Injection Of OK-432 Research Articles

Treatment of lymphangiomas by means of sclerotherapy with OK-432 (Picibanil®) is safe and effective – A retrospective case series

IntroductionCongenital cystic lymphangiomas (CCL) or lymphatic malformations (LMs) are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. MethodsIn a single center retrospective study we analyzed 37 consecutive patients (30 children, 3 adolescents and 4 adults) who were diagnosed with lymphangioma and subsequently treated with OK-432 (Picibanil®) in a general hospital between October 2000 and November 2021. ResultsThe median follow-up period was 2.5 months (range 0.7–56.7 months). The lymphangiomas were localized in the head and neck region (n = 25), the thorax/abdomen (n = 6) and extremities (n = 6). The majority of patients had 1 injection with OK-432 (n = 28), five patients had 2 injections, three patients had 3 injections and one patient had more than 3 injections. The most common complications were swelling (89%), fever (81%), redness at the injection site (81%) and pain (73%). The response to therapy was excellent or good in 32 patients (86.4%), 2 patients had a medium response and 3 patients did not show any response. The clinical reaction after the instillation of OK-432 is not predictive for the quality of outcome. ConclusionThe application of Picibanil is safe and without serious side effects. Parents and patients prefer local sclerotherapy versus surgery as it has less complications. We therefore suggest that Picibanil sclerotherapy should be the first-line treatment for macrocystic and mixed type lymphangiomas.

A case of sublingual ranula that successfully responded to micro-marsupialisation under COVID-19 infection: A case report

Ranula is a mucous retention cyst caused by the extravasation of mucus from the sublingual gland. We present a case of sublingual ranula that was successfully treated with micro-marsupialisation under COVID-19 infection. The patient was a 17-year-old Japanese male suffering from a sublingual ranula that did not improve after several rounds of puncture-aspiration therapy. The patient underwent OK-432 injection therapy under hospitalisation. However, the swelling worsened. Thus, micro-marsupialisation was subsequently performed. After micro-marsupialisation, the lesions flattened out, but 14 days after treatment, the patient was found to have asymptomatic COVID-19 infection when he underwent polymerase chain reaction testing as a close contact person. Simultaneously, the lesion re-swelled and became painful, so non-steroidal anti-inflammatory drugs were prescribed. The next day, the sutures spontaneously detached, viscous saliva and blood overflowed, and the ranula disappeared. Micro-marsupialisation is effective and useful even if the patient has a COVID-19 infection.

Multimodal treatment of cystic lymphangioma – A challenge

Congenital cystic lymphangiomas or lymphatic malformations are benign malformations due to a developmental disorder of lymphatic vessels. The most frequent localization of lymphangiomas is the neck and head region. The fact that the lesions usually have no spontaneous regression, tend to augment in size and may cause life-threatening complications such as occlusion or infiltration of neighbouring organs and structures, underlines the need of an early adequate therapy. Surgical excision used to be the first-line treatment of lymphangiomas. However, complete excision often is not possible. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. We present two cases of lymphangioma which were challenging to manage, yet the results were good in one case and excellent in the other case (according to the Acevedo classification). Sclerotherapy with Ok-432 is recommended primary for macrocystic lymphangiomas. The application is safe and without serious side effects. It can be used alone or in combination with other treatment modalities.

Video assisted sclerosis of endoabdominal lymphangiomas with OK432: An effective, safe and minimally invasive choice

Abstract Lymphatic malformations (LM) or lymphangiomas are congenital errors in vascular embryogenesis. Percutaneous sclerosis is considered the best treatment for LM with external localization and yields excellent results. Surgical resection for deep LM is currently the mainstay of therapy, but high recurrence and morbidity rates are reported. Uniform therapeutic protocols are still unavailable. We describe two cases of abdominal LM treated by video-assisted sclerosis with OK432. The first case was a 5-month-old girl with pre-natal diagnosis of a left retroperitoneal LM with vascular encasement. A laparoscopic approach was used to expose the mass and a video-assisted injection of OK-432 in major cysts was performed. A remarkable reduction of the lesion size was observed after 18 months. The second case was a 15-year-old boy who presented at the ER acute abdominal pain. A mesenteric LM was diagnosed and a video-assisted sclerosis of the lesion with OK432 was performed. The LM completely disappeared. Follow-up was of 12 months. In our experience, video-assisted sclerosis of abdominal LM with OK-432 is a valid alternative to surgical resection. The procedure is feasible, safe, effective and minimally invasive; complete resolution may be observed in some cases. Long-term follow-up is required to rule out recurrences.

An adult submandibular cystic lymphangioma successfully treated with local injection of OK-432: a case report

An adult submandibular cystic lymphangioma successfully treated with local injection of OK-432: a case report

Lymphangioma and ranula treated by OK-432 injection therapy in children : A report of five cases

Lymphangioma and ranula treated by OK-432 injection therapy in children : A report of five cases

Promising abscopal effect of combination therapy with thermal tumour ablation and intratumoural OK-432 injection in the rat osteosarcoma model

Treatment options for metastatic osteosarcoma are limited. The present study aimed to evaluate whether radiofrequency ablation (RFA) combined with intratumoural OK-432 injection induces systemic anti-tumour immunity in rat osteosarcoma model. Eighty of 145 rats were assigned to four groups to evaluate overall survival and tumour size: control (no treatment), RFA-only, OK-432, and RFA-OK-432. The remaining 65 were assigned for histological examination. Maximum diameters of tibial and lung tumours were determined. Tumour samples were histologically examined using haematoxylin-eosin and immunohistochemical staining. Overall survival was significantly prolonged in the RFA-OK-432 group compared to the RFA-only and OK-432 groups. Only rats in the RFA-OK-432 group exhibited significant decreases in maximum tumour diameter after treatment. Ki-67-positive tumour cells in the RFA-OK-432 group were significantly stained negative on immunohistochemical analysis as opposed to those in the RFA-only and OK-432 groups. The number of CD11c+, OX-62+, CD4+, and CD8 + cells significantly increased in the RFA-OK-432 group compared to the RFA-only group. RFA with intratumoural OK-432 injection resulted in distant tumour suppression, prolonged survival, and increased dendritic cells, cytotoxic T cells, IFN-γ, and TNF-α, whereas RFA or OK-432 alone did not produce this effect. This combination may induce an abscopal effect in human osteosarcoma.

Microbubbles in macrocysts \u2013 Contrast-enhanced ultrasound assisted sclerosant therapy of a congenital macrocystic lymphangioma: a case report

BackgroundCongenital cystic lymphangiomas are benign malformations due to a developmental disorder of lymphatic vessels. Besides surgical excision, sclerosant therapy of these lesions by intracavitary injection of OK-432 (Picibanil®), a lyophilized mixture of group A Streptococcus pyogenes, is a common therapeutical option. For an appropriate application of OK-432, a detailed knowledge about the structure and composition of the congenital cystic lymphangioma is essential. SonoVue® is a commercially available contrast agent commonly used in sonography by intravenous and intracavitary application.Case presentationHere we report the case of 2 month old male patient with a large thoracic congenital cystic lymphangioma. Preinterventional imaging of the malformation was performed by contrast-enhanced ultrasound after intracavitary application of SonoVue® immediately followed by a successful sclerotherapy with OK-432.ConclusionsContrast agent-enhanced ultrasound imaging offers a valuable option to preinterventionally clarify the anatomic specifications of a congenital cystic lymphangioma in more detail than by single conventional sonography. By the exact knowledge about the composition and especially about the intercystic communications of the lymphangioma sclerosant therapy becomes safer and more efficient.

Therapeutic Ultrasound-Induced Antitumor Immune Response and Enhanced by Immunostimulant for Tumor Treatment

To evaluate whether antitumor immunity is enhanced systemically by combining pulsed-wave ultrasound hyperthermia (pUSHT) and local injection of an immunostimulant, OK-432. BALB/c mice were inoculated CT26-luc-GFP tumors on both flanks as a bilateral tumor model. The treated-side tumor underwent a 10-day treatment with pUSHT and/or subcutaneous injection of OK-432. The untreated-side tumor was regarded as a non-visualized small tumor to assess the degree of anti-tumor immune response. In a rechallenge tumor model, a rechallenge tumor was implanted contralaterally after the treated-side tumor experienced a 5-day treatment and then surgically removed. This model was designed to evaluate the establishment of a long-term active tumor-specific immune memory for preventing tumor recurrence. The tumor growth rate and growth activity of both tumors (treated- and untreated-side) were significantly inhibited with the OK+pUSHT combination treatment. Systemic anti-tumor effect seemed to be prolonged. The results of IF and H&E staining showed that there was a remarkable increase of NK cell infiltration in the tumor center and an earlier necrosis area for the combination treatment. Survival rates significantly increased for the OK+pUSHT group. In the rechallenge test, the volume of all reimplanted tumors decreased and then disappeared as compared with the control group. Combining pUSHT with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.

Evaluation of OK-432 Injection Therapy as Possible Primary Treatment of Intraoral Ranula

A ranula is a pseudocyst caused by mucous extravasation from the sublingual gland. Recently, a sclerosing agent, OK-432 (picibanil), has been reported to be highly effective for treating lymphangioma and cervical cystic lesions. The present study assessed the effectiveness of OK-432 injection therapy for intraoral ranula to clarify whether it can be used as the primary treatment. The present study was a retrospective clinical study of patients with intraoral ranula who received OK-432 injection therapy from 2005 to 2015. The ranula size was measured on computed tomography or magnetic resonance imaging studies. We dissolved 1 Klinische Einheit (KE) unit of OK-432 powder in normal saline equal to the aspiration volume. The primary endpoint was the treatment results. The secondary endpoints were the relation between the treatment results and the lesion length and aspiration volume. A total of 23 patients received OK-432 injection therapy for an intraoral ranula. The mean lesion size was 19.96mm. The mean aspiration volume was 2.14mL. The number of injections was 1 to 4 (mean 1.70). The treatment results were complete regression (CR) in 18 (78.2%), partial regression (PR) in 3 (13.0%), and no response (NR) in 2 (8%) patients after the last injection. The overall efficacy rate was 91.2% (21 of 23). No serious complications were observed. The lesion length and aspiration volume of the CR group was 17.38mm and 1.40mL, respectively. The lesion length and aspiration volume of the PR/NR group was 29.20mm and 4.80mL, respectively. The PR/NR group lesions were significantly larger than the CR group lesions. OK-432 injection therapy for intraoral ranula is safe and effective compared with other surgical therapies. This therapy could potentially become a primary treatment of intraoral ranula.

A Case of Sublingual Ranula That Responded Successfully to Localized Injection Treatment with OK-432 after Healing from Drug Induced Hypersensitivity Syndrome.

A ranula is a mucus retention cyst or pseudocyst caused by leakage of mucus from the sublingual gland and generally occurs in the oral floor. In addition, drug induced hypersensitivity syndrome (DIHS) is a rare but well-recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepatosplenomegaly and oral stomatitis. This paper presents the first case of successfully treated sublingual ranula with localized injection of OK-432 after healing from drug induced hypersensitivity syndrome, which has previously been unreported in the literature. We present the case of a 38-year-old Japanese woman with sublingual ranula that responded successfully to localized injection treatment with OK-432 after healing from drug induced hypersensitivity syndrome. She was affected with cutaneous myositis and interstitial lung disease when she was 26 years old. At the age 34 years, she received additional oral treatment of diaminodiphenyl-sulfone due to deterioration of the cutaneous myositis, which resulted in drug induced hypersensitivity syndrome (DIHS) with severe oral stomatitis. Local injection of OK-432 to the ranula may be a very safe and useful treatment method even if the patient has a history of drug allergy and has connective tissue disease such as cutaneous myositis.

Congenital mucocele of the gland of Blandin-Nuhn.

An infant was born by natural childbirth. He presented with a mucocele on the ventral surface of the tongue. A pediatrician aspirated it and recognized a mucoid liquid. Although it decreased in size, it thereafter became swollen again after 3 months. It was aspirated again, and recognized the same liquid. Because it recurred and had no changes, he visited our hospital 9 months after his birth. On examination, he had a soft and smooth mucocele localized on the ventral surface of the tongue (Fig. 1a). MRI revealed a tumor at the same location, and the tumor was 2.1 × 1.9 × 1.5 cm in size 10 months after his birth. T1-weighted images (TIWI) showed a low intensity, T2WI showed a high and fat suppression and T1WI showed a low intensity. The internal intensity was uniform, and there was no septal structure (Fig. 1b). We diagnosed it to be a congenital mucocele of the gland of Blandin–Nuhn. Although subset of these tumors disappear spontaneously [1], most of them require a complete excision together with the Blandin–Nuhn glandular components. Because it is thin-walled and close to the surface, it tends to rupture easily, recurrence is frequent [2]. Recently, the usefulness of topical injection of OK-432 into the mucocele was reported [3]. Because he had no difficulties in either development or eating, we decided to wait for his growth to proceed while keeping the possibility of surgery in mind. The tumor spontaneously disappeared after 6 months, and at the most recent examination, we observed no recurrence (Fig. 1c). Figure 1: (a) A soft and smooth mucocele is observed on the ventral surface of the tongue. (b) Sagital fat suppression T1WI showed a low intensity. The internal intensity was uniform and no septal structure was observed. (c) The cyst disappeared spontaneously and ... Because only 2.5% of mucoceles arise on the tongue [4], mucoceles of the gland of Blandin–Nuhn are uncommon. They may be the result of trauma to the tongue ventrum that ruptures of the draining ducts [5]. Therefore, they are acquired and there is no indication for the congenital development of them. No ethical approval is required. A.O. is a guarantor of the study.

OK-432囊胞内注入療法による口腔領域囊胞性疾患の治療

OK-432囊胞内注入療法による口腔領域囊胞性疾患の治療

OK432 Versus Doxycycline for Treatment of Macrocystic Lymphatic Malformations

A variety of sclerotherapy agents are used to treat macrocystic lymphatic malformations (LMs). This retrospective study at a single institution was performed to compare the outcomes of pediatric macrocystic LMs of the head and neck that were treated with doxycycline or with OK432. The outcomes measured included early response to therapy, number of treatments required, operating room time, and adverse events. The rates of clinical success for OK432 and doxycycline were similar (83% and 82%, respectively; p > 0.05), although OK432-treated patients required more treatments than did doxycycline-treated patients (1.9 versus 1.0 injections; p = 0.01; 95% confidence interval, 1.57 to 0.27). The average operating room time for a single OK432 injection was significantly shorter than that for doxycycline (53.2 versus 98.1 minutes; p < 0.001); however, when the total number of treatments administered was considered, the overall times in the operating room were similar. Adverse events in the early postoperative period were more common in OK432-treated patients, who experienced marked postoperative swelling compared to doxycycline-treated patients. OK432 and doxycycline are both effective sclerosants for the treatment of predominantly macrocystic LMs. The administration time for OK432 is shorter than that for doxycycline, but OK432 required more treatments overall to achieve clinical success. Early adverse events were more common in OK432-treated patients, but longer follow-up is necessary to determine whether rates of recurrence and adverse events are similar, particularly in light of the risk of tooth discoloration in doxycycline-treated patients.

Octreotide/etilefrine/OK-432併用療法にて治癒した食道癌術後乳糜胸の1例

Octreotide/etilefrine/OK-432併用療法にて治癒した食道癌術後乳糜胸の1例

A new operative strategy for refractory microcystic lymphangioma

The optimal management of microcystic lymphatic malformations (LMs) in children has not been established. We describe how we used the Ligasure™ Vessel Sealing System (LVSS) to achieve partial resection of refractory microcystic LMs in a 1-year-old boy. The child was admitted in respiratory distress caused by infection and swelling of cervical LMs. The LMs had been diagnosed prenatally, but had not decreased in size despite three treatments with OK-432 sclerotherapy. We performed direct dissection of the microcystic LMs using the LVSS with minimal intraoperative blood loss or lymphatic leakage. The LMs were resected as completely as possible without damage to the jugular vein or major nerves. His postoperative course was uneventful. Histological examination revealed complete sealing of the lymphovascular channels with obliterated lumens. Resection using the LVSS is effective and easy to perform for partial resection of microcystic LMs. We recommend the combination of initial OK-432 injection therapy and subsequent partial resection using the LVSS for refractory microcystic LMs.

Complete Resolution of Retroperitoneal Lymphangioma with a Single Trial of OK-432 in an Infant

Retroperitoneal lymphangioma is extremely rare. Although these neoplasms are benign, they can grow progressively with subsequent compression and infiltration of the adjacent structures. Surgical excision is demanding when the lesion surrounds vital structures and it is generally fraught with a high recurrence and morbidity rate. We report the case of a huge retroperitoneal lymphangioma in a newborn treated successfully with intracystic injection of OK-432.

Elevation of serum procalcitonin in patients after chemical pleurodesis with intrapleural injection of OK‐432

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.

Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

Radiofrequency Ablation and Immunostimulant OK-432: Combination Therapy Enhances Systemic Antitumor Immunity for Treatment of VX2 Lung Tumors in Rabbits

To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.