Chemical pleurodesis for malignant pleural effusions

PURPOSE: To provide information about available agents for chemical pleurodesis. DATA SOURCES: A MEDLINE search (1966 to October 1992) was conducted using the terms malignant pleural effusion and pleurodesis. STUDY SELECTION: All articles containing references to patients with recurrent, symptomatic, malignant pleural effusions treated with chemical pleurodesis were selected and reviewed for pleurodesis regimen, number of patients treated, success rate (complete response), and adverse effects. The agents studied included doxycycline, minocycline, tetracycline, bleomycin, cisplatin, doxorubicin, etoposide, fluorouracil, interferon-beta, mitomycin-c, Corynebacterium parvum, methylprednisolone, and talc. DATA EXTRACTION: Independent extraction by three observers. RESULTS: Studies including a total of 1168 patients with malignant pleural effusions were reviewed for efficacy of the pleurodesis agent and studies including 1140 patients were reviewed for toxicity. Chemical pleurodesis produced a complete response in 752 (64%) of 1168 patients. The success rate of the pleurodesis agents varied from 0% with etoposide to 93% with talc. Corynebacterium parvum, the tetracyclines, and bleomycin had success rates of 76%, 67%, and 54%, respectively. The most commonly reported adverse effects were pain (265 of 1140, 23%) and fever (220 of 1140, 19%). CONCLUSIONS: Doxycycline and minocycline, with success rates of 72% and 86%, respectively, appear to be effective tetracycline-replacement agents in the few patients studied. Talc appears to be the most effective and least expensive agent; however, insufflation has the disadvantages of the expense of thoracoscopy and the usual need for general anesthesia. Bleomycin appears to be less effective than talc and the tetracyclines and is substantially more expensive.     

Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions

18 patients with malignant effusions were treated with continuous intraperitoneal, intrapleural, or intrapericardial infusion of methotrexate (MTX) 30 mg/m2 per d combined with simultaneous intravenous administration of leucovorin at a dose rate calculated to yield an equimolar concentration in the serum. In the serum the geometric mean steady-state MTX concentration was 0.95 microM, whereas it was 24 microM in the peritoneal, 213 microM in the pleural, and 434 microM in the pericardial cavities. Mean clearance was 6.6 ml/min from the peritoneal cavity, 2.6 ml/min from the pleural cavity, and 0.14 ml/min from the pericardial cavity. Leucovorin provided sufficient protection to allow the duration of infusion to be escalated from 24 to 120 h before myelosuppression was encountered. Marrow thymidylate synthetase activity was inhibited by an average of 46% compared to 86% inhibition in malignant cells in the effusions. Flow cytometric analysis showed no perturbation of the cell cycle phase distribution of marrow cells. All eight of the evaluable patients have responded: three received no other form of therapy, five also received systemic hormonal or chemotherapy. This study demonstrated that tumors confined to third space body fluids can be given very high concentration x time exposures to MTX with minimal systemic toxicity.     

Sclerotherapy for malignant pleural effusions: a prospective randomized trial of bleomycin vs doxycycline with small-bore catheter drainage

OBJECTIVES: The study's aims were to investigate the levels of gravidin, an endogenous phospholipase A2 inhibitor, in pregnancy and pre-eclampsia and to establish its effects on neutrophil function. STUDY DESIGN: Serum samples were collected from 9 nonpregnant, 15 preeclamptic, and 10 healthy pregnant women and assayed for free gravidin by enzyme-linked immunosorbent assay. Neutrophil phospholipase A2 and respiratory burst activities were determined in the presence of isolated free gravidin by cellular arachidonic acid release and superoxide anion production. RESULTS: Levels of free gravidin were higher in the healthy pregnant (36.1 +/- 5.5 ng/mL) and preeclamptic (17.8 +/- 2.8 ng/mL) groups than in the nonpregnant control group (3.9 +/- 0.5 ng/mL) and were significantly different between pregnancy groups (P <.01, Mann-Whitney U test). Free gravidin caused a concentration dependent decrease in N-formyl-methionyl-leucyl-phenylalanine-stimulated neutrophil arachidonic acid release (inhibitory concentration of 50% 25 nmol/L) and superoxide anion generation (inhibitory concentration of 50% 32 nmol/L). CONCLUSIONS: Circulating levels of free gravidin are reduced in pre-eclampsia compared with normal pregnancy. This may encourage an increase in the respiratory burst of neutrophils in pre-eclampsia and could contribute to the oxidative stress and vascular damage that characterize this disease.     

Surface treated large bore catheters with silver based coatings versus untreated catheters for extracorporeal detoxification methods

A population-based series of incident cases of malignant glioma were analyzed for mutations in the tumor suppressor gene p53. Exons 4-8 were screened using PCR-single-strand conformation analysis and confirmed through direct sequencing. Of 62 tumors analyzed, 12 (19%) contained mutations in p53: one 18-bp duplication in exon 5, five point mutations in exon 4, three point mutations in exon 7, two point mutations in exon 8, and a splice-site mutation at the exon 6/intron 7 boundary. In contrast to previous studies of malignant glioma, the prevalence of transversion mutations (56%) was higher than transition mutations (33%). A large proportion of transversion mutations occurred in exon 4, a region that is not routinely screened in gliomas. We present here an improved method for screening exon 4 (and other GC-rich regions) of p53 using PCR-single-strand conformation analysis. The high frequency of transversion mutations suggests a role for exogenous carcinogens in the etiology of malignant glioma.     

Experience with closed needle biopsy and pleural fluid cytology in the diagnosis of malignant pleural effusions in Yaounde, Cameroon

To determine and compare the efficacy of pleural fluid cytology and closed needle biopsy of the pleura in establishing the diagnosis of malignant pleural effusions in Yaounde, we reviewed the medical records of all consecutive patients with a pleural effusion admitted in unit B of the Chest Clinic of the Jamot Hospital between January 1990 and December 1994. Fifty four cases of malignant pleural effusion were diagnosed over this period. Closed needle biopsy of the pleura alone permitted a diagnosis of malignancy involving the pleura in 32 instances while cytological studies of pleural fluid provided a diagnosis in thirty six cases. A combination of both techniques was diagnostic in 48 (88.9%) patients. We recommend that both pleural fluid cytology and closed needle biopsy of the pleura be used concomitantly in the evaluation of pleural effusion for which malignancy is suspected.     

The risk of infection associated with intra-arterial catheters for cancer chemotherapy

OBJECTIVE: To determine the frequency of, and risk factors for, infections associated with intra-arterial catheters used for cancer chemotherapy. METHODS: Between September 1992 and September 1995, we conducted a surveillance study of all 807 intra-arterial catheters placed for chemotherapy at our center. The insertion site was disinfected with povidone iodine and alcohol, and the arterial catheter was placed using maximal sterile barrier precautions. Upon removal, all intravascular segments were submitted for semi-quantitative culture. RESULTS: No episodes of catheter-related bloodstream infection (95% confidence interval [CI95], 0%-1.6%) were observed. However, the risk of colonization (>15 colony-forming units) of arterial catheters was 15% (CI95, 12%-17%). Retrospective risk-factor analysis conducted on 224 intra-arterial catheters placed for chemotherapy in 1993 showed that colonization was associated significantly with duration of catheterization (median of 1 day for culture-negative catheters vs median of 4 days for culture-positive catheters, P<.001). Age, gender, prior radiotherapy, underlying cancer, neutropenia, and hypoalbuminemia were not associated with catheter colonization. CONCLUSION: Intra-arterial catheters for cancer chemotherapy placed under maximal sterile barrier precautions for a short period of time are associated with a very low risk of bloodstream infection.     

Improved endoscopic stenting for malignant dysphagia using Tygon plastic prostheses

BACKGROUND AND STUDY AIMS: Endoscopic palliative treatment of malignant esophageal stenosis using conventional plastic stents has been reported to be associated with a considerable risk of perforation. Stenoses with a distance of less than 2cm from the upper esophageal sphincter (UES) have generally been excluded from treatment. Using self-expandable metal stents, procedure-related complications are rare. However, the rates of late complications necessitating retreatment appear to be as high as those of plastic stents. This study describes our stent placement technique and our results using a modified Tygon plastic stent. PATIENTS AND METHODS: Over a two-year period, 71 consecutive patients with incurable malignant esophageal stenosis were prospectively studied. Tygon plastic stents of diameter 9-14 mm were individually tailored according to length and location of the stenosis. Prior to stenting, stepwise bougienage was performed, if necessary over several sessions. After endoscopic placement of a guide wire, the stent was inserted over a bougie without fluoroscopic monitoring. RESULTS: A total of 71 patients (54 men and 17 women, median age 69, range 34-93), were treated with Tygon plastic stents (14 mm: 19 patients; 12 mm: 50 patients; 9 mm: 2 patients). Median length of the strictures and of the stents were 7 (range 2-18) and 10 (range 6-25) cm, respectively. Four patients had an associated esophago-respiratory fistula. After a median of 2 (range 1-5) bougienage sessions, stent insertion was technically successful in all patients. Forty-one stents were placed across the cardia, 13 were positioned 0.5-1 cm below the UES. Three patients had to undergo retreatment within 24 hours because of pain or stent migration and the stents were repositioned or exchanged. No procedure-related perforation, hemorrhage or respiratory problems were observed. During a median follow-up of 63 (range 2-388) days, 82% of the patients died. Improvement or stabilization of dysphagia allowing for oral nutrition could be achieved in 89%. Dislocation occurred in eight patients, bolus obstruction in five patients and tumor overgrowth in four patients. Three of the four fistulas could be covered by the stent. In one patient with a fistula located at the level of the UES, a stent was placed but migrated after 5 days. Overall, 27 patients (38%) required reinterventions, mainly for dysphagia or nutritional problems. CONCLUSIONS: In our experience, Tygon plastic stents with a diameter of 9-14 mm can be safely placed after stepwise, less extensive bougienage. Effective palliation is possible even for lesions located close to the UES. Perforation can be avoided. Reintervention rates seem to be comparable to those seen with self-expanding metal stents.     

Accelerated radiotherapy regimen for malignant gliomas using stereotactic concomitant boosts for dose escalation

Parvovirus B19 (PV B19) infection was investigated in 29 pregnant women with fetal hydrops, after exclusion of feto-maternal incompatibility within red blood cell antigens, TORCH infections, feto-maternal hemorrhage and genetics reasons. The active viral infection was detected in 9 women (31%) by PCR amplification of DNA B19; in 2 of them IgM and IgG, in 1 IgM and in 4 IgG antibodies were also present. In 6 women (20%) IgG antibodies were only found, but not IgM and DNA B19, which confirmed infection in the past. In addition in 9 cases DNA B19 was evaluated in the fetal blood. The results in the mothers and their fetuses were concordant (4 positive, 5 negative). Our conclusion is that in nonimmune hydrops fetalis, PV B19 infection should be based on the viral DNA evaluation in the blood of mother (or fetus). IgM antibodies, in time of fetal disorders, might not be detected.     

胸腔置管白介素-2联合顺铂治疗恶性胸腔积液的临床观察

Objective: The aim of our study was to explore the short-term effects and complication of interleukin-2 (IL-2) combining with Cisplatin in the treatment of malignant hydrothorax. Methods: Sixty-two cases patients with malignant hydrothorax were randomly divided into two groups. Observation group was 31 examples, thoracic cavity injection IL-2 and Cisplatin; 31cases in control group using Cisplatin alone intra-thoracic injection. The regime of every week for 1-4 weeks was used to observe short term effects and complications. Results: The total response rate in observe group was higher than that in control group (90.3% vs. 68.1%), which had statistically significant difference (P ＜ 0.05). The complications included gastrointestinal tract reaction, bone marrow inhibition, chest pain and fever. The incidence rates of chest pain and fever in observe group was slightly higher than that in control group, but there was no statistically significant difference (P ＞ 0.05). Conclusion: The IL-2 combining with Cisplatin intra-thoracic injection for malignant hydrothorax has the features of good therapeutic effects and slight poisonous side effects, which is worth to be used in clinic.     

Treatment of malignant pleural effusions with a combination of bleomycin and tetracycline. A comparison of bleomycin or tetracycline alone versus a combination of bleomycin and tetracycline

BACKGROUND: Treatment of patients with malignant pleural effusions is mostly palliative. Tetracycline and bleomycin are the two most commonly used agents for the treatment of pleurodesis. In this study, the authors used a combination of the two drugs for this particular purpose. METHODS: Sixty patients with massive malignant pleural effusions were divided in 3 equal groups in a simple randomized manner. Tetracycline (20 mg/kg [maximum of 2 g] in 50 mL of normal saline) was administered through a chest tube in Group 1. Group 2 received bleomycin (1 U/kg [maximum of 60 U] in 50 mL of normal saline). Group 3 received the above 2 preparations (tetracycline, 20 mg/kg [maximum of 2 g] in 40 mL of normal saline and bleomycin, 1 U/kg [maximum of 60 U] in 30 mL of normal saline) instilled one after the other, while the chest tube was clamped for 5 minutes in the interim. Follow-up examinations were performed at 7 days, 30 days, 60 days, 90 days, and 6 months. RESULTS: There was no significant difference in the complete response rate of the 3 groups during the first 4 months. At the end of the study, Group 3 had a significantly higher complete response rate (70%) compared with Groups 1 and 2 (35% and 25%, respectively) (P = 0.02). CONCLUSIONS: The response to use of a combination of bleomycin and tetracycline for the treatment of patients with pleurodesis is superior to that achieved by either of these agents used alone.     

Experimental grounds for using chlorin e6 in the photodynamic therapy of malignant tumors

The toxicity, pharmacokinetics and antitumour effect of chlorin e6 after light irradiation were studied. The LD50 value of chlorin e6 in C3H mice is 189 +/- 9 mg kg-1 and in Wistar white rats is 113 +/- 18 mg kg-1 14 days after intraperitoneal injection. The concentration of chlorin e6 in blood, liver, kidney, spleen and tumors (sarcoma M-1 and sarcoma 45) of the rats was determined by a fluorescence method, 3, 6, 12, 18, 24, 48 and 72 h after administration at a dose of 10 mg kg-1. For this purpose, chlorin e6 was extracted from tissues by the detergent Triton X-100. The depth of necrosis in sarcoma 45, the regression rate of sarcoma M-1 and the animal cure rate were evaluated after chlorin e6 administration at doses of 1-10 mg kg-1 and subsequent irradiation with krypton laser light. Depending on the dose and the time interval between chlorin e6 injection and irradiation, the depth of necrosis in sarcoma 45 varied from 5.0 to 15.0 mm. The cure rate of the animals with sarcoma M-1 varied from 10% to 60%. The antitumor effect was directly proportional to the chlorin e6 dose and light energy exposure and inversely proportional to the time interval between photosensitizer injection and irradiation.     

Fallibility of persistent blood return for confirmation of intravascular catheter placement in patients with hemorrhagic thoracic effusions

Two patients are described with hemorrhagic thoracic effusions who required central venous catheterization. Presumed subclavian and internal jugular vein cannulation, ipsilateral to the hemorrhagic thoracic effusions, was confirmed by the operators in each case by the persistent aspiration of blood. Subsequent clinical and radiologic evaluation revealed that the vascular catheters were introduced into the pleural space. In both individuals, the persistent aspiration of extravascular hemorrhagic fluid mimicked intravascular catheter positioning. Physicians treating patients with hemorrhagic thoracic effusions need to be aware of this potential complication that can result in the delayed resuscitation of hemodynamically unstable patients.     

Prospective study of infective complications in newborns with fine silicone catheters used for parenteral nutrition infusion

OBJECTIVE: Percutaneous silastic central venous catheters have contributed to improve the care of neonates. They are quite safe; however, sometimes complications occur, with infections being the most frequent. A prospective study was undertaken in our NICU to know the rate of catheter-related sepsis, the influence of the duration of catheterization, the predominant portal of entry and the microorganisms isolated. PATIENTS AND METHODS: Fifty-two catheters were analyzed. Cultures were obtained once a week by aspiration from the catheter hub, the luer-lock connection and parenteral nutrition solution directly from the bag. If sepsis was suspected, blood cultures were obtained from a different vein. The tip was cultured after catheter withdrawal by the semiquantitative technique of Maki. RESULTS: Nineteen catheters (36.5%), 19 luer-lock connections (21.3%) and 7 parenteral nutrition solutions were colonized. We found a significant increase of the rate of colonization after the catheter had been in place 3 weeks or more (p < 0.05). Coagulase negative Staphylococcus was isolated in 75.7% of the samples. The rate of catheter related sepsis was 15.4% (7/8 caused by coagulase negative Staphylococcus). CONCLUSIONS: Catheter related sepsis may be more frequent than expected it colonization of the catheter were analyzed systematically. Screening catheter colonization allows an earlier diagnosis of pathogens if sepsis develops. Finally, we believe that the use of sterile techniques to handle the catheter and connections will further decrease catheter related infections.     

愕部恶性肿瘤近距离放疗中义齿基托布源器的设计与制作

目的:设计与制作含有~125I放射性粒子的义齿基托布源器,应用其对腭部腺源性恶性肿瘤进行术后放射性粒子近距离放射治疗.方法:42例硬腭或软硬腭交界处的腺源性恶性肿瘤患者,经局部手术切除术后佩戴含有~125I放射性粒子的义齿基托布源器进行近距离放疗.义齿基托布源器由3部分组成:组织面为树脂层,用于容纳放射性粒子;磨光面为钴铬合金层,用于对正常组织提供放射性防护;还有起固位作用的卡环.义齿基托布源器的固位与稳定参考可摘局部义齿的设计原则设计,如患者伴有上颌牙齿缺失,则可在布源器上排列人工牙,以同期恢复患者咀嚼功能.结果:42例患者佩戴使用义齿基托布源器良好,放射性粒子没有移位、丢失.随访12~72个月,照射区组织愈合良好,恶性肿瘤未见复发.所有患者均未观察到严重并发症.结论:放射性粒子治疗腭部恶性肿瘤时,义齿基托布源器有利于实现靶区治疗,该方法具有方便、有效,并对周围正常组织具有放射性防护的特点.     

The safety of reusing ablation catheters with temperature control and the need for a validation protocol and guidelines for reprocessing

The objective of this study was to evaluate the safety of reusing ablation catheters with temperature control, which has not previously been reported. A review of previously conducted studies on the feasibility of reusing electrode catheters is also presented. From September 1994 to December 1997, 74 deflectable ablation catheters with temperature control (Cordis-Websters and Osypkas) were used during mean 7.6 +/- 8.0 ablation sessions. The catheter tests included visual inspection for surface defects using a magnification glass, impedance measurements, evaluation of the catheter deflection capability, and the integrity of the thermistor and thermocouple. The catheters were sterilized by Sterrad after each use. A total of 41 catheters were rejected after an average 9.1 +/- 8.8 uses (range 1-31). The main reasons for rejection were inaccurate temperature measurements by the thermistor or thermocouple (19%), breakage of or defect in the internal pulling wire (12%), loss or disturbance of electrogram (9%), and loss of deflection capability (8%). The reuse of the catheters has not resulted in any major catheter failures or any major adverse clinical complications. There were no local or systemic infections. It can be concluded that these types of ablation catheters will sustain repeated uses and resterilizations without untoward harm to the patient provided that a thorough validation protocol and guidelines for quality control and rejection of catheters are used. There seems to be no rational for setting a limit for the number of reuses, since most failures occurred at any time of reuse.     

Phase I study of topotecan for pediatric patients with malignant solid tumors

PURPOSE: To determine the dose-limiting toxicity and potential efficacy of topotecan in pediatric patients with refractory malignant solid tumors. PATIENTS AND METHODS: In this phase I clinical trial, 27 patients received topotecan 0.75-1.9 mg/m2 by continuous intravenous infusion daily for 3 days. Fifty-three treatment courses were given to these patients. RESULTS: Myelosuppression was the dose-limiting toxicity at levels of 1.3 to 1.9 mg/m2 for 3 days, requiring significant support with transfused packed RBCs and platelets. Myelosuppression was variable in severity at the 1.0-mg/m2 dosage level; thus, additional patients were treated with this dosage, followed by human recombinant granulocyte-colony stimulating factor (G-CSF). Other toxicities were not significant. One patient with neuroblastoma had a complete response that lasted for 8 months. Stable disease activity was recorded for other patients with neuroblastoma, rhabdomyosarcoma, and islet cell carcinoma. Pharmacokinetic studies showed that topotecan plasma concentrations ranged from 1.6 to 7.5 ng/mL during infusions of 1.0 mg/m2/d, and that there was a biphasic plasma distribution with a mean terminal half-life of 2.9 +2- 1.0 hours. CONCLUSION: Topotecan is a promising anticancer agent that deserves phase II testing in pediatric solid tumors. We recommend that pediatric phase II topotecan trials use 1.0 mg/m2/d for 3 days as a constant intravenous infusion, followed by G-CSF for 14 days, and that these treatment courses be repeated every 21 days.