Two patients having recurrent breast cancer with brain metastases well controlled with a gamma knife radio-surgery

We report two patients having recurrent breast cancer with brain metastases that was controlled well with a gamma knife radio-surgery. The patient is a 50-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy, and extended right lobectomy of the liver were performed in December 2001. Afterward, pleurodesis was carried out to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study revealed brain metastases with a diameter of 1 cm in her right midbrain in April 2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was started, and she took the regimen continuously. Another patient is a 56-year-old woman. She underwent skin sparing mastectomy with axillary lymph node dissection for right breast cancer in November 2002. Metastases to the base of her skull were found in October 2004, so a gamma knife radio-surgery was carried out. After the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In both of the two patients, the metastatic brain tumors have not shown growth so far and are under good control as of March 2006.     

Improved QOL with cancer chemotherapy in two patients with breast cancer suffering form carcinomatous pleurisy and carcinomatous peritonitis

One of the breast cancer patients introduced here suffered from recurrent carcinomatous pleurisy and the other from recurrent carcinomatous peritonitis. The patient with recurrent carcinomatous pleurisy was a 47-year-old female with stage IIIa breast cancer. She underwent a standard mastectomy and, following surgery, radiotherapy (50 Gy) and CAF therapy (30 mg of ADM, 1,800 mg of futraful and 100 mg of CPA, administered p.o.). Dyspnea occurred 4 years after surgery. Pleural exudate cytodiagnosis proved positive and the patient was diagnosed with carcinomatous peritonitis. Continuous thoracic cavity drainage was carried out, and 30 mg of ADM was injected into the thoracic cavity. CAF therapy was performed. The dyspnea and thoracic effusion disappeared. At present, after one year and 7 months, the patient is receiving outpatient treatment and remains under observation. The patient with recurrent carcinomatous pleurisy was a 43-year-old female. The breast cancer was detected in a diagnosis of metastasis to the axillary lymph nodes. An increased CA15-3 level and ascitic retention were observed postoperatively at 5 months. Following administration of 600 mg of UFT and 1,200 mg of MPA, the ascites decreased and improvement of the thickened peritoneum was noted. The CA15-3 level was also lowered. It is anticipated that chemotherapy for carcinomatous pleurisy and carcinomatous peritonitis will contribute to an improvement in patients' QOL.     

Distilled water pleurodesis for two breast cancer patients suffering from carcinomatous pleurisy

Pleural effusion of carcinomatous pleurisy is relatively common and a significant problem in recurrent breast cancer patients. It's very important to control it to keep a good quality of life for those patients. Two recurrent breast cancer patients, suffering from carcinomatous pleurisy and dyspnea due to pleural effusion, were treated with distilled water. As they have been treated with many kinds of hormonal therapy or chemotherapy for their several distant metastases, the performance status of these therapies has not been good. After one or two distilled water pleurodesis, pleural effusion was well controlled and dyspnea had disappeared. No adverse events, such as high fever and chest pain concerning this distilled water therapy were experienced. Taking its efficacy and a rarity of adverse events, distilled water plerodesis is a useful treatment for pleural effusion of carcinomatous pleurisy.     

Administration of docetaxel in cases of recurrent breast carcinoma with malignant pleural effusion controlled by intrapleural administration of OK-432

Docetaxel is an anti-tumor agent which promotes the congregation and stabilization of microtubules, there by preventing cell division. It is reported to have anti-tumor activity against breast or non-small cell lung carcinomas which have been resistant to other anti-tumor agents. On the other hand, it causes peripheral edema and effusion in the pleural or peritoneal cavities. Thus, pleural or peritoneal effusions, which require drainage have been considered to be contraindications for the administration of docetaxel. OK-432 is an agent which causes adhesion by evoking a local inflammatory reaction. We experienced two cases of recurrent breast carcinoma with malignant pleural effusion. We successfully managed their pleural effusion with the intrapleural administration of OK-432. Thereafter, we safely administered docetaxel, and obtained good outcomes. The present paper also discussed the synergistic action between these agents.     

Unilateral breast edema in two patients with malignant pleural effusion

Unilateral breast edema usually signifies an underlying pathology of the breast and prompts extensive investigations for the purpose of an early treatment. Although breast edema has been reported with other systemic etiologies, it has not been described in patients with lung cancer. We report two cases of unilateral breast edema occurring in patients with non-small cell lung cancer and ipsilateral pleural effusion. Mammography and ultrasound of the breast both revealed increased interstitial density suggestive of fluid retention without any underlying masses. We performed a therapeutic pleurocentesis on one patient for symptomatic relief, and there was simultaneous improvement of the breast edema. We postulate a possible pathophysiology for the association between breast edema and malignant pleural effusion. The principle of management when one encounters similar cases would be to treat the underlying pleural effusion.     

Adaptive radiotherapy of lung cancer patients with pleural effusion or atelectasis

Background and purpose

Changes in lung density due to atelectasis, pleural effusion and pneumonia/pneumonitis are observed in lung cancer patients. These changes may be an indication for adaptive radiotherapy in order to maintain target coverage and avoid increased risk of normal tissue complications.

Material and methods

CBCT scans of 163 patients were reviewed to score lung changes and find the incidence, the impact of geometric and dosimetric changes and the timing of appearance and disappearance of changes.

Results

23% of the patients had changes in the lung related to pleural effusion, atelectasis or pneumonia/pneumonitis. In 9% of all patients, the appearance or disappearance of a change introduced a shift of the tumor or lymph nodes relative to the spine >5 mm. Only major density changes affected the dose distribution, and 9% of all patients needed adaptive treatment planning due to density changes. In total, 12% of all patients did benefit from an adaptive treatment plan and in 85% of these patients, an atelectasis did change.

Conclusions

An adaptive strategy was indicated for 12% of the patients due to atelectasis, pleural effusion or pneumonia/pneumonitis. The predominant cause for adaptation was atelectasis. No systematic pattern in the appearance and disappearance of the changes were observed and hence weekly evaluation is preferable.     

胸腔内灌注紫杉醇与顺铂治疗乳腺癌恶性胸腔积液的疗效比较

目的观察比较胸腔灌注紫杉醇和顺铂治疗乳腺癌恶性胸腔积液的疗效、生活质量及不良反应。方法52例确诊为乳腺癌伴恶性胸腔积液患者,经胸膜腔置管引流术排尽积液后,随机分为紫杉醇组和顺铂组,每组26例。紫杉醇组：胸腔内注射生理盐水50ml＋紫杉醇120mg＋地塞米松10mg;顺铂组：胸腔内注射生理盐水50ml＋顺铂60mg＋地塞米松10mg。均为每周1次,连用2周,观察疗效及不良反应。结果紫杉醇组有效率为80．8％,顺铂组有效率61．5％（P〈0．05）。治疗后不良反应,胸痛以紫杉醇组明显（P〈0．05）,消化道反应以顺铂组明显（P〈0．05）。结论紫杉醇胸腔内注射治疗恶性胸腔积液疗效满意,不良反应可耐受。     

ATP生物荧光肿瘤体外药敏检测技术指导复发合并恶性胸腔积液的非小细胞肺癌的治疗

Objective: This study was aimed to research the feasibility of ATP-bioluminescence assay (ATP-TCA) guiding the treatment on recurrent non-small cell lung cancer (NSCLC) combined with malignant pleural effusion. Methods: We collected 30 pleural fluid samples which were approved to be positive by cytology from recurrent NSCLC patients. These cells were cocultured with chemotherapy medicines, single agent or drugs combination. Five drug concentrations, two parallel holes were examined in vitro for 4 days, the results were measured by adding luciferase-fluorescein working system and luminescence analyzer. We applied chemotherapy medicines according to the results in vitro of ATP-TCA. Results: There were differences among drug sensitivities of individuals. All the samples could be evaluated. Effective single drugs included cisplatinum, mitomycin C, doxorubicin, and pemetrexed disodium; sensitive drugs in the combination therapy were gemcitabine plus cisplatin, vinorelbine plus cisplatin, paclitaxel plus cisplatin, docetaxel plus cisplatin, and mitomycin C, vindesine plus cisplatin, in which gemcitabine + cispiatin (GEM + DDP) in vitro was the most efficient program. Conclusion: ATP-TCA in vitro sensitivity assay is rapid, reliable, and simple to guide the treatment of recurrent NSCLC with malignant pleural effusion, and can help clinicians to make the individual chemotherapy program.     

Analysis of 5-year survival among breast cancer patients with malignant pleural effusion receiving intrapleural OK-432 followed by adoptive transfer with cultured effusion lymphocytes

Since 1984, we have had 151 breast cancer patients with cytologically-confirmed malignant pleural effusions by local transfer of autologous effusion lymphocytes cultured with a conditioned medium containing T-cell growth factor after intrapleural preadministration of a streptococcal preparation, OK-432. Among the 81 patients given this therapy more than 5 years ago, 12 patients have survived 5 or more years, and 4 of these 12 have survived 10 (<) years. Patients surviving 5 (<) years had longer (32-204 months) disease-free periods, except for one patient with stage IV disease. Estrogen receptor was positive in 5 patients, negative in 1 patient, and unknown in 6 patients. Moreover, preceding or concomitant metastases in these patients were not life-threatening (6 chest-wall, 2 lymph-node, 4 lung, 3 bone metastases). In conclusion, effective therapy (effusion disappeared in all patients) and good control of concomitant metastases resulted in long-term survival of patients who had intrinsically better prognostic factors.     

Potential diagnostic value of methylation profile in pleural fluid and serum from cancer patients with pleural effusion

BACKGROUND: The objective of this study was to investigate the diagnostic value of methylation profiles for discrimination between malignant and benign pleural effusions. A secondary objective was to examine the concordance of methylation in samples of serum and pleural fluid. METHODS: The authors used methylation-specific polymerase chain reaction (MSP) analysis to examine the promoter methylation status of 4 genes in patients with pleural effusion: death-associated protein kinase (DAPK), Ras association domain family 1A (RASSF1A), retinoic acid receptor beta (RARbeta), and p16/INK4a. Pleural effusions were collected from 87 patients who had their diagnoses confirmed on cytologic and/or histologic examinations and clinical evolution. Pleural effusions were classified as malignant (n = 53 patients) or benign (n = 34 patients). RESULTS: Methylation was detected in serum from 45.3% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions, and it was detected in pleural fluid samples from 58.5% of patients with malignant pleural effusions and from 0% of patients with benign pleural effusions (P = .001). The sensitivity of MSP was greater than that of cytologic examination alone (39.1%; P = .001). When MSP was used together with cytologic examination, sensitivity increased to 69.8% (P = .001). CONCLUSIONS: Cell-free methylated DNA in pleural fluid can be detected in patients with neoplastic malignancy in a single extraction by thoracocentesis. Adequate management of the extracted pleural fluid can provide a rapid and reliable diagnosis in patients with pleural effusions who have suspected malignancy. MSP, used together with cytologic examination, may obviate the need for other invasive diagnostic tests.     

Local administration of adriamycin (ADM) for malignant pleural effusion and pericardiac effusion in breast cancer

We examined the efficacy, toxicity, and survival rate of patients treated with local administration of adriamycin (ADM) for malignant pleural effusion and pericardial effusion in breast cancer. From May 1996 to December 2002, we injected ADM into the pleural cavity for 21 courses and into the pericardial cavity for 2 courses in 18 patients. Thirteen patients showed CR (including 2 cases were injected into pericardial cavity), 2 PR, and 4 PD, and the overall response rate was 78.9%. Toxicities included nausea/vomiting, elevated fever, chest pain, and so on in 15 patients (83.3%). No severe toxicities, however, were observed. The overall survival rate after the removal of the drainage tube was 42.5% at 1 year and 16.5% at 2 years. The survival in patients with a first recurrence, and CR or PR was significantly better than other patients. We conclude that local administration of ADM is useful for treatment, without severe toxicities, of malignant pleural effusion and pericardial effusion in breast cancer.     

Intrapleural administration with OK-432 and cultured autologous pleural effusion lymphocytes for breast cancer patients with malignant pleural effusions: analysis of 84 patients over a 14-year period

Autologous effusion lymphocytes cultured for 9-13 days with condition medium containing T cell growth factor were transferred after intrapleural administration with a streptococcal preparation, OK-432, for 84 breast cancer patients with cytologically-confirmed malignant pleural effusion. Effusion disappeared in 54 and decreased in 19 patients, while in 11 the treatment was ineffective (87% response). A positive cytology changed to negative in 52 of 55 (95%) of the patients tested, while in 29 patients, effusion sample could not be obtained after treatment. A multivariate analysis of prognostic factors showed a significantly poorer prognosis in patients with the following concomitant metastases: liver metastasis, lung metastasis with lymphangitis carcinomatosa, and simultaneous bilateral effusions. Median survival time (MST) of all patients was 9 months (5-year survival: 18%). However, MST of the patients with limited disease (patients without liver metastasis, lymphangitis, or bilateral effusion) was 23 months (5-year survival: 28%). Ten patients survived more than 5 years (3 survived over 10 years) after the treatment among 46 patients with follow-up periods of > 5 years.     

乳腺癌术后胸膜转移性胸水TIL的细胞毒活性研究

目的：探讨乳腺癌术后胸膜转移引起的胸水中肿瘤浸润淋巴细胞（TIL）毒活性。方法：采用生物技术，提纯乳腺癌胸膜转移所致胸水中的TIL和相应的肿瘤细胞，经过一定时间诱导培养后，在7天，14天，21天和28天分别检测TIL对自身肿瘤细胞和K562细胞的杀伤活性。结果：该TIL对自身肿瘤细胞和K562细胞的杀伤活性无显性差异，21天时细胞毒活性最强。结论：TIL诱导培养21天时具有较强的生物活性，此时进行临床应用可能取得最佳疗效。     

卵巢癌合并右侧胸腔积液八例临床病理分析

为了探讨卵巢癌合并右侧胸腔积液的临床特点、发病规律及诊治策略,回顾性分析8例卵巢癌合并单纯右侧胸腔积液患者的临床资料.患者年龄43～66岁,中位年龄53岁,8例患者均接受手术治疗,7例为浆液性乳头状囊腺癌,1例为移行细胞癌,手术病理分期为Ⅰ C期1例,ⅢC期7例,随诊2例死于原发病,6例生存.初步研究结果提示,卵巢癌合并右侧胸腔积液多非肿瘤转移导致,应适当放宽手术指征,胸穿抽液改善呼吸症状后手术是其有效的治疗手段,效果显著,预后较好.     

The treatment of metastatic pleural effusion in breast cancer: report of 25 cases

We report our experience in the treatment of pleural effusion in 25 patients with metastatic breast cancer. Seventeen patients received initial systemic therapy and in 13 of them local intrapleural therapy was subsequently employed; the remaining 8 patients received local therapy only. Several modalities of local treatment were used: intrapleural chemotherapy with thiotepa and 5-fluorouracil; the production of pleural adhesion by the use of chest drainage alone or associated with instillation of sclerosing agents, such as nitrogen mustard or tetracycline. Of the 21 patients who were subjected to local therapy, 19 (90.5%) achieved an objective response (16 complete (76.2%) and 3 (14.34%) partial). Complete responses were observed exclusively in patients who had pleurodesis. Our data suggest that pleurodesis is the treatment of choice for neoplastic pleural effusion and that the use of tetracycline as a sclerosing agent is the most useful because of its availability, low cost and low morbidity.     

Two cases of recurrent breast cancer successfully treated with paclitaxel weekly therapy

The patients were a 57-year-old and a 38-year-old woman who had supraclavicular lymph node and multiple lung metastases from breast cancer. They were given 3 and 4 courses of paclitaxel (TXL) weekly therapy (80 mg/m2, day 1, 8, 15, repeated every 4 weeks). One patient had received docetaxel (TXT) and CEF therapy previously. There were no severe adverse effects except leukopenia, neutropenia and alopecia. The weekly TXL therapy brought complete remission against the supraclavicular lymph node and multiple lung metastases. The durations of the response to this weekly therapy were 15 and 5 months, respectively, and their effects have continued to the present. We believe that the weekly TXL therapy is a well-tolerated, feasible and safe administration schedule on an outpatient basis, and improves the patient's quality of life. Furthermore, we suggest the possibility of TXL being effective against both TXT and anthracycline-resistant breast cancer.     

Characterization of immune complexes from the pleural effusion of a breast cancer patient.

Pieural effusion from a patient with adenocarcinoma of the breast was precipitated by 50% ammonium sulfate and chromatographed on Sephadex G-200. The resulting elution profile consisted of three protein peaks. Fractions were monitored by immunodiffusion and assayed for [¹²⁵I]C1q binding activity (C1q B.A.). The first protein peak (eluted at the void volume) showed appreciable Clq B.A. and contained immunoglobulin G (IgG) and complement 3 (C3). These data suggested that antigen-antibody complexes were present in this macromolecular peak. IgG and C3 were also present in the second peak of Sephadex G-200 gel filtration while the third peak contained the albumin fraction. The known tumor-associated antigens, carcinoembryonic antigen, alpha-fetoprotein and ferritin, were not detected in any of the protein fractions as determined fay immunodiffusion analysis. The first Sephadex protein peak which contained high molecular weight IgG was chromatographed on Sepharose 6B. The second protein peak obtained by Sepharose filtration contained IgG and C3 and was further applied to a column of protein A-Septtarose. Proteins which bound to the immobilized protein A were dissociated with 2.5 M KSCN and chromatographed on Sepharose CL-6B under dissociating conditions. IgM rheumatoid factor, IgG and four putative antigens were obtained by these dissociation and chromatographic procedures. The isolated IgG exhibited a molecular weight of monomeric IgG and bound to saline extracts of malignant tissue at a greater amount titan to normal or benign breast extracts (p<0 05). The reactive breast tumor protein in these extracts was eluted in the molecular weight region of 67,000, as determined by gel filtration. The four putative pleural fluid antigens which dissociated from the IgG were tested for their ability to recombine with the isolated immunoglobulin. Results from radio-immunoprecipitation and the [¹²⁵I]C1q binding assay indicated that the putative antigens bound to the isolated IgG to form immune complexes.