picibanil and Pleural-Effusion

The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. On the 12th day after pleurodesis diffuse infiltrative shadows in the right lung, and frosted shadows in both lungs, were observed, and she was diagnosed with drug-induced lung injury. About 3 weeks after administration of prednisolone 1 mg/ kg a tendency for improvement in lung injury was observed, but the patient died of breast cancer progression. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature.

Topics: Adult; Breast Neoplasms; Female; Humans; Lung Diseases, Interstitial; Lung Injury; Picibanil; Pleural Effusion; Pleural Effusion, Malignant; Pleurodesis

To assess the use and efficacy of in-utero pleurodesis for experimental treatment of bilateral fetal chylothorax.. This was a study of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan between 2005 and 2009. Fetuses were karyotyped following amniocentesis and the lymphocyte ratio in the pleural effusion was determined following thoracocentesis. Forty-nine (62.8%) fetuses had a normal karyotype and were recognized to have fetal chylothorax; of these, 45 underwent intrapleural injection of 0.1KE OK-432 per side per treatment. We evaluated clinical (hydrops vs. no hydrops) and genetic (mutations in the reported lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as treatment outcome. Long-term survival was defined as survival to 1 year of age.. The overall long-term survival rate (LSR) was 35.6% (16/45); the LSR for non-hydropic fetuses was 66.7% (12/18) and for hydropic fetuses it was 14.8% (4/27). If we included only fetuses with onset of the condition in the second trimester, excluding those with onset in the third trimester, the LSR decreased to 29.4% (10/34). Notably, 29.6% (8/27) of hydropic fetuses had mutations in three of the four loci examined.. OK-432 pleurodesis appeared to be an experimental alternative to the gold-standard technique of thoracoamniotic shunting in non-hydropic fetal chylothorax. In hydropic fetuses, pleurodesis appeared less effective.

Topics: Amniocentesis; Chylothorax; Female; Fetal Diseases; Humans; Hydrops Fetalis; Karyotyping; Picibanil; Pleural Effusion; Pleurodesis; Pregnancy; Prognosis; Survival Rate; Taiwan; Ultrasonography, Prenatal

A 20-year-old woman, with systemic lupus erythmatosus complicated by steroid-and immunosuppressant-resistant bilateral pleural effusion, was admitted to the emergency room because of dyspnea and fever. Chest Xray film revealed bilateral massive pleural effusion. Bilateral thoracocentesis yielded fluid with chyle. Conservative treatment including intravenous hyper-alimentation and continuous drainage were performed but with no remarkable improvement. She underwent thoracoscopy-aided ligation of the thoracic duct. After the operation, bilateral pleurodesis was performed by intrathoracic injection of OK-432, because of uncontrolled pleural effusion. There have been no signs of recurrence at 10 months in this case of SLE with steroid-and immunosuppressant-resistant pleural effusion.

Topics: Adult; Chylothorax; Drainage; Drug Resistance; Female; Humans; Immunosuppressive Agents; Ligation; Lupus Erythematosus, Systemic; Picibanil; Pleural Effusion; Pleurodesis; Prednisolone; Thoracic Duct; Thoracoscopy; Treatment Outcome

In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in effusion lymphocytes from the other patients. Taken together, it is suggested that locoregional administration of OK-432 plus IL-2 is highly effective for the management of malignant effusion from colorectal cancer. OK-432 plus IL-2 induces autologous tumour-reactive CD4+ Th1 killer lymphocytes, which recognise tumour antigen(s) presented with HLA class II molecules on effusion tumour cells by means of preferential usage of TCRVbeta20. The clonotypic PCR using the TCRVbeta20-CDR3 sequences may be inf

Topics: Adult; Aged; Ascites; CD4-Positive T-Lymphocytes; Colorectal Neoplasms; Female; Humans; Immunotherapy; Interleukin-2; Lymphocyte Activation; Male; Middle Aged; Paracentesis; Picibanil; Pleural Effusion; Reverse Transcriptase Polymerase Chain Reaction

A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK-432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunity, Cellular; Lung Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Staging; Picibanil; Pleural Effusion; Prospective Studies; Tissue Adhesions

Sixty-seven breast cancer patients with malignant pleural effusions underwent their first thoracentesis between 1980 and 1990 at 13 institutes in Kyoto and Shiga Prefectures. They received various intracavitary treatments including OK-432 and cultured effusion lymphocytes (n = 29, group A), OK-432 alone (n = 12), chemotherapeutic agents alone (n = 9), OK-432 and chemotherapy (n = 16) or other (n = 1, lentinan and tetracycline) therapy. Response rate and median survival time were 90%, 12 months for group A, respectively and 40% and 3 months for other treatments (group B, n = 38), resulting in significant differences. Multivariate analysis using Cox's proportional hazard model showed that the immunotherapy using cultured lymphocytes was the most important factor prolonging survival among several significant prognostic factors such as concomitant liver metastasis, disease-free period and laterality of effusion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Cytarabine; Doxorubicin; Drainage; Female; Humans; Immunotherapy, Adoptive; Lymphatic Metastasis; Lymphocytes, Tumor-Infiltrating; Middle Aged; Mitomycin; Multivariate Analysis; Picibanil; Pleural Effusion; Prognosis; Proportional Hazards Models; Retrospective Studies; Survival Rate

Pleural effusion is a common complication in patients with malignant neoplasm. A randomized controlled study of intrapleural instillation of Adriamycin (control group, 30 patients) and Adriamycin Nocardia rubra cell wall skeleton (N-CWS group, 26 patients) with tube thoracostomy was performed in 55 patients with malignant pleural effusion due to primary lung cancer. The response rates for control of pleural effusion were 73.4% in the N-CWS group and 46.1% in the N-CWS group. These results suggest that intrapleural instillation using a combination of anti-cancer agent and immunopotentiator is an effective treatment for malignant pleurisy. Cardiac tamponade secondary to cancer is a life-threatening complication requiring immediate treatment. Twenty-four patients with malignant pericardial effusion were treated by intrapericardial instillation of anti-cancer drugs, such as Carbazilquinone, Mitomycin-C or ACNU, with pericardial drainage. The range of survival time from the instillation of anti-cancer drug was 3-365 days (average days). In only 4 patients, reaccumulation of pericardial effusion was recognized. There were no serious complications with this procedure. It was considered that local instillation of anti-cancer agents with pericardial drainage was a useful therapeutic modality for malignant pericarditis.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Bleomycin; Carcinoma, Squamous Cell; Cell Wall; Doxorubicin; Drainage; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Nimustine; Nitrosourea Compounds; Nocardia; Pericardial Effusion; Picibanil; Pleural Effusion; Random Allocation

Talc pleurodesis is commonly performed to manage refractory pleural effusion or pneumothorax. It is considered as a safe procedure as long as a limited amount of large particle size talc is used. However, acute respiratory distress syndrome (ARDS) is a rare but serious complication after talc pleurodesis. We sought to determine the risk factors for the development of ARDS after pleurodesis using a limited amount of large particle size talc.. We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital.. Twenty-seven and 35 patients underwent chemical pleurodesis using large particle size talc (4 g or less) or OK-432, respectively. Four of 27 (15%) patients developed ARDS after talc pleurodesis. Patients who developed ARDS were significantly older than those who did not (median 80 vs 66 years, P = 0.02) and had a higher prevalence of underlying interstitial abnormalities on chest computed tomography (CT; 2/4 vs 1/23, P < 0.05). No patient developed ARDS after pleurodesis with OK-432. This is the first case series of ARDS after pleurodesis using a limited amount of large particle size talc.. Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Female; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Particle Size; Picibanil; Pleural Effusion; Pleurodesis; Pneumothorax; Respiratory Distress Syndrome; Retrospective Studies; Risk Factors; Talc; Tomography, X-Ray Computed

Postoperative chylothorax is a rare but well-known complication of general thoracic surgery. Medical treatment of chylothorax was reported in the past, but there is still considerable controversy on the appropriate management strategies.Two patients with esophageal cancer underwent esophagectomy, 2-field lymph node dissection, and resection of thoracic duct together with ileocolic reconstruction via the retrosternal route at our hospital. Chylothorax developed on the 32nd postoperative day (POD) in 1 patient and the 12th POD in the other, manifesting as a change in the character of thoracic drainage to turbid white. Both were immediately started on octreotide (300 μg/ day) and etilefrine (120 mg/day). When the amount of pleural effusion decreased to <50 mL/day, we performed pleurodesis with Picibanil (OK432). Thereafter, the patients gradually made satisfactory progress and resumed oral food intake, and the thoracotomy tubes were eventually removed. They have remained recurrence-free at the time of writing.In this report, we demonstrated the clinical efficacy of etilefrine for the management of postesophagectomy chylothorax. New medical treatment options for this condition are now broad and the usefulness of combined therapy consisting of a sclerosing agent, etilefrine, and octreotide is underscored, regardless of the status of the thoracic duct.

Topics: Adult; Antineoplastic Agents; Chylothorax; Drug Therapy, Combination; Esophageal Neoplasms; Esophagectomy; Etilefrine; Humans; Male; Middle Aged; Octreotide; Picibanil; Pleural Effusion; Pleurodesis

In patients with refractory pleural effusion or pneumothorax, fever and elevated level of white blood cell count (WBC) are frequently observed after chemical pleurodesis with intrapleural injection of OK-432, which make it difficult to differentiate whether it was from the side effects of OK-432 or concurrent bacterial infection.. Procalcitonin (PCT) levels were measured before and after pleurodesis so as to discuss whether PCT is useful for distinguishing between the side effects of OK-432 and concurrent bacterial infection.. Twenty-six patients with refractory pleural effusion or pneumothorax who underwent chemical pleurodesis with intrapleural injection of OK-432 at the First Affiliated Hospital of Sun Yat-sen University between August 2010 and August 2012 were included in our study. Levels of PCT and WBC were measured before and after pleurodesis.. Of all 26 patients, 22 patients were with refractory pleural effusion, and the other four were with pneumothorax. The median serum levels of PCT and WBC elevated from 0.155 to 1.470 ng/mL (P = 0.009) and from 5.920 to 10.475 × 10(9) /L (P = 0.000), respectively. No patient was given antibiotics and fever subsided.. Intrapleural injection of OK-432 could increase the serum level of PCT and WBC with no bacterial infection. The serum PCT level may not be useful to distinguish whether fever was caused by the side effects of OK-432 or concurrent bacterial infection.

Topics: Adult; Aged; Antineoplastic Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Comorbidity; Female; Humans; Male; Middle Aged; Picibanil; Pleural Effusion; Pleurodesis; Pneumothorax; Protein Precursors; Young Adult

Chylothorax results from various causes, such as malignancy, trauma, or infection. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a multisystemic syndrome that is associated with plasma cell disorder. Pleural effusion is a common manifestation of POEMS syndrome, but the association of POEMS syndrome with chylothorax has not been reported. We report on a 61-year-old female patient who initially presented with dyspnea and bilateral leg edema. Importantly, the patient had normal renal function. Her chest X-ray and computed tomographic imaging showed bilateral pleural effusion, and her chest drainage revealed chylothorax. Detailed examination failed to reveal the definitive cause of the chylothorax. She received several treatments for chylothorax, namely, a low-fat diet or fasting, total parenteral nutrition, a somatostatin analog (octreotide), thoracic duct ligation by video-assisted thoracic surgery, and pleurodesis. However, further examination revealed endocrinopathy, monoclonal plasma cell disorder, peripheral neuropathy, and elevation of the serum level of vascular endothelial growth factor. The patient's condition was consequently diagnosed as POEMS syndrome. Eventually, her chylothorax was controlled by pleurodesis, and she was transferred to another hospital for stem cell transplantation. Herein, we report on the apparent first case of POEMS syndrome with chylothorax. In some cases of idiopathic chylothorax, the underlying primary disease may be latent, such as in the present patient. POEMS syndrome is rare, but this syndrome should be included in the differential diagnosis of chylothorax with unexplained etiology.

Topics: Chylothorax; Diagnosis, Differential; Dyspnea; Edema; Female; Humans; L-Lactate Dehydrogenase; Leg; Middle Aged; Picibanil; Pleural Effusion; POEMS Syndrome; Thoracic Surgery, Video-Assisted; Treatment Outcome; Triglycerides

Chylothorax is a relatively rare complication of thoracic surgery. Most instances of chylothorax after pulmonary resection are diagnosed within 3 days after surgery. Hence, late-onset chylothorax is rare. A 68-year-old woman underwent right lower lobectomy and mediastinal dissection for lung cancer. After discharge, the patient developed a dry cough, and chest radiography more than 3 months after surgery revealed a right-sided pleural effusion occupying more than half of the right hemithorax, which we diagnosed as late-onset chylothorax. Treatment comprised chest drainage, subcutaneous octreotide, and pleurodesis by injecting a preparation of OK-432. Follow-up chest radiography confirmed no reaccumulation of fluid. Three months later no recurrence of pleural effusion was detected. We report a rare case of postoperative late-onset chylothorax that proved difficult to treat.

Topics: Aged; Chest Tubes; Chylothorax; Combined Modality Therapy; Drainage; Female; Humans; Lung Neoplasms; Octreotide; Parenteral Nutrition, Total; Picibanil; Pleural Effusion; Pleurodesis; Pneumonectomy; Time Factors; Treatment Outcome

Hepatic hydrothorax in the absence of ascites is a rare complication of liver cirrhosis. A 71-year-old man with liver cirrhosis due to alcohol abuse was referred to our department because of massive pleural effusion on the right side. The properties of pleural effusion and clinical course led to a diagnosis of hepatic hydrothorax. Nonsurgical OK-432 pleurodesis resulted in a marked decrease of pleural effusion. After 2 months of follow-up, effusion was well-controlled. Patients with hepatic hydrothoraces have few options. OK-432 pleurodesis is relatively safe and may provide an effective alternative to peritoneovenous shunt, transjugular intrahepatic portosystemic shunt or surgical pleurodesis. It may also be a bridge toward liver transplantation in patients with few other options. Herein, we report a case of refractory hepatic hydrothorax successfully treated by nonsurgical OK-432 pleurodesis.

Topics: Aged; Drainage; Humans; Hydrothorax; Liver Cirrhosis, Alcoholic; Male; Picibanil; Pleural Effusion; Pleurodesis; Radiography; Treatment Outcome

We report a case of secondary amyloidosis with pleural involvement in a patient with rheumatoid arthritis. A 77-year-old man had received a diagnosis of rheumatoid arthritis 10 years previously. Bilateral pleural effusion of unknown etiology was noted 2 years prior to admission. A biopsy of the left pleura by video-assisted thoracic surgery did not reveal any evidence of the cause of his pleural effusion. The histological findings revealed chronic inflammation of the pleura on a hematoxylin-eosin (HE) stain, but treatment with an increased dose of corticosteroid did not improve his effusion. Right pneumothorax then developed. Based on the histological findings of a Congo red stain, the diagnosis was changed to pleural amyloidosis. An initial attempt at pleurodesis with OK-432 and a pleural patch with the patient's own blood was attempted but was not successful. Subsequently, pleurodesis with OK-432 and the patient's own blood improved his pleural effusion and pneumothorax. Pleural involvement in amyloidosis is extremely rare and is difficult to treat.

Topics: Aged; Amyloidosis; Arthritis, Rheumatoid; Blood; Humans; Male; Picibanil; Pleural Diseases; Pleural Effusion; Pleurodesis

OK-432 therapy is effective for the treatment of macrocystic lymphatic malformations (LMs), but the optimal management of patients with microcystic LMs associated with large chylous pleural effusions or chylous ascites is not resolved. We performed thoracoscopic- or laparoscopic-guided injection of OK-432 for 2 patients with diffuse microcystic LMs accompanied by refractory chylous pleural effusion or chylous ascites. Both cases responded well to OK-432 therapy with improvement/resolution of fluid collections and associated symptoms. We recommend the use of OK-432 therapy as a promising treatment for microcystic LMs with functionally significant lymphatic fluid collections.

Topics: Adult; Chylothorax; Chylous Ascites; Female; Humans; Infant, Newborn; Injections; Lymphatic Abnormalities; Picibanil; Pleural Effusion; Sclerosing Solutions

Chylothorax is a relatively uncommon condition defined as an abnormal collection of lymphatic fluid within the pleural space. We are reporting the use of OK-432 for treatment of prolonged idiopathic congenital chylothorax in 2 newborn infants who failed to respond to conservative medical therapy, including octreotide injection.

Topics: Antineoplastic Agents; C-Reactive Protein; Chest Tubes; Chylothorax; Female; Humans; Infant, Newborn; Instillation, Drug; Male; Octreotide; Picibanil; Pleural Effusion; Respiration, Artificial; Treatment Failure

A 60-year-old woman had received adjuvant chemotherapy after abdominal hysterectomy for clear cell carcinoma of the endometrium. She had no history of allergy. She was admitted to our hospital because of massive pleural effusion. She underwent drainage of left-side malignant pleural effusion followed by chemical pleurodesis with OK-432 via a chest tube. Ten minutes after administration of OK-432 to the thoracic cavity, she complained of dyspnea and showed general flushing. Since the clinical course suggested drug-induced anaphylactic reaction, she was immediately treated with an adrenaline subcutaneous injection and methylprednisolone sodium succinate intravenous injection. However, the respiratory insufficiency progressively deteriorated and mechanical ventilation was needed for the next 3 days. This is the first published case of anaphylactic reaction to OK-432 pleurodesis. In Japan, OK-432 is a key drug used for pleurodesis and we should consider possible serious adverse reactions include anaphylactic reaction.

Topics: Anaphylaxis; Female; Humans; Middle Aged; Picibanil; Pleural Effusion; Pleurodesis

Topics: Aged; Female; Humans; Liver Cirrhosis; Picibanil; Pleural Effusion; Pleurodesis

A 70-year-old female presented with yellow discoloration of the nail beds of all fingers and toes, as well as bilateral pleural effusions. The patient was diagnosed as having the yellow nail syndrome based on the triad of yellow nails, lymphedema, and pleural effusions. The patient's intractable bilateral pleural effusion was treated with pleurodesis using OK-432. The treatment prevented the accumulation of pleural fluid for a long period of time. Pleural effusion associated with yellow nail syndrome is thought to be difficult to treat; however, this patient's excellent clinical course suggests that pleurodesis with OK-432 could be used to treat the disease in the future.

Topics: Aged; Antineoplastic Agents; Female; Humans; Lymphedema; Nail Diseases; Picibanil; Pigmentation Disorders; Pleural Effusion; Pleurodesis; Syndrome; Treatment Outcome

The treatment of massive osteolysis with lymphangioma and/or hemangioma (Gorham-Stout syndrome) has been controversial. The authors report on a patient with multiple massive osteolyses and extensive lymph-hemangiomatosis whose lesions were reduced by interferon alfa therapy. A 2-year-old girl had complained of left chylothorax. Thoracoscopy showed an increase in small lymphatic vessels in the chest wall. The chylothorax was improved by coagulation of the lymphatic vessels. Later, multiple massive osteolyses appeared in the left 11th and 12th ribs, the TH10-L3 vertebrae, and the right femur. There were also hemangiomas in the liver and spleen, a tumor lesion in the left lower chest wall, and hemangiomatous change on the skin surface of the left back. The left lung had only a minimal air content. After OK-432 was injected into the femur and chest wall lesions, the femur lesion disappeared. Then, as right chylothorax appeared, OK-432 was injected into the right pulmonary cavity. The chylothorax disappeared, but pericardial effusion appeared. After steroid pulse therapy, pericardial effusion disappeared. During these treatments, the 7th to 10th ribs disappeared from the x-ray and scoliosis developed. One month later, a cloudy fluid collection in the right lung was found on computed tomography. Interferon alfa and steroid pulse therapy were started. Interferon alfa (1,500,000 units) was subcutaneously administered daily for 2 months and was gradually reduced and maintained at 1,500,000 unit/wk. Steroids were also reduced and maintained at 5 mg/d of predonine. Later, the progress of osteolysis and the extension of lymph-hemangiomatosis stopped. Ten months later, hemangioma in the back disappeared, and the 7th to 10th ribs, which had disappeared, reappeared. The interferon alfa therapy was stopped 14 months after it was administered. The patient's condition has been stable for 10 months since then. At this time, computed tomography shows regression of the hemangiomatous lesion in the back. The authors clinically diagnosed the patient as having Gorham-Stout syndrome with extension of lymph-hemangiomatosis. Interferon alfa with or without steroid therapy should be a choice for patients with extension lesions.

Topics: Adrenal Cortex Hormones; Angiogenesis Inhibitors; Antineoplastic Agents; Child, Preschool; Chylothorax; Drug Therapy, Combination; Female; Femur; Hemangioma; Humans; Interferon-alpha; Liver Neoplasms; Lymphangioma; Neoplasms, Multiple Primary; Osteolysis, Essential; Picibanil; Pleural Effusion; Pulmonary Atelectasis; Remission Induction; Ribs; Scoliosis; Skin Neoplasms; Spine; Splenic Neoplasms; Syndrome; Thoracic Neoplasms

A 38-year-old multiparous woman was referred at 19 weeks' gestation because of hydrops fetalis. Ultrasonic examination revealed severe pleural effusion, ascites and skin edema. Detailed examination of the amniotic fluid, fetal blood and intrathoracic fluid led to a diagnosis of congenital fetal chylothorax. Repeated thoracocenteses were not effective in improving the hydrops fetalis. We introduced fetal treatment for the pleural effusion by an intrapleural injection of OK-432 at 23, 24 and 25 weeks' gestation. The pleural effusion was reduced by adhesion of the intrathoracic space and resulted in the delivery of a neonate who was healthy except for right renal dysfunction. Pulmonary hypoplasia was successfully prevented by OK-432.

Topics: Adult; Antineoplastic Agents; Chylothorax; Female; Fetal Diseases; Humans; Injections, Intralesional; Picibanil; Pleural Effusion; Pleurodesis; Pregnancy; Ultrasonography, Prenatal

We present a case of pleurodesis by intrapleural injection of OK-432 for the treatment of fetal chylothorax at an early gestational age. OK-432 injection achieved rapid and effective control of pleural effusion with no adverse effects.

Topics: Adult; Antineoplastic Agents; Chylothorax; Female; Fetal Diseases; Humans; Picibanil; Pleural Effusion; Pleurodesis; Ultrasonography, Prenatal

A 67-year-old female patient with biopsy proven AL systemic amyloidosis developed rapidly progressive dyspnea. Chest roentgenogram and CT scan revealed a large right pleural effusion in addition to nodular lesions with bilateral hilar lymphadenopathy. The patient's serum showed IgG lambda type monoclonal gammopathy and she also had Bence Jones proteinuria. The pleural effusion was an exudate that contained many mononuclear cells and a high concentration of protein. Cardiac function was not seriously disturbed. Except for amyloidosis, no other causes for the severe pleural effusion were found. This patient was treated with chemical pleurodesis using Picibanil and a low dose of prednisolone. Eighteen months after this treatment, her right pleural effusion did not recur. Bronchopulmonary tissues are known to be frequently involved by AL systemic amyloidosis, but a nodular pattern of pulmonary amyloid deposition and a unilateral large pleural effusion are rare clinical manifestations in this disease.

Topics: Aged; Amyloid; Amyloidosis; Female; Histocytochemistry; Humans; Lung Diseases; Picibanil; Pleural Effusion; Prednisolone; Radiography

The effect of intrapleural injection of OK-432, a streptococcal preparation, for management of carcinomatous pleural effusion was investigated in patients with non-small cell lung cancer (NSCLC). Ten patients, including 5 men and 5 women with performance status 2-3(ECOG) and average age of 66.4 years, received OK-432 for different times after the tumor burden in effusion was relieved with adequate drainage. The response rate was 100% in terms of decreased reaccumulation of pleural fluid, improvement of general status, and disappearance of tumor cells in the fluid. The adverse effects of this treatment were mild-including fever, chills, chest pain and nausea-and all were tolerable to patients. Median survival time was 4.5 months after treatment. This preliminary report indicates that intrapleural injection of OK-432 is an effective alternate method for management of carcinomatous pleural effusion to improve the quality of life for terminally ill cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion; Time Factors

Sixty-seven breast cancer patients with cytologically-confirmed malignant pleural effusion, who required intrapleural treatment, were analyzed retrospectively. The patients received their first thoracentesis between 1980 and 1990. Among them, 29 patients received intrapleural administration of OK-432, a streptococcal preparation, followed by the transfer of autologous pleural effusion lymphocytes cultured with interleukin-2. Other intrapleural treatments consisted of OK-432 alone (12 patients), chemotherapeutic agents alone (n = 9), a combination of OK-432 and chemotherapy (n = 16), or others (n = 1). Twenty-six of the 29 patients given OK-432 plus cultured effusion lymphocytes responded, while only 15 of the 38 patients who received other treatments did (p < 0.01). Median survival time and 5-year survival rate of patients who received OK-432 and cultured lymphocytes was 12 months and 36%, while those of the patients who received other treatments was 3 months and 0%, a significant (p < 0.001) difference in survival. Multivariate analysis using Cox's proportional hazard model revealed that the treatment (adoptive immunotherapy) was the most significant (p < 0.005) factor to prolong the survival of the patients among several prognostic factors. Thus, OK-432 and adoptive immunotherapy is a promising therapy that should be further evaluated in a prospective study.

Topics: Adult; Aged; Breast Neoplasms; Combined Modality Therapy; Female; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Multivariate Analysis; Picibanil; Pleural Effusion; Prognosis; Retrospective Studies; Survival Rate

Intraperitoneal and pleural immunotherapy has been used as an effective therapy for malignancy. Recently we treated two patients with peritonitis and pleuritis due to cancer by intraperitoneal and pleural administration of IFN-gamma, OK-432 and antitumor agents. One patient with gastric cancer (stage IIIb) was treated with intraperitoneal administration of IFN-gamma and OK-432 in combination with intraarterial infusion of MMC, ADM, 5-FU and CDDP. Two months later, ascites and pleural fluid diminished. Another patient with ovarian carcinoma (stage IV), was administered IFN-gamma, OK-432 and CDDP into ascites with general medication of CDDP and Epi-ADM. Two months later, her ascites and tumor size decreased. This patient was treated with palaplatin every two months for the ten months and hysterosalpingecctomy and tumorectomy of Douglas pouch were performed at the sixteenth month. The histopathological examination of resection from this patient showed complete necrotic tissue of tumor. Endogenous cytokine therapy with intraperitoneal and pleural administration of IFN-gamma for priming and OK-432 for eliciting in combination with antitumor agents may be effective treatment for malignant peritonitis and pleuritis.

Topics: Adenocarcinoma, Mucinous; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Epirubicin; Female; Humans; Infusions, Intravenous; Infusions, Parenteral; Interferon-gamma; Male; Middle Aged; Ovarian Neoplasms; Peritonitis; Picibanil; Pleural Effusion; Pleurisy; Stomach Neoplasms

The therapeutic and immunomodulating potential of biological response modifiers (BRM) such as OK-432 (a streptococcal preparation) and recombinant interferon gamma (rIFN-gamma) has been evaluated in 15 patients with advanced chemotherapy resistant ovarian cancer, presenting malignant ascites and/or pleural effusions. OK-432 was injected intracavitary in 10 patients in increasing doses from 0.2 up to 7.5 mg weekly. Five women were treated intracavitary with rIFN-gamma twice a week. The initial dose was 0.1 mg/m2 which was raised up to 12 mg/m2 over 6 weeks. With OK-432 a complete response was achieved for 14.1 + 8.9 months in 4 patients, a partial response for 1.7 + 0.3 months in 3 patients. The survival time of the 4 responders was significantly longer (21.1 + 8.3 months) than the survival time of the patients with partial or no response (4.9 + 2.7,4.1 + 2.3 months, respectively). In the rIFN-gamma therapy group, we found a partial response in one and no response in 4 patients. Toxicity observed under OK-432 and rIFN-gamma was minimal in all patients, suggesting a lack of systemic effect of intracavitary-applied BRM. With both agents, augmentation of certain immune responses, especially in the peritoneal cavity and to a lesser extent in the peripheral blood, has been documented. In 5 patients treated with OK-432, we found an overall augmentation of the effusion macrophage killer activity. rIFN-gamma augmented natural killer activity in 2 of 3 patients.

Topics: Aged; Ascitic Fluid; Cytotoxicity, Immunologic; Female; Humans; Immunologic Factors; Injections, Intraperitoneal; Interferon-gamma; Killer Cells, Natural; Macrophages; Middle Aged; Ovarian Neoplasms; Picibanil; Pleural Effusion; Recombinant Proteins

Topics: Adenocarcinoma; Aged; Biological Products; Cell Cycle; Cytotoxicity, Immunologic; Female; Glycoproteins; Humans; Lung Neoplasms; Lymphoma; Male; Middle Aged; Picibanil; Pleural Effusion; Tumor Necrosis Factor-alpha

Topics: Aged; Aged, 80 and over; Biological Products; Female; Glycoproteins; Growth Inhibitors; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion; Pleurisy; Tumor Necrosis Factor-alpha

Ten patients with carcinomatous pleural effusions were treated with single intrapleural (i.pl.) injections of the streptococcal preparation OK432 on day 0 and the effects of i.pl. OK432 on the lysis of fresh or cryopreserved autologous tumor cells isolated from the pleural effusions were observed on day 7. In eight patients tumor cells in the effusions had decreased or disappeared by day 7. The other two patients, however, had no clinical evidence of therapeutic benefit from i.pl. OK432. Effusion tumor cells were relatively resistant to lysis by autologous lymphocytes when tested in a 4-h 51Cr-release assay. Positive reactions were recorded for blood and effusion lymphocytes in two of ten untreated patients. Injection of OK432 i.pl. resulted in an induction or augmentation of cytotoxicity against autologous tumor cells and K562 in the effusions of seven of ten subjects by day 7. In contrast, autologous tumor killing activity of blood lymphocytes was not always modified by i.pl. OK432. Purification of large granular lymphocytes (LGL) by discontinuous Percoll gradient centrifugation enriched autologous tumor killing activity, with no reactivity in LGL-depleted, small T lymphocytes. Significant lysis of autologous tumor cells was observed with effusion LGL from seven of ten untreated patients. Seven days after i.pl. OK432 injection, effusion LGL expressed enhanced cytotoxicity against autologous effusion tumor cells, whereas T cells were still not cytotoxic to autologous tumor cells on day 7. The frequency of LGL among effusion lymphocytes was not altered by i.pl. OK432. Adherent effusion cells were not involved in lysis of autologous effusion tumor cells in either untreated or OK432-treated patients. In vitro treatment of blood and effusion lymphocytes with OK432 induced an enhancement of autologous tumor-killing activity in patients who subsequently responded to i.pl. OK432 treatment. OK432 augmented in vitro autologous tumor killing activity of LGL, whereas T cells failed to lyse autologous tumor cells even after in vitro activation with OK432. These results indicate that i.pl. administration of OK432 to cancer patients will result in an augmentation of autologous tumor killing activity of LGL in the pleural effusions, and that this could be responsible for the antitumor activity of i.pl. OK432 therapy.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Carcinoma, Squamous Cell; Cell Adhesion; Cytotoxicity, Immunologic; Humans; Immunotherapy; Killer Cells, Natural; Lung Neoplasms; Middle Aged; Picibanil; Pleural Effusion; T-Lymphocytes

Twelve patients with carcinomatous pleural effusions were treated with single intrapleural (i.pl.) administration of OK432 on day 0 and the effects of i.pl. OK432 on natural killer (NK) cell activity were followed on day 7. Two patients showed no clinical evidence of therapeutic benefit from i.pl. OK432. In the other 10 patients, pleural effusions and/or tumor cells in the effusions had decreased or disappeared by day 7. NK cell activity was markedly low or absent in pleural effusions of untreated patients due to the presence of adherent effusion cells capable of suppressing the maintenance and interferon-induced augmentation of NK cell activity. I.pl. injection of OK432 resulted in enhancement of NK cell activity and abrogation of NK suppressor cell activity in the effusions. On the other hand, blood NK cell activity was not consistently altered by i.pl. OK432. In vitro treatment of effusion mononuclear cells from untreated patients with OK432, but not with interferon, augmented NK cell activity. In addition, adherent effusion cells of untreated patients lost their NK suppressor function following in vitro OK432 treatment. These results suggest that i.pl. administration of OK432 will result in augmentation of NK cell activity and reduction of NK suppressor cell activity in pleural effusions, which could be responsible for the antitumor activity of i.pl. OK432.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Carcinoma, Squamous Cell; Female; Humans; Interferon Type I; Killer Cells, Natural; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion; T-Lymphocytes, Regulatory

Pleural effusions and sera of two patients with lung cancer were tested after intrapleural injection of OK-432 as an anticancer drug for IFN-alpha activity by biological assay and for IFN-alpha as an antigen by radioimmunoassay. The titers by radioimmunoassay were fairly consistent with those by biological assay, but were usually higher. In Case 1, IFN-alpha was observed fairly early after administration of OK-432 and only in pleural effusions. In Case 2, induction of IFN-alpha at low level was observed late after the first administration of OK-432 both in the pleural effusion and serum and was detected only by radioimmunoassay.

Topics: Adenocarcinoma; Aged; Biological Products; Carcinoma, Small Cell; Drug Therapy, Combination; Female; Humans; Injections; Interferon Type I; Lung Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Pleura; Pleural Effusion

Lymphocytes from peripheral blood (PBL) and from pleural effusions (PEL) of cancer patients were tested for cytotoxicity against tumor cells freshly isolated from carcinomatous pleural effusion of the same patient. Significant lysis of autologous tumor cells was recorded for 4 of 28 PBL samples and for 5 of 28 PEL cases when investigated in a 4-hour 51Cr release assay. In vitro treatment of lymphocytes for 20 hours with the streptococcal preparation OK432 resulted in an induction or augmentation of cytotoxicity against autologous tumor cells in 21 of 28 PBL and PEL specimens. OK432-induced cytotoxicity required active cell metabolism, RNA and protein syntheses, but not DNA synthesis of lymphocytes. Supernatants of OK432-stimulated lymphocytes, and interferon and interleukin 2 failed to induce autologous tumor killing. Nylon wool-nonadherent lymphocytes were involved in both spontaneous and OK432-induced lysis of fresh autologous tumor cells. OK432-activated lymphocytes from normal donors and cancer patients caused lysis of fresh allogeneic tumor cells and also K562 cells.

Topics: Adenocarcinoma; Adult; Aged; Biological Products; Cytotoxicity, Immunologic; Dactinomycin; Female; Humans; Killer Cells, Natural; Leukemia; Lung Neoplasms; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Pleural Effusion