A Comparison of the Efficacies of OK-432 and Talc Slurry for Pleurodesis in Patients with Prolonged Air Leak after Pulmonary Resection.

PURPOSE: A prolonged air leak (PAL) is one of the common postoperative complications of pulmonary resection. The aim of this study was to evaluate the efficacy and safety of pleurodesis with sterile talc or OK-432 for postoperative air leak. METHODS: Patients with postoperative air leak who received chemical pleurodesis using sterile talc or OK-432 were retrospectively identified from medical records data. For pleurodesis with either agent, prior assessment and approval by the hospital safety department were carried out for each case, in addition to individual consent. RESULTS: Between February 2016 and June 2022, 39 patients had PALs and underwent chemical pleurodesis. Among them, 24 patients received pleurodesis with talc (Talc group) and 15 with OK-432 (OK-432 group). The leak resolved after less than two pleurodesis treatments in 22 patients (91.7%) in the Talc group compared with 14 patients (93.3%) in the OK-432 group. Pleurodesis significantly increased white blood cell counts, C-reactive protein concentration, and body temperature in the OK-432 group compared with that in the Talc group (p <0.001, p = 0.003, and p <0.001, respectively). CONCLUSIONS: Pleurodesis with talc may be an effective treatment option for postoperative air leak. Our findings suggest that talc was as effective as OK-432 and resulted in a milder systemic inflammatory response.

OK-432 Treatment of Early Fetal Chylothorax: Pregnancy Outcome and Long-Term Follow-Up of 14 Cases.

BACKGROUND: The treatment options for fetal chylothorax include thoracocentesis, thoracoamniotic shunting, and pleurodesis using OK-432. Knowledge on the long-term outcomes after treatment with OK-432 is limited. OBJECTIVE: The aim of this study was to assess the long-term outcomes of children treated in utero with OK-432. METHODS: We performed follow-up on pregnancies and children treated in utero with OK-432 between 2003 and 2009 at Copenhagen University Hospital Rigshospitalet for pleural effusions at gestational age (GA) 16+0-21+6 weeks. Anamnestic information, physical examination, pulmonary function test, neuropediatric examination, and intelligence testing using the Wechsler Intelligence Scale were used for evaluation. RESULTS: Fourteen cases, all chylothorax, were treated with OK-432. None had preterm premature rupture of membranes (PPROM), and the median GA at delivery was 38+5 (24+4-41+5) weeks. Twelve children were eligible for follow-up. The median age at follow-up was 11.4 (7.8-13.8) years. Pulmonary function was normal in all children and the mean full-scale IQ did not differ from that of normal children. Four children had a diagnosed medical condition, attention deficit disorder, or genetic syndrome. The remaining children had normal follow-up. CONCLUSION: Children treated with OK-432 have comparable survival rates and long-term neurodevelopmental outcomes to those treated with thoracoamniotic shunts. There seems to be a lower risk of procedure-related PPROM.

OK-432 pleurodesis for the treatment of pneumothorax in patients with interstitial pneumonia.

BACKGROUND: Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin. METHODS: We retrospectively evaluated the efficacy and safety of pleurodesis using OK-432 in 39 patients treated for IP-related pneumothorax between January 2006 and May 2017. Five to 10 Klinische Einheit (KE) of OK-432 was injected through the chest tube of each patient. Pleurodesis was considered successful if 1) the chest tube was removed without air leaks and 2) there was no recurrence of pneumothorax within 4 weeks after tube removal, and no additional treatment was required. RESULTS: OK-432 pleurodesis was performed 46 times in 39 patients. The median number of OK-432 intrapleural injections received was 1 (range, 1-6), and median dose was 10 KE (range, 5-55 KE). The success rate was 63% (29/46) and recurrence rate was 17.4% (8/46). Grade 5 adverse events were observed in eight patients, including two patients who developed acute exacerbation of IP. Patients in whom the first OK-432 pleurodesis was successful had a significantly longer median survival time than patients in whom it was unsuccessful (322 days vs. 70 days, p = 0.036). CONCLUSIONS: Our results show that OK-432 pleurodesis is an effective treatment for pneumothorax associated with IP; however, clinicians should be aware of the possibility of adverse events, especially in patients who are critically ill.

Experience with OK-432 in lymphatic vascular malformations in a hospital from northern Mexico. / Experiencia con OK-432 en malformaciones vasculares linfáticas en un hospital del norte de México

Background: Lymphatic vascular malformations (LVM) or formerly called lymphangiomas are congenital malformations present in about 1 out of 6000 to -16000 births. The most relevant classification system for lymphangioma management is based on the size of the cysts. Spontaneous resolution is uncommon; thus, expectant management is not recommended. The classic treatment is excisional surgery, but it can affect adjacent structures or have relapses, so, sclerosing substances like OK-432 are being studied. The majority of the studies are small in number of patients and are from Japan; the largest studies in Mexico are focused on specific lesions (macrocystic) or a determined anatomical region. To date, there are no studies of the population of the north of Mexico. Method: The experience with OK-432 was described through a retrospective, descriptive study in patients with LVM, from 2011 to 2016, in a reference hospital of northern Mexico. Results: A total of 26 patients with LVM were treated with OK-432. The majority of the lesions were macrocystic (69 %), microcystic (19 %) and mixed (12 %). From the total number of patients, 11 fully healed, and 72 % of the study population had >50 % reduction in lesion size, with only 2 applications. There were no recurrences. Complications were reported in 2 patients who had skin hyperpigmentation. Conclusions: OK-432 probed to be an effective treatment for LVM in a reference hospital in the north of Mexico.

Introducción: Las malformaciones vasculares linfáticas (MVL), anteriormente llamadas linfangiomas, son malformaciones congénitas que se presentan en uno de cada 6,000 a 16,000 nacimientos. El sistema de clasificación más útil para el manejo del linfangioma se basa en el tamaño de los quistes. La resolución espontánea es infrecuente, por lo que el tratamiento expectante no se recomienda. El tratamiento clásico es la cirugía de escisión, pero puede afectar a estructuras vecinas o haber recidivas, por lo que se empezaron a estudiar sustancias esclerosantes, como el OK-432. La mayoría de los estudios incluyen pocos pacientes; los más grandes realizados en México se enfocan a lesiones específicas (macroquísticas) o únicamente a una región anatómica. Hasta la fecha, no existen estudios del uso de este fármaco en la población del norte de México. Método: Se describe la experiencia con OK-432 mediante un estudio retrospectivo, descriptivo, en los pacientes con MVL, de 2011 a 2016, en un hospital de referencia del norte de México. Resultados: Veintiséis pacientes con MVL recibieron tratamiento con OK-432. La mayoría fueron macroquísticos (69%), microquísticos (19%) y mixtos (12%). Del total de pacientes, 11 presentaron curación total. El 72% de la población estudiada tuvo una reducción de > 50% del tamaño de las lesiones con solo dos aplicaciones de tratamiento; no se presentaron recidivas. Se reportaron complicaciones en dos pacientes (hiperpigmentación de la piel). Conclusiones: El manejo con OK-432 demostró ser efectivo para el tratamiento de las MVL en un hospital de referencia del norte de México.

Experiencia con OK-432 en malformaciones vasculares linfáticas en un hospital del norte de México / Experience with OK-432 in lymphatic vascular malformations in a hospital from northern Mexico

Resumen Introducción: Las malformaciones vasculares linfáticas (MVL), anteriormente llamadas linfangiomas, son malformaciones congénitas que se presentan en uno de cada 6,000 a 16,000 nacimientos. El sistema de clasificación más útil para el manejo del linfangioma se basa en el tamaño de los quistes. La resolución espontánea es infrecuente, por lo que el tratamiento expectante no se recomienda. El tratamiento clásico es la cirugía de escisión, pero puede afectar a estructuras vecinas o haber recidivas, por lo que se empezaron a estudiar sustancias esclerosantes, como el OK-432. La mayoría de los estudios incluyen pocos pacientes; los más grandes realizados en México se enfocan a lesiones específicas (macroquísticas) o únicamente a una región anatómica. Hasta la fecha, no existen estudios del uso de este fármaco en la población del norte de México. Método: Se describe la experiencia con OK-432 mediante un estudio retrospectivo, descriptivo, en los pacientes con MVL, de 2011 a 2016, en un hospital de referencia del norte de México. Resultados: Veintiséis pacientes con MVL recibieron tratamiento con OK-432. La mayoría fueron macroquísticos (69%), microquísticos (19%) y mixtos (12%). Del total de pacientes, 11 presentaron curación total. El 72% de la población estudiada tuvo una reducción de > 50% del tamaño de las lesiones con solo dos aplicaciones de tratamiento; no se presentaron recidivas. Se reportaron complicaciones en dos pacientes (hiperpigmentación de la piel). Conclusiones: El manejo con OK-432 demostró ser efectivo para el tratamiento de las MVL en un hospital de referencia del norte de México.

Abstract Background: Lymphatic vascular malformations (LVM) or formerly called lymphangiomas are congenital malformations present in about 1 out of 6000 to -16000 births. The most relevant classification system for lymphangioma management is based on the size of the cysts. Spontaneous resolution is uncommon; thus, expectant management is not recommended. The classic treatment is excisional surgery, but it can affect adjacent structures or have relapses, so, sclerosing substances like OK-432 are being studied. The majority of the studies are small in number of patients and are from Japan; the largest studies in Mexico are focused on specific lesions (macrocystic) or a determined anatomical region. To date, there are no studies of the population of the north of Mexico. Methods: The experience with OK-432 was described through a retrospective, descriptive study in patients with LVM, from 2011 to 2016, in a reference hospital of northern Mexico. Results: A total of 26 patients with LVM were treated with OK-432. The majority of the lesions were macrocystic (69 %), microcystic (19 %) and mixed (12 %). From the total number of patients, 11 fully healed, and 72 % of the study population had >50 % reduction in lesion size, with only 2 applications. There were no recurrences. Complications were reported in 2 patients who had skin hyperpigmentation. Conclusions: OK-432 probed to be an effective treatment for LVM in a reference hospital in the north of Mexico.

Feasibility and Immune Response of WT1 Peptide Vaccination in Combination with OK-432 for Paediatric Solid Tumors.

BACKGROUND/AIM: Wilms' tumor 1 (WT1) peptide-based vaccination has been reported for its potential usefulness in targeting several cancers. The adjuvant drug OK-432 is known to have potent immunomodulation and therapeutic properties when applied in cancer treatment and may, thus, be important to trigger the appropriate immunological response in paediatric patients with a solid tumor that are vaccinated with a WT1 peptide. PATIENTS AND METHODS: Paediatric patients with a solid tumor were vaccinated with a WT1 peptide and OK-432 once every 2 weeks, for a total of seven times. RESULTS: Of the 24 patients, 18 completed the scheduled vaccinations. Sixteen patients had local skin symptoms and/or fever. In 1 patient, anaphylactic symptoms emerged at the time of the final injection, but these quickly subsided after the treatment. WT1-specific immunological responses were observed in 4 patients (22.2%). WT1 and HLA class I expression were confirmed in 100% and 85% of primary tumors, respectively. CONCLUSION: WT1 peptide vaccine therapy combined with OK-432 appears to be relatively safe for children. However further studies in a larger number of patients are necessary to confirm its safety and efficacy.

Risk Factors for Chest Pain and Fever in Patients Undergoing Pleurodesis with OK-432.

Objective In Japan, pleurodesis is often performed using OK-432. However, OK-432 may cause severe chest pain and fever. The risk factors for these complications are unclear. The aim of this study was to identify the risk factors for chest pain and fever caused by pleurodesis with OK-432. Methods The clinical data of 94 patients who underwent pleurodesis with OK-432 were retrospectively analyzed. Patients who developed chest pain (indicated by a record of rescue pain medication) and/or fever (a recorded temperature of >38°C) were identified. A logistic regression analysis was performed to determine the risk factors for these complications. Results Rescue medication for chest pain was required by 43.6% of the patients and 40.4% developed pyrexia after pleurodesis with OK-432. The univariate analysis showed that the likelihood of requiring rescue medication for chest pain was significantly increased in patients of <70 years of age (p=0.028) and in those who were not premedicated with a nonsteroidal anti-inflammatory drug (NSAID; p=0.003). Age <70 years (adjusted odds ratio 2.97, 95% confidence interval 1.10-8.00, p=0.031) and a lack of premedication with an NSAID (adjusted odds ratio 4.21, 95% confidence interval 1.47-12.04, p=0.007) remained significant factors in a multivariate analysis. The absence of NSAID premedication was the only statistically significant risk factor for fever in the univariate analysis (p=0.034). The multivariate analysis revealed no significant risk factors for fever. Conclusion The results of the present study suggest that premedication with an NSAID might be useful for preventing the chest pain caused by pleurodesis with OK-432. Furthermore, caution is advised when managing chest pain in adults of <70 years of age. Prospective studies should be performed to further investigate this issue.

Life-Threatening Hemolytic Anemia after Intrapleural Instillation of OK-432 for Treatment of Congenital Chylothorax.

Recent reports have advocated treatment of congenital chylothorax with chemical pleurodesis via intrapleural administration of OK-432. Severe complications have not been reported, but recently we have encountered a life-threatening case of massive hemolysis after the procedure. The hemoglobin of the infant decreased from 8.7 to 3.1 g/dl within 48 h, with concomitant severe hyperbilirubinemia (472 µmol/l) requiring exchange transfusion. Frontline neonatologists should be aware of this rare but potentially life-threatening adverse reaction. In addition, it is possible that a longer indwelling time (3.5 vs. 0.5 h) for OK-432 pleurodesis may alter the therapeutic response.

Tratamento intralesional de malformações linfáticas com ênfase na escleroterapia com picibanil (OK-432): revisão sistemática / Intralesional treatment of lymphatic malformations with emphasis on Picibanil (OK-432) sclerotherapy: a systematic review

INTRODUÇÃO: Conduziu-se revisão sistemática retrospectiva da literatura incluindo estudos relatando o uso de picibanil para tratar malformações linfáticas (ML). MÉTODOS: A pesquisa foi realizada com estudos publicados no PubMed de janeiro de 1990 a 14 de abril de 2013. Na estratégia de busca, usou-se os descritores "OK-432" ou "Picibanil" e "lymphatic malformation". Os seguintes elementos foram comparados aos de outras modalidades relatadas e, então, compilados: mecanismo de ação, indicações, contraindicações, eficácia, administração, efeitos colaterais, complicações, vantagens e desvantagens. RESULTADOS: Foram encontrados 44 estudos, 27 dos quais atenderam aos critérios de inclusão. O picibanil é uma preparação liofilizada de uma cepa de baixa virulência de Streptococcus pyogenes inativada pela penicilina G. Seu mecanismo de ação ainda não definido claramente, mas especula-se que provoque uma resposta inflamatória controlada com adesão das paredes dos cistos. O picibanil é indicado quase que unanimemente para o tratamento da ML macrocística, cuja resposta é mais efetiva do que em lesões microcísticas ou mistas. Em geral, o picibanil é administrado por meio de punção com visualização direta ou guiada por ultrassonografia, com o paciente sob anestesia geral. A preparação comumente utilizada consiste em 0,1 mg de picibanil em 10 ml de soro fisiológico. Os efeitos colaterais são, em geral, leves; sendo dor, inchaço e febre os mais frequentemente relatados. CONCLUSÃO: Os estudos apresentam pouca evidência científica. A revisão sistemática identificou que o picibanil é útil no tratamento da ML de qualquer tipo, mas tem resultados melhores em lesões macrocísticas. A eficácia foi comparável à de outras terapias. Não foi apresentada nenhuma contraindicação específica. Embora o mecanismo de ação ainda não tenha sido determinado, o picibanil trata-se de opção de tratamento.

INTRODUCTION: We performed a retrospective systematic review of studies reporting the use of Picibanil for treatment of lymphatic malformations (LMs). METHODS: We searched the PubMed database for available studies, including those published between January 1990 and April 14, 2013. The search strategy involved the use of the keywords "OK-432" or "Picibanil" and "lymphatic malformation." Information was compiled regarding the reported mechanism of action, indications, contraindications, efficacy, administration, side effects, complications, and advantages and disadvantages compared to those of other modalities. RESULTS: Forty-four studies were found, of which 27 fulfilled the inclusion criteria. Picibanil is a lyophilized preparation of a low-virulence strain of Streptococcus pyogenes inactivated with penicillin G. Its mechanism of action is unclear, but it has been speculated that it causes a controlled inflammatory response with adhesion of cyst walls. Picibanil is almost unanimously indicated for the treatment of macrocystic LMs, which show a greater effectiveness response compared to that shown by microcystic or mixed LMs. Picibanil is usually administered by puncturing, either with direct visualization or guided by ultrasound, with the patient under general anesthesia. The most widely used preparation comprises 0.1 mg of Picibanil in 10 mL of saline. Side effects are mostly mild, with pain, swelling, and fever being the most frequently reported. CONCLUSION: The studies had low scientific evidence. A systematic review found that Picibanil is useful against any LM, with better results in macrocystic lesions. Efficacy was comparable to that of other therapies. No specific contraindication was presented. Although the mechanism of action has not been established, the inclusion of Picibanil as a treatment option is warranted.

Effectiveness of OK-432 (Sapylin) to reduce seroma formation after axillary lymphadenectomy for breast cancer.

BACKGROUND: The occurrence of seroma formation after axillary lymphadenectomy for breast cancer cannot be ignored. Various approaches have been used in an effort to reduce it, but these results are still controversial. We aimed to describe a new method of application of OK-432 (Sapylin, heat-treated Su strain of Streptococcus) to reduce seroma formation after axillary lymphadenectomy for breast cancer and to verify the safety and efficacy of it as a beneficial supplement for conventional surgery. METHODS: A prospective, randomized analysis of consecutive quadrantectomy or mastectomy plus axillary lymphadenectomy using or not using OK-432 was designed. From July 2010 to November 2011, a total of 111 patients were enrolled in this prospective, randomized study and completed the follow-up. OK-432 applied to the axillary fossa plus placement of closed suction drainage was used in 54 patients (the experimental group); placement of closed suction drainage was used in 57 patients (the control group). RESULTS: There were no statistical significance between the two groups in terms of age, body mass index, treatment received, tumor size, number of removed lymph nodes, and lymph node status. Postoperative drainage magnitude and duration were significantly reduced in the experimental group (P = 0.008 and 0.003, respectively). One week after hospital discharge, fewer patients developed a palpable seroma in the experimental group: 10 in the experimental group versus 28 in the control group (P = 0.001). Fewer seromas needed aspiration (mean 1 [range 0-3] in the experimental group vs. mean 4 [range 1-5] in the control group; P < 0.001). There were no significant differences in terms of the incidence of complications associated with axillary lymphadenectomy (P = 0.941). CONCLUSIONS: OK-432 is a feasible and safe option for axillary lymphadenectomy for breast cancer. The use of it does not always prevent seroma formation, but it can reduce drainage magnitude and duration, as well as decrease the incidence of seroma after the removal of drainage. It may be increasingly conducted in day surgery clinics.

Intrathoracic administration of OK-432 elevates the serum procalcitonin levels.

OBJECTIVE: The intrathoracic administration of OK-432, a lyophilized preparation of the heat- and penicillin-treated Su-strain of type 3, group A Streptococcus pyogenes, is performed in Japan for pleurodesis of malignant pleural effusion or pneumothorax. Persistent fever is often observed after pleurodesis. To elucidate whether procalcitonin (PCT) is useful for distinguishing between the side effects of OK-432 and infection, we measured the serum PCT levels before and after pleurodesis. METHODS: We performed a prospective study of 12 patients with refractory pleural effusion or pneumothorax who required pleurodesis using OK-432 between August 2011 and February 2012. The serum PCT and C-reactive protein (CRP) levels were measured on days 1 and 3. RESULTS: Of the 12 patients, five had pneumothorax and seven had uncontrolled pleural effusion with carcinomatous pleurisy. The median serum levels of PCT and CRP increased from 0.055 to 1.59 ng/mL (p=0.0022) and from 1.52 to 16.82 mg/dL (p=0.0022), respectively. The fevers subsided without antibiotic administration. CONCLUSION: The serum PCT level may not be useful for distinguishing fever caused by side effects of OK-432 from that caused by bacterial infection. The intrathoracic administration of OK-432 increased the serum levels of both PCT and CRP in the absence of any bacterial infection.

[Unsuccessful treatment with OK-432 picibanil for orbital lymphangioma]. / Resultado sin éxito en el tratamiento de un linfangioma orbitario con OK-432. Picibanil.

INTRODUCTION: Lymphangioma is a malformation of the lymphatic system. The classic approach is surgery. We report a case of orbital lymphangioma in a girl who was given OK-432 to avoid surgery and its complications. DISCUSSION: OK-432 is a lyophilized mixture of group A Streptococcus pyogenes which produces a fibrosis limited to the lesion with a high cure rate. The main advantages are the easy intra-lesional application. with no scars and or damage of closed areas. Its main disadvantage is a significant local inflammatory reaction.

Intrapleural chemo- and hyperthermotherapies for malignant pleural effusion: a randomized prospective study.

OBJECTIVE: The current prospective randomized study was designed to evaluate the safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil) plus hyperthermotherapy in patients with malignant pleural effusion (MPE). METHODS: A total of 358 patients with MPE due to end-stage malignancies were enrolled and randomly divided into two groups, A and B: the intrapleural combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea, vomiting or anorexia, bone marrow depression, and pyrexia were similar in both groups. RESULT: Patients in Group A (with hyperthermotherapy) showed a significantly higher overall response (93.4%) compared to those in Group B (79.8%, χ(2) = 43.11, p < .05). The median survival time for patients in Group A and Group B were 8.9 and 6.2 months, respectively (p > .05). After treatment, the quality of life scores were significantly increased in both groups as compared to prior treatment (p < .05). CONCLUSION: In conclusion, our study suggests that combined intrapleural cisplatin and OK-432 followed by hyperthermotherapy are more effective in the control of MPE and improve patients' quality of life.

[Severe iatrogenic airway obstruction due to lingual lymphangioma]. / Obstruction iatrogène sévère de la voie aérienne par un lymphangiome lingual.

Lymphangioma of the tongue is a rare and benign tumour involving congenital and cystic abnormalities derived from lymphatic vessels. Treatment modalities include surgery and a large number of different intralesional injections of sclerosing agents. Presently, OK-432 (Picibanil(®)) is the preferred sclerosant and when administered intralesionally will result in inflammation, sclerosis, and cicatricial contraction of the lesion. We report a case of microcystic lymphangioma of the tongue in a 5-year-old boy treated with an intralesional injection of OK-432. In the immediate postoperative period, the patient suffered severe diffuse swelling, progressive upper airway obstruction with inspiratory stridor, and respiratory distress requiring emergency fiberoptic nasotracheal intubation. Although OK-432 injections are found to be safe and effective as a first line of treatment for lymphangiomas, local swelling with potentially life-threatening airway compromise should be anticipated, especially when treating lesions near the upper airway.

Sclerotherapy for lymphatic malformations in children: a scoping review.

PURPOSE: This scoping review assesses the literature and summarizes the current evidence on sclerotherapy for the treatment of lymphatic malformations in pediatric patients. METHODS: A comprehensive search of published and unpublished literature was conducted using multiple databases. Title, abstract, and full-text screening was conducted by 2 independent clinicians. All discrepancies were resolved during consensus meetings. RESULTS: A total of 182 articles were retrieved. Forty-four articles were removed as duplicates, and 11 articles were added after reviewing prominent studies. After full-text abstraction, 44 articles and 2 conference proceedings (N = 882 patients) were included in the final results. Twelve articles were classified as level II and 34 articles as level IV evidence. Picibanil (OK-432) was the primary agent used in most included studies. Postinjection symptoms with OK-432 were primarily fever, swelling, and erythema at the site. Life-threatening complications were uncommon and involved postinjection swelling of cervical lesions causing airway compromise. CONCLUSIONS: The literature regarding sclerotherapy for lymphatic malformations is of a low level of evidence and suffers from a lack of standardization. Randomized clinical trials focused on OK-432, bleomycin, or alcoholic solution of zein; standardized dosing protocols; and consistent and reliable outcome reporting will be necessary for further development of treatment guidelines.

Treatment of lymphatic malformations of head and neck with OK-432 sclerotherapy induce systemic inflammatory response.

Systemic immune responses after OK-432 (Picibanil) sclerotherapy in patients with head and neck lymphatic malformations (LM) were examined to achieve a better understanding of the mechanism of OK-432 sclerotherapy and to evaluate the long-term treatment outcome. Serum samples from 17 consecutive patients with head and neck LMs were collected during a total of 26 OK-432 treatment episodes. Serum C-reactive protein (CRP), interleukins (IL) 1ß, 6, 8, 10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, RANTES, immune protein (IP)-10 and macrophage chemoattractant protein (MCP)-1 as well as blood leukocyte counts were determined. Clinical outcome of the treatment was evaluated at the last visit and from patient files. Elevated serum levels of IP-10 (means at baseline 702 ng/L, after 1 day 1180 ng/L, after 4 weeks 691 ng/L) were seen on day one after OK-432 sclerotherapy (p < 0.05). C-reactive protein and leukocyte counts 1 day after treatment differed statistically significantly (p < 0.05) from the baseline. No significant differences with other cytokines investigated were observed. Patients with macrocystic LM responded better than patients with microcystic LM (p = 0.01). The elevated levels of IP-10, C-reactive protein and leukocyte levels indicate that OK-432 sclerotherapy induces systemic immune responses in patients with LM. The mechanisms of OK-432 sclerotherapy are still not precisely understood, but the IP-10 elevation may reflect local antiangiogenetic properties of immunoactivation induced by OK-432.

Treatments of various otolaryngological cystic diseases by OK-4321: its indications and limitations.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the indications for, and outcomes and limitations of, OK-432 therapy in various otolaryngological cystic diseases. STUDY DESIGN: A retrospective clinical study at Yamagata University School of Medicine and the Fukase Clinic in Japan. METHODS: Between April 1996 and November 2009 we tried OK-432 therapy in 148 patients with otolaryngological cystic diseases. In cases of plunging ranulas, lymphangiomas, branchial cleft cysts, thyroglossal duct cysts, thyroid cysts, and cervical lymphocele, we aspirated as much of the fluid content of each cystic lesion as possible, and we then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. RESULTS: Disappearance of the lesion was observed in 119 of 148 patients (80%). Marked reduction was observed in 20 of 148 patients (14%). Partial reduction was observed in four patients (3%), and no response was seen in five patients (3%). Plunging ranula, lymphangioma, thyroglossal duct cyst, thyroid cyst, auricular hematoma, and salivary mucocele showed better responses to OK-432 therapy than did branchial cleft cyst. Serious complications with OK-432 therapy were infrequent, and the therapy seemed to have no influence on future surgery. CONCLUSIONS: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of various otolaryngological cystic diseases.

Effects and mechanism of OK-432 therapy in various neck cystic lesions.

CONCLUSION: Our results confirmed that OK-432 therapy is simple, easy, safe, and effective and can be used as a substitute for surgery in the treatment of benign neck cysts. In OK-432 therapy, inflammatory cytokines may play important roles in shrinkage of the cystic spaces. OBJECTIVE: The aim of this study was to evaluate the outcome and mechanism of action of OK-432 therapy in benign neck cysts. METHODS: We tried OK-432 therapy in 83 patients with benign neck cysts between April 1997 and August 2009. We aspirated as much of the fluid content of each cystic lesion as possible, and then replaced the volume of aspirated fluid with about half the volume of OK-432 solution. We evaluated the mechanism of action of OK-432 in 43 of the patients. The intracystic fluid in the cysts was aspirated before and after OK-432 therapy, and cytokine production in each aspirate was analyzed by ELISA. RESULTS: Disappearance of the lesion was observed in 63 of 83 patients (76%). Marked reduction was observed in 13 of the 83 patients (16%). Partial reduction was observed in two patients (2%) and no response was seen in five (6%). Local discomfort at the injection site and low-grade fever were side effects observed in half of the patients, but such problems resolved within a few days. No local scarring or deformity of the injected sites occurred in any patient. We performed OK-432 therapy on an outpatient basis without hospitalization. Levels of various cytokines, including tumor necrosis factor, interleukin-8, interleukin-6, interferon gamma, and vascular endothelial growth factor, were significantly elevated in each aspirate after OK-42 therapy.

Experimental intraperitoneal infusion of OK-432 in rats: evaluation of peritoneal complications and pathology.

PURPOSE: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. MATERIALS AND METHODS: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. RESULTS: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. CONCLUSION: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications.