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.

BACKGROUND: Pleurodesis is often performed for air leaks; however, the ideal materials and timing of the procedure remain controversial. We investigated the efficacy of pleurodesis using different materials and timing.
METHODS: We retrospectively reviewed 913 consecutive patients who underwent segmentectomy or lobectomy for non-small cell lung cancer between 2014 and 2021. Pleurodesis efficacy was assessed on the day of chest tube removal.
RESULTS: Eighty-six patients (9%) underwent pleurodesis for postoperative air leaks. Pleurodesis was performed on a median of postoperative day (POD) 5. Talc was the most frequently used material (n = 52, 60%), followed by autologous blood patches (n = 20, 23%), OK-432 (n = 12, 14%), and others (n = 2, 2%). No difference existed in the number of days from initial pleurodesis to chest tube removal among the three groups (talc, 3 days; autologous blood patch, 3 days; OK-432, 2 days; P = 0.55). No difference in patient background, except for sex, was observed between patients who underwent pleurodesis within 4 PODs and those who underwent pleurodesis on POD 5 or later. Drainage time was significantly shorter in patients who underwent pleurodesis within 4 PODs (median, 7 vs. 9 days; P = 0.004).
CONCLUSIONS: The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required.

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.

OBJECTIVE: To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism.
METHODS: The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo.
RESULTS: LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-β in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor.
CONCLUSIONS: The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.

OBJECTIVE: 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.

OBJECTIVE: Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC).
RESULTS: The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1-6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups.
CONCLUSIONS: The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs.
UNASSIGNED: The data of this study are available from the corresponding author on reasonable request.

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 (I2=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.
CONCLUSIONS: 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.

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).
CONCLUSIONS: 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.
METHODS: Retrospective review, therapeutic study, Level III.

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.