Sterilized talc pleurodesis for malignant pleural effusions: a Phase II study for investigational new drug application in Japan.

BACKGROUND: Malignant pleural effusion is a commonly seen complication of malignancies such as lung and breast cancers. In Western countries, talc is frequently used as a standard therapeutic agent (pleurodesis agent) with the aim of alleviating symptoms including dyspnea and chest pain. Talc is not recognized as a pleurodesis agent in Japan. The aim of this study was to verify the efficacy and safety of sterilized talc (NPC-05) for the introduction of talc in Japan. METHODS: The study was a single-arm, open-label, investigator-initiated trial conducted jointly at six institutions. The subjects were 30 patients with malignant pleural effusions. A solution of 4 g NPC-05 suspended in 50 ml physiological saline was instilled into the pleural space to perform pleurodesis. RESULTS: The efficacy of NPC-05 for pleural adhesion 30 days after pleurodesis was 83.3% (25/30 cases). Amelioration of dyspnea and pain (chest pain) was seen. Commonly seen adverse effects were increased C-reactive protein (CRP) and fever. Nearly all adverse events were phenomena previously reported as adverse effects of talc. No acute respiratory distress syndrome (ARDS) or other serious side effects occurred. CONCLUSION: The efficacy and safety of NPC-05 for malignant pleural effusion in Japanese patients was verified, and the clinical outcomes with talc were confirmed to be the same as previously reported in other countries. There is thought to be a high level of need for this agent in the treatment of malignant pleural effusion in Japan.

MEK and PI3K catalytic activity as predictor of the response to molecularly targeted agents in triple-negative breast cancer.

Hyper-activation of the MAPK and PI3K-AKT pathways is linked to tumour progression in triple-negative breast cancer (TNBC). However, clinically effective predictive markers for drugs targeted against protein kinases involved in these pathways have not been identified. We investigated the ability of MEK and PI3K catalytic activity to predict sensitivity to trametinib and wortmannin in TNBC. MEK and PI3K activities correlated strongly with each other only in cell lines showing wortmannin-specific sensitivity, as shown by a linear regression curve (R = 0.951). Accordingly, we created a new parameter that distinguishes trametinib and wortmannin sensitivity in vitro and in vivo. Our findings suggest that the catalytic activities of MEK and PI3K might predict the response of TNBC to trametinib and wortmannin.

[Antibacterial activity for clinical isolates from pediatric patients of clavulanic acid/amoxicillin (1: 14) -outcomes of special drug use investigation on antibacterial activity (annual changes)].

As a special drug use investigation, we monitored and assessed trends in antibacterial activity of clavulanic acid/amoxicillin (1:14) (hereafter, "CVA/AMPC (1:14)") and other antimicrobial agents for clinical isolates from pediatric patients with otitis media or respiratory, skin, and urinary tract infections. Against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis isolated and identified from otorrhea, epipharynx and rhinorrhea of pediatric patients with otitis media, the MIC90s of CVA/AMPC (1:14) in five years between 2006-2010 were 1 microg/mL for S. pneumoniae and 8 microg/mL for H. influenzae and 0.25-0.5microg/mL for M catarrhalis. The changes of MIC90s of CVA/AMPC (1:14) for penicillin-resistant S. pneumoniae (PRSP) and beta-lactamase non-producing H. influenzae were two times, and no decrease in drug susceptibility was found in the period of the present investigation. In addition, the MIC changes of other antimicrobial agents for these three organisms were approximately two to four times as well. Against organisms isolated and identified from pus, sputum, pharynx, skin and urine of pediatric patients with respiratory, skin, and urinary tract infections, the MIC90s of CVA/AMPC (1:14) in four years between 2008-2011 were 1 microg/mL for S. pneumoniae, < or =0.06microg/mL for penicillin susceptible S. pneumoniae (PSSP) without any change, 0.5-1 microg/mL for penicillin intermediate resistant S. pneumoniae (PISP) with a twofold change and 1 microg/mL for PRSP with no change. The MIC90s of CVA/AMPC (1:14) were 2-8 microg/mL for S. aureus with a fourfold change, 2 microg/mL for methicillin-sensitive S. aureus without any change, 4-8 microg/mL for H. influenzae with a twofold change. Against beta-lactamase non-producing H. influenzae, MIC90s of CVA/AMPC (1:14) were 1 microg/mL for beta-lactamase negative ampicillin susceptible (BLNAS), 8 microg/mL for beta-lactamase negative ampicillin resistant (BLNAR), showing no change. Neither Streptococcus pyogenes or Klebsiella pneumoniae demonstrated any change and M. catarrhalis and Escherichia coli showed twofold changes of MIC90s of CVA/AMPC (1: 14). In the present investigation conducted to monitor annual changes in antibacterial activity intended for pediatric patients with otitis media or other infections, there was no significant change in antibacterial activity of CVA/AMPC (1: 14).

Case report: Electrocardiographic changes in pembrolizumab-induced fatal myocarditis.

Immune checkpoint inhibitor (ICI)-induced myocarditis is rare but fatal. Because of the rapid course of ICI-induced myocarditis, understanding of clinical course is only possible through information from case reports. We report a case of pembrolizumab-induced myocarditis in which we were able to document the course of electrocardiographic changes from onset to death. A 58-year-old woman with stage IV lung adenocarcinoma, who had completed her first cycle of pembrolizumab, carboplatin, and pemetrexed, was admitted with pericardial effusion. She underwent pericardiocentesis after admission. A second cycle of chemotherapy was administered 3 weeks after the first cycle. Twenty-two days after admission, she developed a mild sore throat and tested positive for SARS-CoV-2 antigen. She was diagnosed with mild coronavirus disease 2019 (COVID-19), isolated, and treated with sotrovimab. Thirty-two days after admission, an electrocardiogram showed monomorphic ventricular tachycardia (VT). Suspecting myocarditis caused by pembrolizumab, the patient was started on daily methylprednisolone after coronary angiography and endocardial biopsy. Eight days after the start of methylprednisolone administration, she was considered to have passed the acute stage. However, four days later, R-on-T phenomenon triggered polymorphic VT and she died. The impact of viral infections such as COVID-19 on patients be treated with immune checkpoint inhibitors is still unknown and we need to be careful with systemic management after viral infections.

Sensitive and specific new enzyme-linked immunosorbent assay for N-ERC/mesothelin increases its potential as a useful serum tumor marker for mesothelioma.

BACKGROUND: Because mesothelioma initially progresses on the surface of the pleura and peritoneum without forming masses, it has been difficult to diagnose at an early stage. It would be very useful to identify a tumor marker that could be used for screening to enable more diagnoses to be made at an early, treatable stage. MATERIALS AND METHODS: We had previously identified N-ERC/mesothelin as a potential biomarker for mesothelioma. In the current work, we used a newly developed ELISA system to gain data on N-ERC/mesothelin levels in various clinical settings. A total of 102 healthy volunteers were recruited. In addition, 39 patients were diagnosed with mesothelioma, 53 patients were diagnosed with diseases that should be distinguished from mesothelioma, and 201 subjects were diagnosed with asbestos-related nonmalignant diseases (including simple exposure to asbestosis) who were treated at any of the cooperating hospitals were enrolled. RESULTS: Serum N-ERC/mesothelin levels measured by a new ELISA system showed that the median values from patients with mesothelioma were extremely high compared with levels obtained from other patients. Analysis in terms of histologic type showed that serum levels of N-ERC/mesothelin were elevated in epithelioid type mesothelioma, especially. In four important models of clinical settings, the sensitivity and specificity of N-ERC/mesothelin were about 71% to 90% and 88% to 93%, respectively. CONCLUSION: N-ERC/mesothelin is a very promising tumor marker for mesothelioma, especially epithelioid mesothelioma.

Narrow band imaging applied to pleuroscopy for the assessment of vascular patterns of the pleura.

BACKGROUND: Narrow band imaging (NBI), which enhances blood vessels, is a new endoscopic technology for diagnosing malignancies, but it has not been investigated for pleuroscopy. OBJECTIVES: To evaluate the efficacy of NBI applied to pleuroscopy for detecting malignant lesions by assessing vascular patterns of the pleura. METHODS: From May 2006 to September 2008, 45 patients with undiagnosed pleural ef-fusion underwent pleuroscopy using a pleura-videoscope with white light (WL) and NBI under local anesthesia. For this prospective study, 73 biopsy specimens were obtained from sites where images under both WL and NBI were recorded and classified regarding vascular patterns. RESULTS: Of the 73 lesions, WL showed blood vessels in 32 lesions, and NBI in 52 lesions (WL vs. NBI; p = 0.0014). The accuracy, sensitivity and specificity in the detection of irregular vascular patterns, e.g. blood vessels with irregular caliber or punctate vessels indicating malignant lesions, were 60.3, 76.5 and 55.4% in WL, and 80.8, 85.3 and 76.9% in NBI, respectively, resulting in a significant increase in NBI (p = 0.0106 for accuracy and p = 0.0494 for specificity). For flat lesions, NBI revealed a higher accuracy rate (90.6%) in the detection of irregular vascular patterns indicating malignant lesions. CONCLUSION: Our study demonstrated that NBI applied to pleuroscopy displayed blood vessels significantly better than WL. NBI was useful to detect irregular vascular patterns suggesting malignant lesions, especially for flat lesions. Therefore, NBI was considered useful in the selection of optimal biopsy sites by assessing vascular patterns.

Combination of exercise and losartan enhances renoprotective and peripheral effects in spontaneously type 2 diabetes mellitus rats with nephropathy.

OBJECTIVES: We assessed the renal and peripheral effects of chronic exercise in a rat model of diabetic nephropathy and the benefits of combined exercise and losartan. METHODS: Heminephrectomized Goto-Kakizaki rats were divided into four groups: (i) no exercise (control); (ii) exercise with treadmill running; (iii) losartan; (iv) exercise plus losartan, and the rats were treated for 12 weeks. RESULTS: Losartan and exercise plus losartan significantly decreased systolic blood pressure (SBP). Exercise, exercise and losartan, and losartan blunted the increases in proteinuria. The index of glomerular sclerosis (IGS) and the relative interstitial volume of the renal cortex were significantly improved in the exercise, exercise and losartan, and losartan groups. The IGS, expressions of ED-1 and alpha-smooth muscle actin in the glomerulus were the lowest, and the number of Wilms' tumour was the highest in the exercise plus losartan group. The endurance, the proportion of type I fibre and capillarization in the extensor digitorum longus muscle were greater in the trained groups. CONCLUSION: These results suggest that both exercise and losartan have renoprotective effects, and the combination of exercise and losartan provided greater renoprotective effects than losartan alone, and may affect macrophage infiltration, mesangial activation, and podocyte loss in this model of diabetic nephropathy. It is also suggested that exercise has a specific renoprotective effect that is not related to SBP reduction, and can enhance endurance without renal complications.

Preventive Effects of Lamotrigine in Bipolar II Versus Bipolar I Disorder.

OBJECTIVE: The preventive effects of mood stabilizers on recurrence/relapse in bipolar disorders have been investigated mostly in bipolar I disorder (BPI) patients, with limited reports on bipolar II disorder (BPII) patients. Here, we conducted an explorative data analysis to investigate whether the preventive effect of lamotrigine on recurrence /relapse in BPII is better than in BPI. METHODS: Data from Japanese patients with a diagnosis of BPI or BPII according to DSM-IV-TR were analyzed in an open-label, noninterventional, naturalistic, prospective postmarketing surveillance study of lamotrigine. This study was carried out from October 2011 to November 2014, and each patient was observed for 1 year. The time to recurrence/relapse of mood episodes after commencement of lamotrigine treatment was evaluated as a primary endpoint. Kaplan-Meier curves were generated to compare the time to recurrence/relapse of mood episodes in BPI with in BPII using a log-rank test. RESULTS: Lamotrigine was associated with a significantly longer time to recurrence/relapse of mood episodes in BPII than in BPI (log-rank test, P = .0103). Lamotrigine also prolonged time to recurrence/relapse of mania-related episodes, including hypomanic episodes, more in BPII than in BPI (P = .0110). CONCLUSIONS: Although the preventive effect of lamotrigine on recurrence/relapse of mood episodes in BPI has been established in a variety of clinical studies, the present study suggests that lamotrigine may be more suitable for maintenance treatment in BPII than in BPI.

Assessment of safety and efficacy of lamotrigine over the course of 1-year observation in Japanese patients with bipolar disorder: post-marketing surveillance study report.

BACKGROUND: A post-marketing surveillance (PMS) study was conducted with a 1-year observation period to assess the safety and efficacy of lamotrigine in routine clinical practice in patients with bipolar disorder (BD). PATIENTS AND METHODS: Central enrollment method was used to recruit patients diagnosed with BD who were being treated for the first time with lamotrigine to prevent the recurrence/relapse of BD mood episodes. Adverse drug reactions (ADRs) and recurrence/relapse were assessed. Improvement of mania and depression was also assessed using the Hamilton's Rating Scale for Depression (HAM-D) and the Young Mania Rating Scale (YMRS) at treatment initiation, 4-6 months post treatment initiation, and 10-12 months post treatment initiation. RESULTS: A total of 237/989 patients (24.0%) reported ADRs, most commonly rash (9.1%), and the incidence of serious ADRs was 3.3% (33/989 patients). Skin disorders occurred in 130 patients (13.1%), mostly within 8 weeks post treatment. A total of 237/703 patients (33.7%) experienced recurrence/relapse of mood episodes. The 25th percentile of the time to recurrence/relapse of mood episodes was 105 days. Remission of depression symptoms (HAM-D ≤7) occurred in 147/697 patients (21.1%) at treatment initiation, rising to 361 patients (67.4%) at 10-12 months post treatment. Remission of manic symptoms (YMRS ≤13) occurred in 615/676 patients (91.0%) at treatment initiation, rising to 500 patients (97.3%) at 10-12 months post treatment. CONCLUSION: The results of this PMS study suggest that lamotrigine is a well-tolerated and effective drug for preventing recurrence/relapse of BD in clinical practice.

Intractable pneumothorax managed by talc pleurodesis and bronchial occlusion with spigots.

Three cases of inoperable secondary spontaneous pneumothorax were diagnosed in patients with chronic obstructive pulmonary disease. Two cases initially underwent bronchial occlusion with endobronchial Watanabe spigot (EWS), while one underwent talc poudrage with pleuroscopy. As air leaks were not stopped completely in all cases with the initial procedures, we performed additional interventional treatments: pleuroscopic talc poudrage in cases when bronchial occlusion was performed first; and bronchial occlusion with EWS for a case that initially underwent talc pleurodesis. The air leaks ceased in all cases without complication. We successfully removed chest tubes 2-10 days after secondary procedure, which was 10-23 days after the first procedure. The combination of talc pleurodesis and bronchial occlusion with EWS, when a single, initial interventional treatment fails, can be considered in cases of intractable, inoperable secondary pneumothorax.

Human Lipocalin-Type Prostaglandin D Synthase-Based Drug Delivery System for Poorly Water-Soluble Anti-Cancer Drug SN-38.

Lipocalin-type prostaglandin D synthase (L-PGDS) is a member of the lipocalin superfamily, which is composed of secretory transporter proteins, and binds a wide variety of small hydrophobic molecules. Using this function, we have reported the feasibility of using L-PGDS as a novel drug delivery vehicle for poorly water-soluble drugs. In this study, we show the development of a drug delivery system using L-PGDS, one that enables the direct clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), a poorly water-soluble anti-cancer drug. In the presence of 2 mM L-PGDS, the concentration of SN-38 in PBS increased 1,130-fold as compared with that in PBS. Calorimetric experiments revealed that L-PGDS bound SN-38 at a molecular ratio of 1:3 with a dissociation constant value of 60 µM. The results of an in vitro growth inhibition assay revealed that the SN-38/L-PGDS complexes showed high anti-tumor activity against 3 human cancer cell lines, i.e., Colo201, MDA-MB-231, and PC-3 with a potency similar to that of SN-38 used alone. The intravenous administration of SN-38/L-PGDS complexes to mice bearing Colo201 tumors showed a pronounced anti-tumor effect. Intestinal mucositis, which is one of the side effects of this drug, was not observed in mice administered SN-38/L-PGDS complexes. Taken together, L-PGDS enables the direct usage of SN-38 with reduced side effects.

Endobronchial ultrasonography in the diagnosis and treatment of relapsing polychondritis with tracheobronchial malacia.

Relapsing polychondritis (RP) with tracheobronchial involvement has a poor prognosis, and a delay in diagnosis increases morbidity and mortality; however, the diagnosis is difficult to make. Endobronchial ultrasonography (EBUS) revealed changes in the tracheobronchial cartilage in two patients who met the criteria for RP, and facilitated the diagnosis. In these cases, EBUS revealed a poorly defined bronchial wall structure with two patterns of cartilaginous damage: fragmentation and edema. These cases were successfully treated by the implantation of nitinol stents, the sizes of which were determined by EBUS. EBUS was found to be useful in the diagnosis and treatment of RP.

Gefitinib as a first line of therapy in non-small cell lung cancer with brain metastases.

Two Japanese women were diagnosed as having well-differentiated adenocarcinoma of the lung with brain metastases. Since it was considered they could not tolerate conventional chemotherapy, we administered gefitinib without any previous systemic therapy. In both patients gefitinib acted dramatically on all the lesions including the brain metastases, resulting in a marked decrease of the elevated CEA levels, and improvement of their quality of life. Retrospective evaluation of epidermal growth factor receptor expression levels by immunohistochemistry revealed positive results in both cases. Though gefitinib has been recommended for patients previously treated with chemotherapy, it should be considered feasible as a first line therapy.

IgG4-related pleural disease presenting as a massive bilateral effusion.

A 74-year-old woman with massive bilateral pleural effusion, which was exudative in nature, and with mononuclear cell predominance underwent a pleuroscopy. Parietal pleura were thickened and partly reddish in color. Biopsy specimens taken from the parietal pleura revealed lymphoplasmacytic inflammation with fibrosis. As her performance status rapidly worsened with thoracentesis, we performed bilateral pleurodesis using talc. Pathologic evaluation of the pleural biopsy specimen with immunohistochemical staining revealed 91 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of 91%. Thus, the diagnosis of pleuritis from IgG4-related disease was established. Our case suggests that IgG4-related disease is one of the causes of pleural effusion, and it should be included in the differential diagnosis of unexplained pleuritis.

Talc pleurodesis for the management of malignant pleural effusions in Japan.

OBJECTIVE: Malignant pleural effusions are commonly treated with tube drainage followed by chemical pleurodesis to maintain the patient's quality of life. While talc is now accepted to be a worldwide gold-standard sclerosing agent for treating malignant pleural effusion, it is not yet approved in Japan. Instead, many patients are administered OK-432 for pleurodesis, which carries the risk of complications such as high-grade fever, chest pain, anaphylactic shock, interstitial pneumonia and acute renal failure. To assess the efficacy and safety of talc as a sclerosing agent in the management of malignant pleural effusions in Japanese patients. METHODS: Pleurodesis was performed using 4 g of sterile talc with thoracoscopic talc poudrage or the administration of talc slurry via a chest tube in patients with malignant pleural effusions. RESULTS: A total of 57 patients were included. The success rate of pleurodesis assessed on chest radiography at 30, 90 and 180 days was 90.6%, 80.9% and 76.1%, respectively. Complications occurring after talc pleurodesis included fever in 10.5% of the patients and chest pain in 14.0% of the patients. No major complications were reported. CONCLUSION: Talc pleurodesis is an effective and safe treatment for the management of malignant pleural effusion in Japanese patients.

New technique for endobronchial ultrasound-guided transbronchial needle aspiration to improve diagnostic yield.

BACKGROUND: Although the pooled sensitivity of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) using a convex scanning ultrasound bronchoscope is equivalent to the gold standard of mediastinoscopy, diagnosis cannot be obtained in a small number of patients with poor cellularity. The method described was investigated with the aim of avoiding puncturing the cartilage and enabling reliable tissue harvesting, as this can be expected to improve diagnostic yield. METHODS: Outer sheath method (OSM): While pressing the outer sheath (OS) of the puncture needle gently against the bronchial wall, the hyperechoic line appeared on surface of the bronchial wall on EBUS image. Then pulling and pushing the entire bronchoscope, the tip of OS moved to the epithelium above the bronchial cartilage while detecting the best position for puncturing on the EBUS images simultaneously. The bronchoscopist could visualize the cartilage moving longitudinally on EBUS image. The movement of the cartilage was stopped when the tip of the OS was caught in a concavity between 2 rings of cartilage. Group A consisted of 169 patients who underwent EBUS-TBNA before the introduction of OSM, and group B consisted of 169 patients who underwent EBUS-TBNA after the introduction of OSM. These 2 groups were compared with to investigate the usefulness of OSM. RESULTS: Adding this operation enabled a suitable puncture site to be identified, significantly improving diagnostic yield from 92.7% (group A) to 98.2% (group B). CONCLUSIONS: This method was regarded as useful for improving diagnostic yield by enabling the selection of a puncture site between rings of cartilage during EBUS-TBNA.

Novel approach for talc pleurodesis by dedicated catheter through flexi-rigid thoracoscope under local anesthesia.

For pleurodesis, talc administered by poudrage is usually insufflated blindly from a single port of entry using the standard method with a small-diameter rigid thoracoscope. In order to visually perform talc poudrage from a single port, we introduced a catheter technique through a flexi-rigid thoracoscope. Patients with uncontrolled and symptomatic pleural effusion requiring pleurodesis underwent flexi-rigid thoracoscopy under local anesthesia for talc poudrage. A dedicated catheter with 2.1-mm inner diameter was connected to a talc atomizer and inserted through the working channel of the flexi-rigid thoracoscope to insufflate talc into the pleural cavity under visualization. Nine patients were included in this study. Three patients were >75 years old, and two were Karnofsky performance status 50. Three patients received propofol for sedation and six were not sedated. Mean operative time was 30.8 min for all patients, and 21.3 min for cases without sedation. All procedures were performed easily under clear visualization with no major complications or catheter obstructions. This novel approach for talc pleurodesis using a catheter was well-tolerated and seems feasible for patients with uncontrolled pleural effusion. We consider this technique useful even for difficult cases, such as elderly patients or those with relatively low performance status.

Endobronchial ultrasonography and magnetic resonance imaging in tracheobronchial stenosis from ulcerative colitis.

A 49-year-old woman presented with continuous cough, progressive dyspnea on exertion, and hoarseness. She had a total colectomy for ulcerative colitis 17 years earlier. Bronchoscopy showed circumferential mucosal erythema. The surface of the tracheal mucosa was irregular and bled easily on contact. Endobronchial ultrasonography and magnetic resonance imaging (MRI) showed characteristic findings that suggested that the lesion was located within the tracheal mucosa and submucosa. Endobronchial ultrasonography images showed circumferential thickening of the mucosa, but tracheobronchial cartilage was preserved intact. Moreover, the comparison between tracheal tissues from tracheostomy and colon tissues resected 17 years earlier showed similarities in pathologic findings. These findings suggested that inflammatory bowel disease can cause the tracheobronchial stenosis.

Combination of chronic exercise and antihypertensive therapy enhances renoprotective effects in rats with renal ablation.

BACKGROUND: We assessed the renal protective effects of treatment with moderate exercise (EX), with EX plus olmesartan (OLS), with EX plus azelnidipine (AZN), and with the three together in a rat model of chronic renal failure (CRF). METHODS: Male 5/6-nephrectomized Wistar Kyoto (WKY) rats were divided into six groups according to the following treatments for: (i) no EX (C); (ii) moderate EX with treadmill running (20 m/min for 60 min/day, 5 days/week) (EX); (iii) EX+OLS (10 mg/kg/day); (iv) EX+AZN (3 mg/kg/day); (v) EX+OLS (5 mg/kg/day)+AZN (1.5 mg/kg/day); and (vi) sham operation (S). The rats were then treated for 12 weeks. RESULTS: EX, EX+OLS, EX+AZN, and EX+OLS+AZN showed decreases in the serum creatinine (Scr), an index of glomerular sclerosis (IGS), the relative interstitial volume of the renal cortex (RIV), the number of ED-1 (monoclonal antibody) positive cells (ED1(+)) and the glomerular expression score of alpha-smooth muscle actin (alpha-SMA(+)). EX+OLS, EX+AZN, and EX+OLS+AZN blocked the development of hypertension, increased the number of Wilms' tumor-1 (WT-1) positive cells (WT1(+)); EX+OLS and EX+OLS+AZN blunted the increases in proteinuria. In particular, blood urea nitrogen (BUN), ED1(+), alpha-SMA(+), WT1(+), IGS, and RIV in the EX+OLS+AZN were the lowest among all the nephrectomized groups. CONCLUSIONS: In the results, simultaneous treatment of EX, OLS, and AZN showed renal protective effects in this rat model suggesting that the treatment may affect the macrophage infiltration to the glomerulus, the fibroblast accumulation in the glomerulus, the mesangial activation, and the podocyte differentiation.

Intrapleural cisplatin and OK432 therapy for malignant pleural effusion caused by non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy of combined intrapleural therapy with cisplatin, an antineoplastic agent, and OK432, a sclerosing agent, in controlling malignant pleural effusions, when compared with monotherapy with either agent. METHODS: A total of 49 non-small cell lung cancer patients with malignant pleural effusion were randomly assigned to one of three groups: intrapleural cisplatin therapy (n = 17), intrapleural OK432 therapy (n = 17), or both (n = 15). They were compared in terms of success rate, duration of indwelling chest tube and adverse reactions. RESULTS: Rates of pleural effusion recurrence within 180 days following cisplatin, OK432, or combination therapy were 64.7%, 52.9% and 13.3%, respectively, being significantly lower in the combination therapy group (P = 0.01). The mean duration of chest tube drainage was 8.4 days, 5.5 days and 12.9 days, respectively, being significantly longer in the combination therapy group (P < 0.001). All procedures were well tolerated. CONCLUSIONS: Although chest tube drainage took longer because of the time required for multiple administration of the agents, intrapleural combination therapy with cisplatin and OK432 was more effective in controlling malignant pleural effusions due to non-small cell lung cancer than monotherapy with either agent.