picibanil and Skin-Neoplasms

We performed a study of intralesional OK-432 injection therapy for the non-surgical treatment of ganglions. OK-432 is an agent made from penicillin-killed and lyophilized preparations of a low-virulence strain of group A streptococcus pyogenes, which has been developed as an immune-augmentation agent for cancer therapy. Derived from an extract of bacterial culture it, induces an immunological response and causes local inflammation and subsequent tissue shrinkage following intralesional injection. After skin anesthesia and aspiration of the ganglion contents, OK-432 was injected into the ganglion cavity. When the ganglion recurred, this procedure was repeated usually up to a total of three times. Clinical evaluations six months after the last injection were: 56.6% complete cure, 35.3% incomplete cure with size reduced, 7.5% no change. Complications were as follows. There were no cases of shock. High fever was seen in five patients (9.4%); two patients suffered a high fever up to 39.0 degrees C for one day, and the others had fevers from 1 to 3 days. Thirty-two patients (60.4%) complained of local swelling that persisted for 1 to 7 days, and 11 (20.8%) complained of continuous pain for 1 to 3 days. Intralesional OK-432 injection therapy is thought to be a safe and convenient alternative to surgical treatment.

Topics: Antineoplastic Agents; Female; Humans; Injections, Intralesional; Lymphangioma; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Skin Neoplasms; Treatment Outcome; Ultrasonography

Prognosis was obviously poor in PPSM-treated stage Ib cases, compared with extra PPSM-treated counterparts (P less than 0.01). Out of the PPSM-treated stage Ib cases, those where prophylactic lymph node dissection was performed ran a prognosis similar to the extra PPSM-treated stage Ib cases: it is advisable therefore to perform the prophylactic lymph node dissection actively in the PPSM-treated stage Ib cases. A response rate of 28.6% was achieved with PAV therapy in stage IV cases, with metastases to the skin, subcutaneous tissue, lymph nodes and bone responding to the therapy. PAV therapy, when applied in operable cases, brought about excellent 5-year survival rates as 100% high as in stage Ia, 92.9% in stage Ib, 53.1% in stage II, and 66.9% in stage Ib + II cases. In a randomized, controlled study of bestatin in stage Ib and II cases over about 4 years has revealed that both the disease-free rate and the survival rate were significantly high in the bestatin-treated group, compared with the control group.

Topics: Adult; Aged; Female; Humans; Leucine; Lymph Node Excision; Male; Melanoma; Middle Aged; Neoplasm Staging; Picibanil; Prognosis; Sex Factors; Skin Neoplasms

Topics: Aged; Antineoplastic Agents; Fatal Outcome; Hemangiosarcoma; Hemothorax; Humans; Male; Paclitaxel; Picibanil; Pleural Neoplasms; Pleurodesis; Pneumothorax; Recurrence; Skin Neoplasms

Topics: Aged; Anti-Infective Agents, Local; Antineoplastic Agents; Cytoreduction Surgical Procedures; Ethanol; Groin; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Melanoma; Pelvis; Picibanil; Skin Neoplasms

Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Humans; Injections, Intralesional; Interferon-gamma; Male; Picibanil; Skin Neoplasms; Tumor Burden; Tumor Necrosis Factor-alpha

Retiform hemangioendothelioma (RH) is a rare low-grade malignancy angiosarcoma, with a high rate of local recurrence and a low metastatic risk. A 6 year-old girl with a large cervical cystic lymphangioma diagnosed by ultrasound and Doppler ultrasound, which showed a large multiloculated anechoic cyst with no flow. The lymphangioma was treated with injections of Picibanil (OK-432). The tumor regressed, but after a year, she developed a poorly limited infiltrated plaque spreading out regularly over her chest, back, and shoulder. The biopsy showed a poorly limited dermal and subcutaneous vascular proliferation composed of elongated arborising vessels lined with ovoid endothelial cells in a hobnail pattern. In addition, the deep part of the lesion showed typical features of a papillary intralymphatic angioendothelioma pattern (PILA) or Dabska tumor. The endothelial cells strongly expressed podoplanin (D2-40). A diagnosis of RH with focal areas of PILA was reached. The girl died 8 months after surgery of hypovolemic shock in a context of diffuse lymphangiomatosis with pulmonary localization. To our knowledge, RH has hardly ever been described in children. This entity exhibits a continuum with the PILA, sharing not only morphological and immunohistochemical similarities but also its ability to develop in a context of a vascular anomaly, particularly a lymphangioma. The role of Picibanil in the development of this tumor can be discussed.

Topics: Antineoplastic Agents; Child; Female; Hemangioendothelioma; Humans; Lymphangioma, Cystic; Neoplasms, Second Primary; Picibanil; Skin Neoplasms

A 72-year-old man was referred to our hospital because of bilateral pleural effusion. Although examination of pleural effusion obtained by thoracentesis did not show any specific etiology, we diagnosed yellow nail syndrome due to his yellow nails and lymphedema of both lower limbs. Diuretics were effective for the control of his pleural effusion. Subsequently, fibrosarcoma was found in his abdominal skin and was resected. The pleural effusion gradually increased after the cessation of oral diuretics. Histological examination of a pleural biopsy specimen obtained by thoracoscopy showed chronic lymphocytic inflammation, but no malignancy. His previously intractable right pleural effusion was successfully treated with pleurodesis using OK-432, suggesting that pleurodesis with OK-432 could be an effective method for the control of pleural fluid in this disease.

Topics: Aged; Fibrosarcoma; Humans; Male; Picibanil; Pleurodesis; Skin Neoplasms; Yellow Nail Syndrome

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

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Interleukin-2; Picibanil; Recombination, Genetic; Scalp; Skin Neoplasms

An 80-year-old woman with angiosarcoma of the scalp was treated with radiation and interleukin 2. The patient experienced dyspnea one month later because of pulmonary metastases, and underwent video-assisted thoracoscopic surgery for a right pneumothorax. Right hemopneumothorax recurred 3 weeks after the surgery and left hemopneumothorax occurred 4 months later. Both were successfully treated with intrapleural OK432 and drainage. As of March 1995 the patient had been alive and well for one year since the right pneumothorax developed.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Female; Hemangiosarcoma; Hemopneumothorax; Humans; Lung Neoplasms; Picibanil; Pleura; Skin Neoplasms

Many drugs are applied in local treatment for skin malignant tumors. These drugs are living-BCG, OK-432, MY-1, WPG, interferon preparation (alpha, beta and gamma), TNF, IL-2, peplomycin, bleomycin and others. Some of them already have completed clinical trials and others are under clinical observation. In local administration of these drugs, skin lesions (malignant melanoma, CTL-mainly mycosis fungoides, carcinoma in situ and others) show good improvement. The effects were more observed in the tumors with diameters of 1 cm or less and appeared 3 to 10 injections in most cases. As complications, there are fever, general fatigue, vomiting, anorexia, leucopenia and others. Among them, the fever was most observed immediately after injections without any more severe complications. It may be concluded that treatment by intratumoral administration is useful for skin malignant tumors.

Topics: Aged; Antineoplastic Agents; BCG Vaccine; Drug Evaluation; Fever; Humans; Injections; Interferons; Male; Middle Aged; Picibanil; Skin Neoplasms

This paper introduces the current status of melanoma treatment with various biologic response modifiers (BRMs) in Japan, with an emphasis on the clinical results of Interferon therapies. The authors also refer briefly to the current situation of interleukin-2 (IL-2) and tumor necrosis factor (TNF) in Japan. Many BRMs have been used in treatment of melanoma, e.g., IFN, IL-2, TNFs, BCG, MY-1 (DNA extracted from BCG), WPG (CWs of Bifidobacterium infantis, ATCC 15697), OK-432 (Picibanil, Streptococcus pyogenes preparation), bestatin, and forphenicinol. Some of these have completed clinical trials, while others are still undergoing clinical testing. Among IFN-alpha, beta, and gamma, intralesional administration of natural IFN-beta was found to be more effective than IFN-alpha for metastatic skin melanoma, the survival time of patients being prolonged by the administration of IFN-beta. IFN-gamma appeared to have lower efficacy than IFN-alpha and beta. The frequency of BRM application to melanoma treatment will increase. The authors foresee that combinations with radio- and/or other chemotherapy will be more common than the single use of a BRM, especially in the case of IFN.

Topics: Biological Factors; Biological Products; Cell Wall Skeleton; Cytokines; DNA, Bacterial; Glycine; Humans; Interferon Type I; Interferon-gamma; Interferons; Interleukin-2; Leucine; Male; Melanoma; Middle Aged; Mucoproteins; Mycolic Acids; Picibanil; Recombinant Proteins; Skin Neoplasms; Tumor Necrosis Factor-alpha

Giant cavernous haemangioma was treated successfully with a new therapy consisting of intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin). Complete regression was observed within 3 months without serious side effects except for fever of 2-3 days' duration and local inflammatory reaction lasting for 3-4 days. Local inflammatory reaction did not cause any damage to the overlaying skin and did not lead to scar formation.

Topics: Biological Products; Dose-Response Relationship, Drug; Female; Hemangioma, Cavernous; Humans; Infant; Injections; Picibanil; Skin Neoplasms; Thoracic Neoplasms

The effect of treatment with bacterial preparations on blood flow in normal and malignant tissues was investigated, clinically and experimentally. The time course of the local effect of the preparations was recorded by Laser Doppler Velocimetry (LDV) via a probe on the surface of normal and malignant tissues directly over the injection site. Experimentally, no definite enhancement of blood flow with OK-432, a streptococcal preparation, was observed in nude mice. Clinically, intradermal administration of OK-432 or tuberculin (PPD) resulted in an approximate 11-or 4-fold increase in blood flow, respectively. The injection of OK-432 into malignant tissues, such as dermal cancer and breast cancer with direct extension to the skin, resulted in an approximate 3.5-fold increase. The results suggested that bacterial preparations can act as an adjuvant to enhance drug delivery to tumor tissue in cancer chemotherapy, and that the enhancement of blood supply is induced by immune response.

Topics: Adult; Aged; Animals; Biological Products; Blood Volume; Breast Neoplasms; Esophageal Neoplasms; Female; Humans; Lidocaine; Lung Neoplasms; Male; Mice; Mice, Nude; Microcirculation; Middle Aged; Picibanil; Regional Blood Flow; Skin; Skin Neoplasms

The application of a heat pad in the hyperthermia treatment of malignant skin tumors was examined. The temperature on the skin surface, and at a depth of 1 mm and 2 mm became 42C, 41C and 40C respectively, and was maintained for 4 hours. Two patients were treated with the heat pad alone, four were treated in combination with radiotherapy and one patient each with Pepleomycin injection and Bleomycin ointment. Irrespective of the above methods used, the heat pad was effective.

Topics: Adult; Aged; Bleomycin; Breast Neoplasms; Combined Modality Therapy; Female; Hot Temperature; Humans; Lung Neoplasms; Male; Middle Aged; Ointments; Peplomycin; Picibanil; Skin Neoplasms; Skin Temperature

Skin metastasis of malignant melanoma has been difficult to control by chemoimmunotherapy. We report a case of melanoma with marked reduction of multiple skin and lung metastasis and an improved cell-mediated immunity using combined DAV (DTIC, ACNU, Vincristine) and OK-432 chemoimmunotherapy in association with doses of indomethacin administered over a long period (250 mg/day, 6 months) to relieve the cancerous pain.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Humans; Indomethacin; Lung Neoplasms; Male; Melanoma; Nimustine; Nitrosourea Compounds; Pain, Intractable; Picibanil; Skin Neoplasms; Suppositories; Vincristine

This study, based on a cooperative group project involving 4 major medical institutes in Japan, presents the second survey of malignant melanoma patients (198 cases) where an attempt is made to systemically evaluate the survival rates of these patients with respect to the tumor thickness and location of primary lesions, and the response to chemoimmunotherapy. More than 50% of total collected cases showed the primary lesions on the limbs. The most common type and site of involvement is the acral lentiginous melanomas involving the plantar areas (more than 30). The survival rates affecting the limbs were better than those affecting the non-limb areas. However, the comparison of the survival rates did not reveal any difference between those cases affecting the plantar and non-plantar areas. The difference in the prognosis of melanoma patients appeared to be related to the tumor thickness. By historical comparison, the DAV (DTIC, ACNU, VCR) treated group exhibited a better survival rate than the non-DAV treated group. Furthermore, the DAV group with immunoadjuvant therapy (mainly OK-432) showed a better prognosis than the DAV group without any immunoadjuvant therapy.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Child; Dacarbazine; Female; Foot; Hand; Humans; Japan; Male; Melanoma; Middle Aged; Nimustine; Nitrosourea Compounds; Picibanil; Proteoglycans; Skin Neoplasms; Vincristine

Topics: BCG Vaccine; Cytotoxicity, Immunologic; Humans; Killer Cells, Natural; Phytohemagglutinins; Picibanil; Pokeweed Mitogens; Polysaccharides, Bacterial; Skin Neoplasms

Topics: Biological Products; Cell Line; Cytotoxicity, Immunologic; Humans; Killer Cells, Natural; Lymphocytes, Null; Picibanil; Skin Neoplasms

A 33-year-old woman with malignant melanoma well responded to a chemotherapy including DTIC, ACNU, and VCR, and intralegional injection of OK-432. Four years prior to admission, a lentigo of 5 mm diameter at her left frontal chest was found, but, histological examination resulted in no distinctly malignant findings. In November 1979, multiple subcutaneous tumors appeared over posterior surface of the chest and left axillar region, which were gradually increasing in number and size, then she was admitted to our hospital in June, 1980. Biopsy of subcutaneous tumors revealed a malignant melanoma and its metastasis to skin. Immunochemotherapy was started immediately based upon this diagnoses. The patient received 100mg DTIC i.v. for 4 days, 100mg ACNU i.v. for one day and 1 mg VCR i.v. for one day. OK-432 was locally injected into some tumors as an immunotherapy. On completion of the third course of chemotherapy, all subcutaneous tumors were decreased in size, especially the tumors injected with OK-432. However, patient didn't respond to a repeated chemotherapy, thereafter malignant melanoma was metasized to uterus and peritoneum in May, 1981, and she died in September, 1981. Major side effects of this chemotherapy were nausea and mild transient leukocytopenia. The combination of chemotherapy including DTIC and local injection of OK-432 appeared to be effective for malignant melanoma.

Topics: Adult; Biological Products; Dacarbazine; Drug Therapy, Combination; Female; Humans; Melanoma; Nimustine; Nitrosourea Compounds; Picibanil; Skin Neoplasms; Vincristine

Topics: Adjuvants, Immunologic; Adult; Antineoplastic Agents; Brain Neoplasms; Dacarbazine; Drug Therapy, Combination; Female; Humans; Male; Melanoma; Nimustine; Nitrosourea Compounds; Picibanil; Skin Neoplasms; Vincristine

This study, based on a co-operative group project involving 4 major medical institutes in Japan presents the first survey of malignant melanoma (MM) patients (157 cases) where an attempt was made to systemically evaluate the distribution of primary MM, and the response to DAV-chemoimmunotherapy. The distribution of primary MM in Japan is unique in a sense that the MM involving the lower extremities occupied more than 50% of the total male and female cases. The commonest type and site of involvement is the acrolentiginous MM involving the plantar area (30%). The regimen of our group included the combination of DTIC, VCR and ACNU, a new nitrosourea with or without immunoadjuvants OK-432, PSK, or NK-421). By a historical comparison, the DAV-treated group showed a better prognosis in the survival rates of overall (Stages I-IV) and disseminated (Stages III-IV) patients than those of the non-DAV group. However, the effect of combined immunoadjuvants was not statistically significant, though OK-432 showed a significant inhibition of lymphopenia which always occurred during DAV therapy.

Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Drug Therapy, Combination; Female; Humans; Leucine; Male; Melanoma; Middle Aged; Nimustine; Nitrosourea Compounds; Picibanil; Proteoglycans; Skin Neoplasms; Vincristine

Up to the present no other therapeutic means besides local X-ray or beta-ray irradiation and anticancer drugs for the treatment of patients with mycosis fungoides, especially when the condition has progressed to secondary involvement of the lymph nodes, has been found. A recent clinical trial of OK-432 injected locally into cutaneous tumors of a patient with this disease resulted in a conspicuous contraction not only of the tumors injected but of other tumors as well along with significant regression of lymphadenomas. No serious adverse reaction was observed other than low-grade fever and heavy-headedness. These results suggest host-mediated and direct antitumor effects of OK-432 as the possible underlying mechanisms. The efficacy of OK-432 in reducing the size of the tumors without causing any serious adverse effects indicate the potential usefulness of this drug for the treatment of mycosis fungoides.

Topics: Antineoplastic Agents; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunohistochemistry; Injections, Intralesional; Japan; Middle Aged; Mycosis Fungoides; Neoplasm Staging; Picibanil; Risk Assessment; Skin Neoplasms; Treatment Outcome