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Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the efficacy of pleurodesis using OK-432 after cardiac surgery in the neonatal period or early infancy., Methods: We retrospectively reviewed the data of 11 consecutive patients who underwent cardiac surgery in the neonatal period or early infancy and pleurodesis using OK-432 for persistent postoperative pleural effusion in two institutions., Results: The median age at surgery was 8 days (interquartile range [IR], 2-18) with a body weight of 2.84 kg (IR, 2.30-3.07). The maximum amount of pleural drainage before pleurodesis was 94.7 (IR, 60.2-107.7) ml/kg/day. Pleurodesis was initiated at postoperative day 20 (IR, 17-22) and performed in bilateral pleural spaces in seven patients and unilateral in four. The median numbers of injection were 4 (IR, 3-6) times per patient and 3 (IR, 2-3) times per pleural space. In 10 patients, pleural effusion was decreased effectively, and drainage tubes were removed without reaccumulation within 15 (IR, 12-28) days after initial pleurodesis. However, in one patient, with severe lymphedema, pleural effusion was uncontrollable, resulting in death due to sepsis. Adverse events were observed in nine patients; temporal deterioration of lung compliance and arterial blood gas occurred in two, insufficient drainage requiring new chest tube(s) in five, temporal atrial tachyarrhythmia in one, and lymphedema in four., Conclusions: Pleurodesis using OK-432 is effective and reliable for persistent postoperative pleural effusion in neonates and early infants. Most of the complications, which derived from inflammatory reactions, were temporary and controllable. However, severe lymphedema is difficult to control., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aims to perform a meta-analysis to figure out the efficacy of OK-432 sclerotherapy between Macrocystic (MAC) lymphangiomas and Microcystic (MIC) lymphangiomas., Methods: We conducted a systematic review and meta-analysis to clarify the relationship between OK-432 and lymphangiomas. PubMed and ISI Web of Science were searched from inception to May 2022. Joanna Briggs Institute (JBI) manual was used to evaluate the risk of bias. We calculated pooled Relative Risks (RR) and 95% Confidence Interval (95% CI) using random effects model to evaluate the relations between OK-432 and lymphangiomas., Results: A total of 11 studies (including 352 cases) about OK-432 sclerotherapy for lymphangioma were included in the current meta-analyses. The results suggested that the efficacy of OK-432 was significantly in MAC lesions than in MIC (RR=1.51, 95% CI 1.298-1.764), with significant moderate degrees of heterogeneity among 11 studies (I 2 =51.2%, p=0.025). Subgroup analyses suggested that there was significant association in both retrospective studies (RR=1.26, 95% CI 1.03-1.53) and classification (by 1 cm) (RR=1.37, 95% CI 1.04-1.80) were associated with the efficacy of OK-432., Conclusion: To our knowledge, our study represents the first meta-analysis examining the efficacy of OK-432 in the treatment of different types of LMs. However, the regional differences and the age differences of the subjects are the main limitations of this study and should be avoided in further research. Our results suggested that OK-432 sclerotherapy for macrocystic lymphangiomas was more effective., (Copyright © 2023 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier España, S.L.U. All rights reserved.)

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.

Background: Primary spontaneous pneumothorax (PSP) commonly occurs in lean, tall, male children and adolescents. To reduce recurrence rates of PSP, chemical pleurodesis could be helpful for patients undergoing video-assisted thoracoscopic surgery (VATS) wedge bullectomy. The efficacy and safety of intraoperative OK-432 (Picibanil) pleurodesis on preventing the recurrence of PSP in pediatric patients remain unclear., Methods: It is a retrospective observational study in a single center, between 2014 and 2020, enrolled 48 (8 females) pediatric PSP patients with persistent air leakage at the mean age of 16.3 ± 1.1 years to receive VATS wedge bullectomy and pleural abrasion. Twenty patients received additional intraoperative OK-432 pleurodesis. The clinical characteristics of patients, surgical outcomes, and recurrence rates were analyzed., Results: The OK-432 group had longer operation time (118.6 ± 35.6 vs. 96.5 ± 23.3 min; p < 0.05) and higher proportion of postoperative fever (75.0% vs. 28.5%; p = 0.015) than the standard group. No serious adverse events were noted and other surgical outcomes in the two groups were comparable. After a mean follow-up period of 18.1 ± 19.1 months, the OK-432 group had a lower recurrence rate compared with the standard group (5% vs. 28.6%; p < 0.05, odds ratio 0.13, 95% confidence interval: 0.01-1.15), but it had no significant difference in statistics on the Kaplan-Meier curves (log-rank p = 0.105)., Conclusion: It was the first study that focused on the addition of intraoperative OK-432 pleurodesis for PSP with persistent air leakage in children and adolescents receiving VATS. It demonstrated the efficacy with a low recurrence rate and short-term safety as a single-center experience., Level of Evidence: Retrospective review, therapeutic study, Level III., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cystic hygroma is one type of the benign malformations and typically located in the neck, clavicle, and others, in children under the age of 5 years. However, the incidence of giant cervicomediastinal giant cystic hygroma is very rare, especially in adulthood. Such a location and age make its diagnosis difficult because they are usually asymptomatic. Complete surgical resection seems impossible while multiple sites are involved. Herein, we present a case of giant cervicomediastinal cystic hygroma, describing the clinical presentation, radiographic features, and OK-432 sclerotherapy. In conclusion, repeated OK-432 sclerotherapy may be an effective treatment option in giant cervicomediastinal cystic hygroma. Pay close attention to patient's symptoms and vital signs, adjusting the OK-432 dose throughout the process., Competing Interests: The authors state no conflict of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Purpose: Sclerotherapy is frequently employed in treating lymphatic malformations (LMs), and multiple agents, practitioners and strategies exist. This review investigates the reported efficacy and safety of sclerosants in the pediatric population., Methods: Adhering to PRISMA guidelines, multiple databases were queried without linguistic or temporal restriction. Inclusion criteria were patients aged 0-18 exclusively receiving injection sclerotherapy for the treatment of LMs with follow-up data. Data abstracted included agent, dose, anatomic site and key outcome measures including complications (major/minor) and resolution rates (>95% reduction in volume). Critical appraisal was undertaken using the MINORS tool., Results: Forty-eight studies met the inclusion criteria with a mean MINORS score of 0.65 ± 0.08. Included studies yielded 886 patients, across nearly 30 years. The overall observed rate of success was 89%, with variable follow-up across publications (6 weeks - 10 years). Most reported LMs were macrocystic (82%) and had a higher resolution rate than mixed/microcytic variants (89%, 71%, 34%, p<0.01) For head/neck LMs, rates of complete regression for OK-432, bleomycin, and doxycycline were 67% ± 27% (n = 26), 91% ± 53% (n = 34) and 85% ± 16% (n = 52) respectively. Major complications were most commonly reported with OK-432, including airway compromise or subsequent operation., Conclusions: In pediatric patients treated for LM by sclerotherapy, complication rates were low. Macrocystic lesions respond well but success rates were modest at best for microcystic disease. Differences in agent utilization were noted between high and low resourced contexts; despite its lack of federal approval, OK-432 was the most reported agent. Further prospective research is warranted. LOE: 3a., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To review the effectiveness and safety of chemical ablation using ethanol or OK-432 for the treatment of TGDCs (thyroglossal duct cysts)., Methods: MEDLINE and EMBASE databases were searched up to May 29, 2020, to identify studies reporting the safety and efficacy of chemical ablation using ethanol or OK-432 for the treatment of TGDCs. The search query consisted of synonyms of thyroglossal duct cysts and ethanol or OK-432 ablation. The pooled success and complication rates were calculated using the inverse variance method to calculate weights, and pooled proportions were determined using the DerSimonian-Laird random-effects method., Results: Seven original articles including a total of 129 patients were included. The efficacy of chemical ablation was acceptable, with a pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). Repeat ethanol ablation achieved a pooled success rate of 47% (95% CI, 24-71%). The chemical ablation procedures were safe, with a pooled major complication rate of 0.9% (95% CI, 0.1-5.8%)., Conclusions: Chemical ablation using ethanol or OK-432 for the treatment of TGDCs had acceptable success and low complication rates, and repeat treatment after initial failure was also feasible. In addition, it is an inexpensive and simple procedure and could therefore be considered a first-line treatment for TGDCs., Key Points: • The efficacy of chemical ablation using ethanol or OK-432 was acceptable, with a pooled success rate of 70% (95% CI, 47-86%). The pooled success rate of ethanol ablation was superior to that of OK-432 ablation, although with equivocal statistical significance (84% vs. 51%, p = 0.055). • Repeat ethanol ablation was also feasible, with a pooled success rate of 47% (95% CI, 24-71%). • The chemical ablation procedures were safe, with a pooled major complication rate of 0.9% (95% CI, 0.1-5.8%)., (© 2021. European Society of Radiology.)

&lt;b&gt;Introduction:&lt;/b&gt; Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.&lt;br/&gt;&lt;br/&gt; &lt;b&gt;Aim:&lt;/b&gt; Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. &lt;br/&gt;&lt;br/&gt; &lt;b&gt;Material and methods:&lt;/b&gt; This study is designed as a case series with planned data collection at Tohoku Medical and Pharmaceutical University and Fukase Clinic. Five patients with recurrent thyroglossal duct cyst after surgery received this therapy between January 2014 and February 2020 on an outpatient basis, without hospitalization. OK-432 solution was injected into the lesion using an 18- or 27-gauge needle, depending on the location and size of the lesion, as well as on possible complications.&lt;br/&gt; &lt;br/&gt; &lt;b&gt;Results:&lt;/b&gt; Lesions showed marked reduction or total shrinkage in all patients, with no local scarring or deformity at the injection site. Side effects manifested as local pain at the site of injection and fever (37.5-38.5°C) observed in three patients, but the symptoms resolved within a few days.&lt;br/&gt; &lt;br/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; Since OK-432 therapy is simple, easy, safe and effective, it can be used as an alternative to surgery in the treatment of recurrent thyroglossal duct cyst after surgery.

Background: Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is currently surgical excision of the sublingual gland. Sclerotherapy with OK-432 is a well-established treatment of lymphatic malformations, but not yet thoroughly evaluated on ranulas. Objectives: To evaluate sclerotherapy of ranulas with OK-432 in a randomized double-blinded trial., Materials and Methods: 20 patients with plunging or intraoral ranula were randomized to two double-blinded injections with OK-432 or saline. Effect on the ranula and evaluation of symptoms and QOL were investigated., Results: Treatment response differed significantly between OK-432 and placebo, p  = .041(student's T-test). All patients with intraoral ranulas had a complete response, but only 1/4 of the patients with plunging ranula. The inflammatory reaction after injection with OK-432 caused a mild to moderate impact on QOL. No serious complications were observed., Conclusion: This study suggests that sclerotherapy with OK-432 in ranula is a very effective treatment for intraoral ranulas, but possibly less useful in plunging ranulas., Significance: This is a limited study, but we believe that sclerotherapy with OK-432 should be recommended as primary treatment at least for intraoral ranulas.

Objective: This study aimed to determine the benefits of sclerotherapy with OK-432 for the treatment of postoperative chronic lymphocele., Background: Postoperative chronic lymphocele formation is common and accounts for a high postoperative morbidity. Nonsurgical strategies comprise repetitive percutaneous fluid aspiration or percutaneous sclerotherapy. OK-432 has been used to treat congenital lymphatic malformations with several reports of promising results. We hypothesized that it is more beneficial than repetitive percutaneous fluid aspiration for the treatment of symptomatic lymphocele., Methods: Two cohorts of melanoma patients who developed recurrent lymphocele after lymph node dissection from January 2013 to August 2017 were compared. The first cohort was treated with repetitive percutaneous fluid aspiration (n = 20). The second cohort received OK-432 sclerotherapy (n = 20). Primary end points were overall treatment duration, number of treatment sessions, and the clinical success in both cohorts. Secondary end points were surgical site infection rate, need for additional antibiotic treatment, wound healing disorders, and the need for revision surgery., Results: Mean overall duration of treatment with sclerotherapy was significantly shorter than with repetitive aspiration (9.4 ± 7.2 vs 47.5 ± 31.9 days, P < 0.01). Mean number of sclerotherapy treatment sessions were 2.5 ± 1.2. Clinical success with OK-432 was 19 of 20, and that with repeated aspiration was 7 of 20 (χ = 15.82, P < 0.001). No surgical site infection occurred in the sclerotherapy cohort, which was significantly lower than those treated with repetitive aspiration (P < 0.03). Surgical revision was mandatory in 12 of 20 patients who were treated with repetitive aspiration, and only 1 of 20 patients in the sclerotherapy cohort., Conclusion: Sclerotherapy with OK-432 for the treatment of postoperative lymphocele is highly beneficial with a significant reduction of morbidity and the overall treatment time compared with repetitive aspiration.

Purpose of Review: Currently, there is no ideal management for orbital lymphatic malformations. Significant advances have been made since the discovery of new agents in the treatment. The purpose of this manuscript is to review the recent evidence on new sclerotherapy agents and systemic medications., Recent Findings: Traditional sclerosants are OK-432, sodium tetradecyl sulphate and ethanol. More recent developments are the use of doxycycline, bleomycin, and pingyangmycin. Sirolimus as a systemic medication has revolutionized the medical management of lymphatic malformations. Other oral drugs such as propranolol and sildenafil are controversial. Future treatment involves targeting lymphangiogenic pathways including inhibition of vascular endothelial growth factors and the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit., Summary: The development of new agents allows multimodal management either as monotherapy or combined therapy to achieve better outcomes in this difficult to manage disease.

Background: Although there are studies regarding the efficacy of OK-432 sclerotherapy on thyroglossal duct cyst (TDC), its effects on surgical procedure following this therapy have not been properly described. Objectives: The present study aimed to delineate the prognostic factors of OK-432 sclerotherapy in patients with TDC and investigate its influence on subsequent surgical procedure and the histological characteristics in patients with poor response to OK-432 sclerotherapy. Material and methods: We conducted a retrospective analysis of the medical records of 20 TDC patients treated with OK-432 sclerotherapy. Results: Of the 20 patients, OK-432 sclerotherapy was effective in 5 patients (25.0%). OK-432 showed a lower effective rate in multilocular cysts (9.1%) than in unilocular cysts (44.4%), although not significantly. Five cases were treated with surgery following OK-432 sclerotherapy. There was no significant difference in the operating time and the amount of bleeding between patients with and without OK-432 sclerotherapy. From the results of the histological examination of the cyst wall, two cases had stratified squamous epithelium and two cases showed the absence of lymphocyte infiltration. Conclusion and significance: OK-432 sclerotherapy is an acceptable initial treatment for TDC, especially in unilocular cysts, because of lack of influence on surgical procedure.

Objectives: The aim of this article was to investigate the effectiveness and underlying mechanisms of OK-432 therapy in patients with auricular hematomas., Study Design and Setting: Case series with planned data collection., Subjects and Methods: We tried this therapy in 47 patients with auricular hematoma between April 2008 and August 2018. We aspirated as much of the fluid content of each lesion as possible with a 21-gage needle. We injected OK-432 solution into the lesion with the same needle that we used for aspiration. We performed this treatment at an outpatient basis without hospitalization., Results: Disappearance and marked reduction of the lesion were observed in all patients who had this therapy, and local scarring and deformity of the auricle did not occur in any patients. As adverse effects, local pain at the injection site and fever (37-38.5°C) were observed in some cases of the patients who had this therapy. The concentrations of various cytokines in each aspirate before and after OK-432 therapy were investigated. The production of tumor necrosis factor-α, interleukin-6, interleukin-8, interferon gamma, vascular endothelial growth factor, and periostin was significantly elevated in the aspirate fluid after OK-432 therapy., Conclusion: OK-432 therapy is simple, easy, safe, effective, and can be used as a substitute for surgery in the treatment of auricular hematoma.

Aim: We assessed the long-term health-related quality of life (HRQoL) of children who received sclerotherapy for lymphatic malformations. This treatment involved injecting drugs into the blood vessels to make them shrink., Methods: Our cross-sectional study retrospectively reviewed patients who received OK-432 sclerotherapy injections at Karolinska University Hospital, Stockholm, Sweden, from 1998 to 2013. We studied 49 patients (63% female) aged 8-18 at least five years after their first injection. HRQoL was assessed with the KIDSCREEN-52 questionnaire and a study-specific questionnaire addressed disease consequences and patient satisfaction. We determined associations between HRQoL and disease and treatment and the patient's sex., Results: Overall HRQoL paralleled age-appropriate norms in the general population, but some subgroups had lower levels. Regression-based estimates showed that larger numbers of injections were negatively associated with HRQoL in the dimensions autonomy, parent relations and home life, financial resources and school environment (p = 0.01-0.03). Malformations in the head and neck area were negative predictors across dimensions and were strongest for psychological well-being (p = 0.009), parent relations and home life (p = 0.017) and school environment (p = 0.006)., Conclusion: Despite generally positive outcomes, multiple injections and malformations in the head and neck were associated with impaired HRQoL., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: The occurrence of seroma formation and long-term wound healing remain challenging complications after modified radical mastectomy. Sapylin is a drug used to reduce seroma formation and enhance wound closure, but these results remain controversial. We aimed to investigate the potential mechanism., Methods: A prospective, consecutive cohort study included 120 patients diagnosed with breast cancer who underwent modified radical mastectomy was designed. Patients were randomized into two group, using or not using OK-432 (sixty patients per group) during surgeries. Patients' drainage fluids were collected for three days after surgery. Inflammatory cytokines and chemokines were measured with ELISA assays. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells HUVEC and HFL1 cells were measured after being treated with drainage fluids., Results: Our clinic data showed that there was no statistical significance between the two groups in patient characteristics before surgery. However, the outcomes of patients in experimental group were significantly better than those in control group. In vitro studies, the results of ELISA assays showed that several cytokines, including IL-1a, IL-6, TGF-β1, bFGF and VEGF were increased in the drainage fluids treated with Sapylin. The proliferative, migratory, and angiogenic capacity of HUVEC and HFL1 cells were significantly enhanced after being treated with Sapylin group drainage fluids., Conclusion: Sapylin could stimulate the body to secrete a variety of cytokines to promote wound healing by promoting endothelial cell proliferation and migration, angiogenesis and by increasing fibroblast migration and collagen deposition., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: In advanced ovarian cancer, traditional therapy included debulking surgery and postoperative chemotherapy. We proposed immunochemotherapy (IMCT) combined with picibanil (OK-432), interleukin-2 (IL-2), and traditional platinum- and taxol-based chemotherapy as a better treatment option for advanced ovarian cancer., Methods: We retrospectively reviewed the medical records of 51 patients with advanced ovarian cancer between 2007 and 2015 at Chang Gung Memorial Hospital Linkou Medical Center, including 26 patients who were treated with OK-432, IL-2, and platinum- and taxol-based chemotherapy (IMCT group) after debulking surgery; another 25 were treated with traditional platinum- and taxol-based chemotherapy (traditional chemotherapy group) after debulking surgery. We analyzed the difference in age, follow-up period, recurrence rate, and diagnosis-to-recurrence period between the 2 groups. We also analyzed the difference in complete blood cell counts, differentiating counts, and cancer antigen 125 (CA-125) at 1 month after treatment., Results: The recurrence rate between the IMCT and traditional chemotherapy groups showed a significant difference (53.8% vs 88%; P = .0128). The diagnosis-to-recurrence duration was longer in the IMCT than in the traditional chemotherapy groups (33.21 vs 25.63 months), although no statistical significance was found ( P = .4668). In laboratory analysis at 1 month after treatment, the white blood cell, absolute neutrophil, and absolute lymphocyte counts (ALCs) were significantly higher in the IMCT group. On the other hand, CA-125 was significantly lower, and ALC was significantly higher in the nonrecurrence group., Conclusions: Combined IMCT and chemotherapy have lower recurrence rate compared to traditional chemotherapy after debulking surgery for the treatment of advanced ovarian cancer.

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., (© 2018 S. Karger AG, Basel.)

Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a. Prior vaccination with OK-432 formulated against OVA attenuated lung eosinophilic inflammation and Th2 cytokine responses that were caused by challenging with OVA through the airway. This vaccination with OK-432 augmented the ratios of IFN- γ /interleukin- (IL-) 4 cytokine and IgG2a/IgG1 antibody compared to the formulation with Th2 adjuvant aluminum hydroxide (Alum) or antigen only. The results obtained in this study lead us to propose a potential novel adjuvant for clinical use such as prophylactic vaccination for pathogens and immunotherapy in atopic diseases.

Head and neck masses can present in different pathologies that usually vary according to the age of the patient. We report five cases of benign head or neck masses occurring among patients of different ages who were managed at the Bahrain Defence Force Royal Medical Services Hospital, Ar-Rifaa, Bahrain, between 2005-2014. All of the patients were treated using the sclerotherapeutic agent OK-432. Although surgical removal is usually considered optimal treatment in the management of such cases, OK-432 appears to be a promising alternative.

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., (Copyright: © 2018 Permanyer.)

Background and Objective: 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., Methods: We retrospectively reviewed patients who underwent pleurodesis with talc or OK-432 at the University of Tokyo Hospital., Results: 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., Conclusion: Older age and underlying interstitial abnormalities on chest CT seem to be risk factors for developing ARDS after talc pleurodesis., (© 2017 Asian Pacific Society of Respirology.)

Rationale: Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular and skeletal abnormalities. The present study describes KRAS somatic mosaic mutation in a case of LNSS with lymphatic malformations (LMs)., Patient Concerns: A 4-month-old female with a clinical diagnosis of LNSS presented with infantile spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital atrial septal defect, and LMs., Diagnosis: Cervical ultrasonography revealed a 4.6 × 4.6 × 2.2cm no echo packet with clear boundary in the subcutaneous tissues of the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation was not present in the blood samples of the patient and her parents., Interventions: The patient received sclerotherapy with paicibanil (OK-432) injection for the cyst., Outcomes: Following 1 year of treatment, the patient exhibited fewer seizures. The mental and motor development was significantly improved. The patient can currently walk with assistance and speak simple words., Lessons: LNSS is a rare, congenital neurocutaneous syndrome consisting of a spectrum of abnormalities involving the skin, central nervous system, eyes, LMs and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS family of genes. Multidisciplinary evaluation and treatment is needed., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Herein, the authors aim to describe their findings of novel architectural types of lymphatic malformations (LM) and explain the relationship between these architectures and OK-432 treatment outcomes., Methods: A retrospective review was conducted of all patients diagnosed with a LM treated with OK-432 at the Vascular Anomalies Clinic at BC Children's Hospital from December 2002 to January 2012., Results: Twenty-seven patients were included in the study. Sixty percent of lesions were present by 2 years of age with the majority located in the head and neck (59%). The average number of sclerotherapy procedures was 1.4 per patient. Treatment under fluoroscopic guidance revealed 3 new LM architectures: open-cell microcystic, closed-cell microcystic, and lymphatic channel. Response to treatment was complete or good for 14/19 macrocystic and for 1/2 mixed lesions. Open-cell microcystic LMs gave a complete or good response for 3/3, which was attributed to OK-432 freely communicating between cysts. Closed-cell microcystic LM had localized cysts that did not allow OK-432 to freely communicate and were associated with partial responses, 2/2. The lymphatic channel had a partial response. There were 2 minor complications and 1 instance of recurrence., Conclusions: The identification of 3 new LM architectures expands the current accepted classification to include: open-cell microcystic, closed-cell microcystic, and lymphatic channels. The majority of complete responses to OK-432 were found with macrocystic lesions. Open-cell microcystic lesions respond better to OK-432 than closed-cell microcystic lesions, and lymphatic channels may respond to OK-432. These key architecture-response relationships have direct clinical implications for treatment with OK-432 sclerotherapy.

Lymphatic malformations are rare slow-flow vascular malformations, with high tendency to appear in the head and neck region. The treatment of these lesions ranges from follow-up to sclerosing agent injection to surgical excision. The authors present a case of a new born with large extensive lingual and submandibular lymphatic malformation, for which the patient underwent tracheostomy and gastrostomy insertion. He was then treated successfully with sclerosing agent injections followed by surgical excision, with 7 years follow-up. The second case presented is a two and a half baby with large lingual lymphatic malformation, treated successfully with doxycycline injections followed by intraoral excision of the lesion. Pathology of the excised lesion is then demonstrated, which shows for the first time the different layers affected by the sclerosing agent.

Background: Congenital 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 Presentation: Here 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., Conclusions: Contrast 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.

Purpose/aim: Modified radical mastectomy is the standard surgery for breast cancer in developing countries. However, seroma formation regarded as the most frequent postoperative complication limits the therapeutic benefit of mastectomy and axillary surgery. The purpose of this study was to evaluate the efficacy of OK-432 in reducing seroma formation after axillary dissection., Methods: This prospective cohort study included 80 patients with advanced breast cancer who underwent modified radical mastectomy. Patients were randomized into two groups, which differed with the OK-432 administration. N = 40 patients per group were treated with either OK-432 plus closed suction drainage or drainage-only., Result: In comparison with the drainage-only group, we found that patients in the OK-432 group had a lower drainage volume (p = .030) and a shorter duration of axillary drainage (p < .01). Besides, the use of OK-432 could reduce the incidence of seroma formation (p < .01) and the volume of seroma (p = .040). There were also significant differences in reducing the chance of evacuative punctures (p = .036) and the healing time (p < .01) between control and OK-432 group., Conclusion: OK-432 not only shortened the suction drainage duration, but also significantly reduced seroma formation as well as the needs for aspiration punctures after modified radical mastectomy.

Purpose: 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., Patients and Methods: 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., Results: A total of 23 patients received OK-432 injection therapy for an intraoral ranula. The mean lesion size was 19.96 mm. The mean aspiration volume was 2.14 mL. 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 17.38 mm and 1.40 mL, respectively. The lesion length and aspiration volume of the PR/NR group was 29.20 mm and 4.80 mL, respectively. The PR/NR group lesions were significantly larger than the CR group lesions., Conclusions: 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., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA., Methods: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay., Results: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state., Conclusions: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity.

Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.

Background: The choice of an optimal sclerosant for pleurodesis for malignant pleural effusion remains controversial. This retrospective clinical study compared the efficacy and safety of two sclerosants; talc slurry (talc-s) and OK-432., Methods: We compared the characteristics, 30/90-day success rates, and adverse events in patients with lung adenocarcinoma who underwent pleurodesis by using either OK-432 or talc-s. Propensity score matching was used to compare the two scelrosants., Results: Ninety-four patients (mean age=71.6±9.6 years) were included in this retrospective study, of whom 64 received OK-432 and 30 received talc-s. Seventy-three patients (77.6%) were initially diagnosed with clinical stage IV lung cancer, with a 28.7% epidermal growth factor receptor mutation frequency. The propensity score-matched cohort included 26 patients from each group. The 30-day success rates for OK-432 and talc-s were 80.7% and 76.9%, respectively (odds ratio: 1.26, 95% confidence interval: 0.33-4.77, p=0.73). Neither the overall incidence of adverse events nor the 90-day success rates differed significantly. Multivariate logistic regression revealed that the predictors of 30-day success were lower drainage volume on the previous day, particularly <250mL/day, the presence of full lung expansion, and pre-therapy with an epidermal growth factor receptor-tyrosine kinase inhibitor. The median post-pleurodesis survival time was 6.9 months, which was not significantly different between the study groups., Conclusions: Propensity score-matched analyses showed that pleurodesis using OK-432 and talc-s demonstrated comparable efficacy and safety profiles in patients with lung adenocarcinoma. This indicated that OK-432 could be a viable alternative to talc-s in this procedure., (Copyright © 2016. Published by Elsevier B.V.)

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., (Copyright © 2013. Published by Elsevier B.V.)

Background: OK-432 has been used as a cancer treatment for 40 years, and the immunostimulatory effects of OK-432 therapy have been intensely investigated in Japan. Recently, it has received attention as a possible booster for cancer vaccine treatments. Our previous meta-analysis based on summary measures revealed a significant improvement in the survival of patients with curatively resected gastric cancer. However, it is impossible to exclude the possibility of bias due to several prognostic factors., Methods: We collected individual data for patients with stage III or stage IV gastric cancer after curative resection from 14 trials that were identified in a previous meta-analysis. Immunochemotherapy with OK-432 was compared with treatment with standard chemotherapy on an intention-to-treat basis. The primary end point was overall survival. Stratified survival analyses were performed with the trial as the stratification factor. Subgroup analyses were also performed according to the potential prognostic factors, which included pathological factors, splenectomy, and delayed-type hypersensitivity., Results: There were 796 and 726 patients in the OK-432 and control groups, respectively. The median overall survival was 42.6 months for the OK-432 group and 32.3 months for the control group. The overall hazard ratio was 0.88 (95 % confidence interval 0.77-1.00, p = 0.050). No factor showed a statistically significant interaction in the subgroup analyses., Conclusions: The results suggest that immunochemotherapy treatment with OK-432 could have a borderline significant effect for patients with stage III or stage IV gastric cancer after curative resection.

OK-432 is an immunomodulator that has been reported to be efficacious as an injection therapy for cervical lymphomas and ranulas. We performed OK-432 injection therapy to treat a cystadenocarcinoma of the parotid gland in a 72-year-old man. The 50 × 46-mm tumor was located in the deep lobe of the gland. The tumor had compressed the glossopharyngeal, vagus, and hypoglossal nerves, causing neurally mediated syncope, hoarseness, dysphagia, and dysarthria. A concentration of 5 KE/2 ml of OK-432 was injected. Within 2 months, the cyst had disappeared; no recurrence was apparent during 59 months of follow-up. To the best of our knowledge, no previous report has described injection of OK-432 for malignant cystic disease. We describe the injection method, injection dose, and postinjection course in the hope that this information will prove useful for future applications against malignant cystic disease.

Gorham's disease (GD) is a rare and intractable disease characterized by marked progression of osteolysis associated with lymphangioma and/or hemangioma. Here, we describe a case of GD of the proximal tibia occurring in a 10-year-old boy. Although we could not correctly diagnose it at first, we finally diagnosed him as having GD. Progression of osteolysis of the tibia stopped 3 months after the local administration of OK-432. Thereafter, the huge bone defect with varus and extension deformity was reconstructed successfully by distraction osteogenesis using the Ilizarov method. The present case suggests that local administration of OK-432, followed by distraction osteogenesis is a treatment option for GD.

In the investigation 97 children were included, suffering cystic lymphatic malformations, who were treated in 2011 — 2016 yrs. Lymphatic malformations were classified, depending on the cysts size: macrocystic, microcystic, and the mixed. Sclerotherapy, using biological preparation ОК—432, was conducted in 80 (82.5%) children, surgical excision of lymphatic malformations — in 10 (10.3%), the combined treatment — in 7 (7.2%).

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., Competing Interests: The authors have no funding and conflicts of interest to disclose.

Aim: Sclerotherapy is the primary treatment for lymphatic malformations. The aim of this study was to evaluate the long-term outcome in patients with lymphatic malformations treated with the immunostimulant OK-432 as a sclerosant., Methods: Between 1998 and 2013, we enrolled 131 of 138 eligible patients treated with OK-432 for lymphatic malformations in a retrospective study. The malformations were categorised according to the International Society for the Study of Vascular Anomalies. The outcome was assessed with a clinical examination and a questionnaire., Results: The lymphatic malformations were localised to the head/neck (60%), the trunk (20%) and the extremities (6%) or involved with more than one region (14%). Patients with microcystic (10%), macrocystic (21%) and mixed lymphatic malformations (69%) underwent a median number of three, two and two injection treatments, respectively. The median age at the first injection was 3.4 years. Good or excellent clinical outcomes were seen in 70% of the patients. The number of injections, previous treatment and lesion localisation, but not time to follow-up and cyst size, predicted the clinical outcome., Conclusion: OK-432 treatment resulted in a successful outcome in 70% of patients with lymphatic malformations. The long-term outcome was comparable to the short-term outcome., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Purpose of Review: To review the literature on lymphatic malformations and to provide current opinion about the management of these lesions., Recent Findings: Current treatment options include nonoperative management, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New therapies are emerging, including sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management centers on the patient's quality of life., Summary: Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, in addition to knowledge gained from clinical practice. A patient-centered approach should guide timing and modality of treatment. Continued study of lymphatic malformations will increase and solidify a treatment algorithm for these complicated lesions.

Background: Primary fetal hydrothorax (PFHT) is an uncommon condition with an estimated prevalence of 1 in 10,000/15,000 pregnancies. Therapeutic interventions include thoracocentesis, thoraco-amniotic shunting (TAS), and pleurodesis using OK-432., Methods: A review of the literature was performed to identify all cases of PFHT treated with TAS and OK-432. All cases of PFHT referred to the Fetal Maternal Unit at Royal Prince Alfred Hospital between 2002 and 2012 were retrospectively reviewed. In the cohort of fetuses treated with OK-432, the main perinatal outcomes evaluated were termination of pregnancy, live birth, neonatal death, and fetal death in utero. Secondary outcomes included gestational age (GA) at diagnosis, GA at treatment, GA at resolution, birth weight, and GA at birth. The development of the children was screened using the Ages and Stages Questionnaires, Version 3 (ASQ-3, 2009)., Results: Primary hydrothorax was diagnosed in 31 fetuses, of which 14 had treatment with OK-432. One pregnancy terminated after treatment with OK-432. Survival was 85% (11/13): 100% in fetuses treated with OK-432 without hydrops, and 78% in those treated with hydrops. This compares well to the cases of TAS in the literature with an average survival of 63%: 85% in fetuses without hydrops and 55% with hydrops. The mean GA at birth was 36(+4) weeks and mean birth weight 3,007 g. Eight of the 9 children screened with ASQ-3 scored well within the normal range., Conclusion: OK-432 appears to be a valid treatment option in fetuses with PFHT, particularly in those diagnosed at early GAs., (© 2014 S. Karger AG, Basel.)

Purpose of Review: Ranula is extravasation mucocele arising from the sublingual gland, influencing the swallowing or eating; this review focuses on the most recent literature pertaining to pediatric ranulas and aims to comprehensively describe the methods of diagnosis and management approaches., Recent Findings: Ranulas consist of intraoral ranula and plunging ranula, which are frequently misdiagnosed, so it is vital for the differential diagnosis of pediatric ranulas to depend on the clinical examination, imaging and fine-needle aspiration cytology. Pediatric patients should first be observed for 6 months before other treatments. OK-432 could activate inflammatory reaction to induce shrinkage of pediatric ranulas. Marsupialization, incision with drainage and ranula excision alone, are associated with a high rate of recurrence, even marsupialization with packing and modified micromarsupialization should be prudently applied for primary treatment of intraoral ranula. Laser excision is considered an alternative treatment for intraoral ranula of pediatric patients because of low recurrence rates and surgical complications. Recently, sublingual gland with or without ranula excision is a reasonable and suitable choice for radical treatment in pediatric patients., Summary: The principal goal of pediatric ranula management is radical sublingual gland excision, sealing the mucus extravasates and lowest complications.

Chylothorax, a relatively rare complication of thoracic surgery, mostly occurs on the right side. We present a 16-year-old male who received thoracoscopic surgery for left spontaneous pneumothorax. Chylothorax developed on the postoperative 2(nd) day and resolved after diet control on the 4(th) day. Unfortunately, chylothorax recurred 2 weeks later. Chest drainage and nil per os with total parental nutrition were given but in vain. Thereafter, chemical pleurodesis with OK-432 was performed. Chylothorax resolved on the next day. The relevant literature is reviewed and possible pathogenesis clarified., (Copyright © 2014. Published by Elsevier Taiwan.)

Objective: Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with OK-432, bleomycin and surgery, and a combination of the three modalities., Methods: We performed a retrospective, cross-sectional study including patients treated from 1998 to 2011. The effects on macrocystic lymphangiomas and adverse reactions were evaluated. Twenty-nine children with cystic lymphangiomas without any previous treatment were included. Under general anesthesia, patients given sclerosing agents underwent puncture of the lesion (guided by ultrasound when necessary) and complete aspiration of the intralesional liquid. The patients were evaluated with ultrasound and clinical examinations for a maximum follow-up time of 4 years., Results: The proportions of patients considered cured after the first therapeutic approach were 44% in the surgery group, 29% in the bleomycin group and 31% in the OK-432 group. These proportions were not significantly different. Sequential treatment increased the rates of curative results to 71%, 74% and 44%, respectively, after the final treatment, which in our case was approximately 1.5 applications per patient., Conclusion: The results of this study indicate that most patients with cystic lymphangiomas do not show complete resolution after the initial therapy, regardless of whether the therapy is surgical or involves the use of sclerosing agents. To achieve complete resolution of the lesions, either multiple operations or a combination of surgery and sclerotherapy must be used and should be tailored to the characteristics of each patient.

Background: No previous study to the best of our knowledge has examined the multiple factors related to the outcome of OK-432 sclerotherapy of lymphatic malformations., Objective: This study aimed to assess factors related to the successful outcome of OK-432 sclerotherapy for lymphatic malformations in the head and neck region., Materials and Methods: During a 6-year period, OK-432 sclerotherapy was performed in 26 patients with lymphatic malformations. Several factors related to the efficacy of OK-432 sclerotherapy were evaluated, including the type (macrocystic or microcystic), the maximum lesion diameter, amount and hemorrhagic cytology of the aspirate, degree of aspiration, injected dose of OK-432 and post-therapy inflammation-related symptom. In all cases, ultrasound (US) follow-up was performed., Results: Of the 26 cases, 13 (50%) showed successful elimination of the lymphatic malformations in the follow-up US after the initial session, and all successful cases were of the macrocystic type. The type of lymphatic malformation and the success of OK-432 sclerotherapy were significantly related (P = 0.0149). Of the 16 cases of complete aspiration, 11 (68.8%) showed a successful outcome. Further, of the 17 cases with inflammation-related symptom, 13 (76.5%) showed a successful outcome. While the degree of aspiration and presence of inflammation-related symptom showed a significant relationship with the success of OK-432 sclerotherapy (P < 0.05), no other factors showed a significant relationship., Conclusion: The study results suggest that the macrocystic type and complete aspiration of cystic contents were important factors for the success of OK-432 sclerotherapy of lymphatic malformations, and that inflammation-related symptom was a predictor of a successful outcome.

Orbital lymphangiomas are mostly congenital, apparent vascular space-occupying lesions, which can lead to disfiguring swelling of the periorbital soft tissues, ocular motility disorders, optic nerve compression and keratopathy. The treatment is challenging because the disease is principally incurable. Lymphangiomatous tissue can be surgically partially reduced or treated by intralesional injection of various sclerosants. In this review we report the successful use of OK-432 for destruction of a macrocystic orbital lymphangioma.

Background: Sclerotherapy with OK-432 is recommended as a first-line treatment for lymphatic malformations. However, 40% of patients show poor response, defined by involution to <50% of the original size. It has been suggested that the OK-432 effect is highly dependent on the Toll-like receptor (TLR) 4-dependent expression of TLR7 in antigen-presenting cells. We hypothesized that the ability for TLR expression in monocytes after treatment with the TLR4-ligand lipopolysaccharide (LPS) can be used to predict successful OK-432 treatment., Methods: Blood was taken from children with low responder (LR, n = 6) and high responder (HR, n = 5) of previous OK-432 treatment. Monocytes were stimulated with LPS for 20 h. TLR expression was analyzed with fluorescence-activated cell sorting (mean fluorescence intensity). The level of significance was P ≤ 0.05., Results: The mean age of patients in the HR group was 1.4 ± 0.9 y and in the LR group 2.8 ± 2.9 y (P = 0.31). The mean TLR4 upregulation after LPS stimulation in the HR group was significantly higher than in the LR group (factor 3.6 versus factor 1 compared with nonstimulated controls; P = 0.037). The mean TLR7 expression did not show significant differences between the groups., Conclusions: Dynamic TLR4 expression represents most probably a predictive parameter for the treatment of lymphatic malformations with OK-432 and should be further investigated., (Copyright © 2014 Elsevier Inc. All rights reserved.)