Radiofrequency hyperthermia enhances the effect of OK-432 for Hepatocellular carcinoma by activating of TLR4-cGAS-STING pathway.

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.

Effectiveness of pleurodesis for postoperative air leaks after lung resection.

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.

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.

Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation.

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. MATERIALS AND 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-ß 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. CONCLUSION: 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.

Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND AND AIMS: 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). APPROACH AND 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. AVAILABILITY OF DATA AND MATERIAL: The data of this study are available from the corresponding author on reasonable request.

Efficacy of OK-432 sclerotherapy for different types of lymphangiomas: a review and meta-analysis.

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. 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.

[Interstitial Lung Disease after OK-432 Pleurodesis for Malignant Pleural Effusion in Breast Cancer-A Case Report].

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.

Intraoperative OK-432 pleurodesis for preventing recurrence of primary spontaneous pneumothorax in children and adolescents: a single-center experience.

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.

OK-432 Sclerotherapy of Giant Cervicomediastinal Cystic Hygroma.

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.

[Algorithm of Therapy for Spontaneous Pneumothorax].

The initial treatment for the patient with primary or secondary spontaneous pneumothorax occupying less than 15% of the hemithorax is observation. And then the treatment with primary spontaneous pneumothorax greater than 15% of the volume of hemithorax is a simple thoracoscopic aspiration. However, the treatment with secondary spontaneous pneumothorax greater than 15% of the volume of hemithorax is tube thoracotomy. Conservative treatment for continuous air leakage with secondary spontaneous pneumothorax is instillation of a sclerosing agent( small amount of picibanil 3 KE). Surgical treatment for continuous air leakage with secondary spontaneous pneumothorax due to severe idiopathic pulmonary fibrosis (IPF) is intractable. We have experienced three cases in which surgical treatment is difficult in secondary spontaneous pneumothorax with underlying lung diseases. The first cases are a pneumothorax with a giant bulla or severe lung emphysema. Second cases are a pneumothorax with a fragile lung. Third cases are a pneumothorax with a hardened lung. We need devised surgical approaches to these cases.

Generation of Leukaemia-Derived Dendritic Cells (DCleu) to Improve Anti-Leukaemic Activity in AML: Selection of the Most Efficient Response Modifier Combinations.

Dendritic cells (DC) and leukaemia derived DC (DCleu) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DCleu-generating protocols. With respect to future clinical applications though, DC/DCleu-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DCleu-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DCleu from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E1 (PGE1), prostaglandin-E2 (PGE2) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DCleu using refined classification and/or ranking systems; DC/DCleu were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DCleu from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE2) and -M (GM-CSF + PGE1) as the most efficient kits in generating (mature) DC/DCleu, which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DCleu-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DCleu-based immunotherapy of AML into clinical application.

Effects of Liposome-Entrapped Muramyl Tripeptide Phosphatidylethanolamine (L-MTP-PE) on the Tumor Growth and Survival of Mice Bearing Syngeneic Tumor in Combination with a Chemotherapeutic or Immunomodulatory Agent.

Antitumor activities of L-MTP-PE (Liposome entrapped myuramyl tripeptide phosphatidylethanolamine) in the combination treatment with chemo- or immune-therapeutic antitumor agents against various syngeneic tumors were tested.Against Meth A fibrosarcoma solid tumor system, L-MTP-PE showed slight but statistically significant elongation of survival days against 5-FU monotherapy in spite of its non-effect on tumor growth, when combined with 5-FU. Against liver metastasis model of M5076 carcinoma, L-MTP-PE showed a tendency of elongation of survival days by its single drug treatment, however, elongation with statistical significance was observed in the combination treatment with 5-FU in comparison with control group.These data suggest that L-MTP-PE seems to elongate the survival days of the solid tumor bearing mice and the liver metastasis model basically due to its saving effect on chemotherapeutic drug-induced immunosuppression. In the combination with an immunotherapeutic agent in mice, TNF production induced by another biological response modifier OK-432 was potentiated when primed with L-MTP-PE. L-MTP-PE also potentiate the antitumor effect of OK-432 possibly through the enhanced production of TNF-α. Combination of L-MTP-PE and OK-432 is considered to be a candidate for a new treatment model for cancer.

Sclerosing agents in the management of lymphatic malformations in children: A systematic review.

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 ±â€¯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.

Chemical ablation using ethanol or OK-432 for the treatment of thyroglossal duct cysts: a systematic review and meta-analysis.

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%).

Sclerotherapy of ranulas with OK-432 - a prospective, randomized, double-blinded placebo-controlled study.

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.

Sclerotherapy for Benign Cystic Lesions of the Head and Neck: Systematic Review of 474 Cases.

OBJECTIVE: The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck. DATA SOURCES: PubMed/MEDLINE, Cochrane Library, and Embase. REVIEW METHODS: The PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta-analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty-two studies met criteria for inclusion. RESULTS: A total of 474 cases of sclerotherapy were reviewed. Agents comprised OK-432, ethanol, doxycycline, tetracycline, and bleomycin. Lesions in the analysis were ranula, thyroglossal duct cyst, branchial cleft cyst, benign lymphoepithelial cyst, parotid cyst, thoracic duct cyst, and unspecified lateral neck cyst. A total of 287 patients (60.5%) had a complete response; 132 (27.9%) had a partial response; and 55 (11.6%) had no response. OK-432 was the most widely utilized agent, with a higher rate of complete response than that of ethanol (62.0% vs 39.4%, P = .015). Fifty-three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively. CONCLUSION: Sclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.

OK-432 treatment of pediatric patients with recurrent thyroglossal duct cyst after surgery.

<b>Introduction:</b> Recurrent thyroglossal duct cyst after surgery is not a rare condition and first-line treatment has not been established yet.<br/><br/> <b>Aim:</b> Evaluation of outcomes and complications of OK-432 treatment in patients with recurrent thyroglossal duct cyst after surgery. <br/><br/> <b>Material and methods:</b> 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.<br/> <br/> <b>Results:</b> 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.<br/> <br/> <b>Conclusions:</b> 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.

Evaluation of pleural lesions after pleurodesis with OK-432 by fluorodeoxyglucose-positron emission tomography/CT.

OBJECTIVE: This study aimed to determine changes in FDG-PET/CT after pleurodesis with OK-432 and to investigate differences in the changes between non-malignant and malignant lesions. METHODS: Study participants were 17 patients with a history of malignant chest disease who underwent FDG-PET/CT after pleurodesis using OK-432 and in whom pleural lesions were determined to be non-malignant (n = 8) or malignant (n = 9). FDG uptake (SUVmax) was counted on all pleural lesions. CT findings (CT attenuation, shape) of pleural lesions with increased FDG uptake were evaluated. RESULTS: The number of patients with increased FDG uptake in the pleura differed significantly between the non-malignant group (3/8) and malignant group (9/9) (p < 0.01) The mean SUVmax of non-malignant lesions with increased FDG uptake was 2.3 ± 0.7 vs. 6.2 ± 2.2 in malignant lesions, for a significant difference (p < 0.01). The mean CT attenuation of lesions was 36 ± 11 HU in the non-malignant group and 34 ± 14 HU in the malignant group, a difference that was not significant (p = 0.91). There was a significant difference in nodular and linear shapes between non-malignant and malignant lesions (p < 0.01). All non-malignant lesions were linear. CONCLUSIONS: Positive FDG uptake was shown in non-malignant pleural lesions as well as in malignant pleural lesions after pleurodesis using OK-432. Combined analysis of FDG accumulation and CT morphology is helpful to distinguish between benign and malignant lesions.

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

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

Treatment of bronchial fistula after extraplural pneumonectomy using flexible bronchoscopy with the administration of OK432, fibroblast growth factor basic and fibrin glue sealant.

Treatment options for bronchial fistula (BF) after pneumonectomy are often limited and carry significant morbidity and mortality. The patient underwent right extrapleural pneumonectomy for malignant pleural mesothelioma had BF without macroscopic fistula found by bronchography. We treated this minor BF using bronchoscopy with the administration of OK-432, fibroblast growth factor basic, and fibrin glue sealant. Two weeks after this treatment, we confirmed the improvement of the fistula by bronchography. Bronchoscopic therapy for BF was useful for a small, early fistula without infection.