion on an outpatient basis. A repeat cycle of anti-B4-bR was administered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. Study endpoints were toxicity, development of human antimurine antibody (HAMA) and human antiricin (HARA), tumor response, and survival. RESULTS: Twenty-six of 44 patients received the immunotoxin therapy. Anti-B4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was observed in 8 patients (31%). The overall response rate was 57% (13 complete responses and 12 partial responses). The median survival for all patients was 8.9 months. CONCLUSIONS: This study demonstrates the safety and feasibility of using chemotherapy and immunotoxin therapies in combination and supports their further evaluation to improve the outcomes of patients with ARL.     

Surgical treatment of primary malignant chest wall tumours

Our objective was to infer the genetic model for the quantitative traits using a variety of methods developed in our group. Only a single data set was analyzed in any one analysis, although some comparison between data sets was made. In addition, the simulated model was not known during the course of the analysis. Basic modeling and segregation analyses for the five quantitative traits was followed by several simple genome scans to indicate areas of interest. A Markov chain Monte Carlo (MCMC) multipoint quantitative trait locus (QTL) mapping approach was then used to estimate the posterior probabilities of linkage of QTL to each chromosome simultaneously with trait model parameters, and to further localize the genes. Comparisons between the nuclear family and pedigree data sets indicated a greater power for QTL detection and mapping with the pedigree data sets. Even with the pedigree data, however, precise localization of the QTL did not appear to be possible using single replicate data sets. Two of the three genes with effects on trait Q1 were detected by the MCMC method.     

Pattern of failure in patients with inflammatory breast cancer treated by alternating radiotherapy and chemotherapy

BACKGROUND: Patients with inflammatory breast cancer have a high risk of developing a local recurrence and/or distant metastases. Treatment with combined chemotherapy and locoregional radiotherapy contributes to a decrease in both risks. This study presents treatment results and evaluates the pattern of failure when an alternating chemoradiotherapy schedule is used. METHODS: One hundred twenty-five patients with nonmetastatic inflammatory breast cancer were treated with an alternating schedule of radiotherapy and chemotherapy. All women recruited were younger than 70 years of age and had a T4d, histologically proven infiltrating carcinoma with N0 to N2 axillary disease. The protocol consisted of three cycles of induction chemotherapy with doxorubicin, vincristine, cyclophosphamide, methotrexate, and 5-fluorouracil followed by three series of locoregional radiotherapy, delivering a total dose of 65-75 Gy to the breast tumor. Five additional cycles of chemotherapy with 5-fluorouracil/doxorubicin/cyclophosphamide were to be administered in between the first two and after the third radiotherapy course. A 1-week gap was respected between each course of chemotherapy and each series of radiotherapy. RESULTS: Toxicity was moderate and this strategy proved feasible although most of the patients only received six instead of the eight planned cycles of chemotherapy. Eighty-two percent of the patients achieved a complete response at the end of the treatment. The cumulative 5-year local failure and distant metastasis rates were 27% and 53%, respectively. Assuming competing events, local failures, contralateral recurrences, and distant metastases were the first site of failure in 18%, 5%, and 38% of patients, respectively. The 5-year overall and disease free survival rates were 50% and 38%, respectively. The main prognostic factor was tumor size. CONCLUSIONS: Alternating high doses of radiotherapy and chemotherapy is a feasible treatment schedule and permits breast conservation. Disease free survival is comparable to that of recently published series. As the main causes of failure are distant metastases, higher dose chemotherapy should be evaluated, in an attempt to further improve overall survival.     

Paclitaxel in combination chemotherapy with radiotherapy in patients with unresectable stage III non-small-cell lung cancer

PURPOSE: The addition of combination chemotherapy to standard radiation therapy has improved treatment for locally unresectable non-small-cell lung cancer. In this phase II study, we evaluated the toxicity and efficacy of a novel chemotherapy regimen that included paclitaxel, cisplatin, and etoposide plus concurrent radiation therapy in this group of patients. PATIENTS AND METHODS: Thirty-three patients with previously untreated, unresectable stage III non-small-cell lung cancer (stage IIIA, 11 patients; stage IIIB, 22 patients) initially received two courses of chemotherapy, which included paclitaxel 135 mg/m2 by 1-hour infusion on day 1, cisplatin 60 mg/m/ intravenously (i.v.) on day 2, and etoposide 100 mg/m2 i.v. on days 1, 2 and 3. On week 6, radiation therapy (60 Gy in 30 fractions) was initiated in conjunction with two additional courses of chemotherapy: paclitaxel 135 mg/m2 i.v. by 1-hour infusion on day 1, cisplatin 5 mg/m2 i.v. on days 2- to 10, and etoposide 25 mg/m2 on days 1 to 10. RESULTS: This combined modality program was feasible and well tolerated by most patients. During the two courses of induction chemotherapy, grade 3 or 4 myelosuppression occurred in only six patients (18%). Esophagitis was common during combined modality therapy (grade 3, 10 patients; grade 4 five patients). Forty-two percent of patients had partial response after two courses of induction therapy, and 82% of patients had an objective response at completion of therapy. Twelve patients (36%) had a complete response. Nineteen patients remain progression-free at a median of 8 months; the median survival time has not been reached. CONCLUSION: This paclitaxel-containing combined modality therapy is feasible and highly active in patients with inoperable stage III lung cancer. Esophagitis is the most common severe toxicity with this program. Further studies with paclitaxel-containing combination regimens in patients with stage III non-small-cell lung cancer are indicated.     

Hyperfractionated radiotherapy combined with simultaneous chemotherapy in inoperable non-small cell lung cancer: a pilot study

Between March 1992 and February 1993, hyperfractionated radiotherapy (HRT) (1.2 Gy.fraction-1, twice a day, total dosage of 69.6 Gy) and simultaneous cisplatin (70 mg.m-2, 3rd and 23rd days of HRT) and etoposide (70 mg.m-2, 1-3rd and 20-23rd days of HRT) were applied to 27 patients with inoperable non-small cell lung cancer (NSCLC). Their Karnofsky performance statuses were 70-90%, and mean age was 52 (36-63). Two cases were stage II (one of the patients refused the operation and the other was medically inoperable because of insufficient ventilation), eight were stage IIIA and 17 were stage IIIB. No severe life-threatening grade IV acute toxicity findings were observed. Generally, acute side-effects were transient and did not require discontinuation of treatment. Tumour responses were as follows: complete response in six cases (23%); partial response in 19 cases (70%); and stable disease in two (7%). When complete response rates were compared according to stage, histological type, age group and weight loss, no statistically significant difference was found. Median overall and disease-free survival times were 14 months (95% confidence interval) (95% CI) 11-17 months and 10 months (95% CI 7-13 months), respectively. Twelve and 24 months overall and disease-free survival rates were 56 and 30%, and 36 and 24% respectively. No statistically significant difference was found in overall survival rates among epidermoid and nonepidermoid types, while the difference in disease-free survival was statistically significant. The acute and late complications of our HRT and simultaneous chemotherapy protocol were tolerable and the survival rates were encouraging.     

Surgical treatment of patients with open tibial fractures

Open tibial fractures are true surgical emergencies because of the risk of extensive infection to bone and devitalized soft tissue. The most serious consequence of open tibial fractures is osteomyelitis, which usually can be prevented by prompt surgical intervention within six to eight hours after injuries occur. Open tibial fractures often are the result of trauma from motor vehicle collisions, farm accidents, falls from heights, or gunshot wounds. Initial management of patients with multiple trauma injuries focuses on their life-threatening injuries before or during orthopedic surgical intervention for open tibial fractures. Orthopedic surgeons often work in collaboration with general, vascular, and plastic surgeons and perform multiple surgical procedures (eg, fasciotomy procedures for compartment syndromes, irrigation and debridement of wounds, application of external fixation devices, placement of intramedullary nails, possible limb amputations). The type and extent of open tibial fractures and soft tissue injuries determine the best treatment options for patients. Perioperative nurses should help patients focus on treatment choices for their open tibial fractures that ensure optimal surgical outcomes and maintain their quality of life.