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Background/aim: Tracheobronchial adenoid cystic carcinoma (ACC) is a rare type of malignancy. Although complete resection is standard treatment for localized ACC, treatment for unresectable ACC has not been established. It is unclear whether concurrent chemoradiotherapy (CCRT) followed by immune checkpoint inhibitor (ICI) therapy is effective for ACC., Case Report: A 49-year-old man was admitted to our hospital for the treatment of dyspnea and thickening of the bronchial wall from the tracheal carina to the left main bronchus, as observed on a CT scan. Systemic examinations and transbronchial biopsy led to a diagnosis of locally advanced ACC. Although radiotherapy and chemotherapy are not regarded as very sensitive for ACC, a favorable response was obtained with CCRT. Following CCRT, he received ICI therapy with durvalumab for 1 year. The patient has remained in a stable condition 18 months after therapy, with no recurrence., Conclusion: ICI after CCRT might be a promising treatment option for unresectable tracheobronchial ACC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Low-grade fibromyxoid sarcoma (LGFMS) is a rare mesenchymal tumor that primarily arises in the limbs and trunk of young adults, and rarely in the thoracic cavity. An 84-year-old Japanese woman presented with a right intrathoracic mass which was 8 cm in size. CT-guided needle biopsy did not provide a definitive diagnosis. Perioperatively, a mass was found in the right lower lobe of the lung and was suspected to have invaded the chest wall at the sixth-eighth ribs. A right lower lobectomy and combined chest wall resection were performed. Microscopic examination revealed that the tumor was a low-grade spindle cell tumor originating from the pleura demonstrating focal invasion of the lung. The tumor exhibited positivity for MUC4, and FUS gene translocation was confirmed through fluorescence in situ hybridization. Unfortunately, 10 months postoperatively, tumor recurrence was noted as peritoneal dissemination, and the patient passed away 13 months postoperatively. Although LGFMS may be diagnosed histologically as a low-grade tumor by needle biopsy, in this case, it was highly malignant. Postoperative long-term regular medical follow-up is recommended considering the highly malignant nature of the tumor and the high risk of local recurrence and pulmonary metastasis., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: Ewing's sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing's sarcoma) caused by chromosomal translocations have been collectively termed Ewing's sarcoma family of tumors. We report a rare case of primary adrenal Ewing's sarcoma family of tumors with tumor thrombus., Case Presentation: A 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively., Conclusion: Radical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing's sarcoma family of tumors., (© 2023. The Author(s).)

A 74-year-old Japanese woman, who had been previously diagnosed as ocular myasthenia gravis (MG), presented to our hospital complaining of dropped head and increased fatiguability while eating. The edrophonium test was positive and decremental response was recorded on repetitive nerve stimulation. Her clinical presentation was compatible with generalized MG, and anti-AChR, Kv1.4 and titin antibodies turned out positive. Contrast enhanced CT scan showed no tumorous lesion such as thymoma. We initiated her treatment with a minimum dose of oral prednisolone. However, her condition got worse even after intravenous immune globulin and experienced myasthenic crisis twice, the former of which led to cardiopulmonary arrest. As she did not respond to traditional treatments, we determined to perform extended thymectomy. The histopathology showed atrophic change but her condition rapidly improved in several days after the operation, and soon she was weaned off the ventilator. Shortly thereafter her symptoms disappeared, followed by the titers of the antibodies above found all markedly decreased. It remains unclear how the atrophic thymus acted on the pathogenesis of refractory generalized MG.

Background: Lobectomy, or the removal of a lobe of the lung, is the most commonly performed lung cancer surgery. One of the most severe postoperative complications is a bronchial stump fistula, which often occurs following a right lower lobectomy. During lymph node dissection, the bronchial arteries, which supply blood to the bronchus, are cut. Subsequently, reduced blood supply to the bronchus may result in bronchofistula. We investigated the relationship between the level of the surgical ligation of the bronchial arteries and the decrease in blood flow at the bronchial stump during a right lower lobectomy. This study aimed to clarify the relationship between the anatomical amputation level of the bronchial artery and the decrease in tissue oxygen saturation at the bronchial stump, allowing us to identify a surgical procedure that reduces the risk of a bronchopleural fistula following pulmonary lobectomy and an appropriate bronchial artery amputation site that could be used in future lobectomies., Methods: We developed a new system (micro-tissue oxygen saturation) that enabled the semi-quantification of the oxygen saturation of thin tissues in pinpoint during video-assisted thoracic surgery. Changes in the blood flow at the bronchial stump were examined during lymph node dissection and bronchial artery amputation using a biological pig lobectomy model., Results: The regional oxygen saturation level at the bronchial wall was 95.5%±1.0% in normal conditions. A gradual decrease in regional oxygen saturation was observed, as the cutting point of the bronchial artery was moved higher. When the bronchial artery coursing into the middle lobe bronchus was preserved, the blood flow in the bronchus was preserved at 82.8%±1.3%. When the branches of the bronchial arteries running both inside and outside of the intermediate bronchial trunk were cut at high positions, regional oxygen saturation level decreased to 55.7%±1.2%., Conclusions: The preservation of at least one bronchial artery at the level of the middle lobe bronchus minimizes the reduction of tissue oxygen saturation at the lower lobe bronchial stump. The ligation of bronchial arteries at a higher position results in desaturation <60%, which may increase the risk of bronchial stump fistula., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-1057). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: For the minimally invasive excision of small-sized pulmonary nodules, bronchoscopic markings are increasingly being performed owing to advancements in video-assisted thoracic surgery (VATS). Hybrid operating room equipment is utilized for bronchoscopic VATS markings. We aimed to compare the marking accuracy between bronchoscopic VATS and other marking techniques such as computed tomography-guided percutaneous marking and conventional X-ray fluoroscopy-guided bronchoscopic marking., Methods: Patients with small-sized pulmonary nodules scheduled to undergo VATS were enrolled in the study. A mixture of 50 to 100 µL of diluted indocyanine green and iopamidol was injected adjacent to the pulmonary nodules as a VATS marker. Patients receiving each of the three image-guided techniques were categorized into group A (computed tomography-guided percutaneous injection), group B (X-ray fluoroscopy-guided virtual bronchoscopy-assisted bronchoscope injection), and group C (cone-beam computed tomography and augmented fluoroscopy-guided virtual bronchoscope-assisted bronchoscopic injection in the hybrid operating room). VATS marking accuracy and procedural complications were compared among the three groups., Results: In total, 61 patients with 73 pulmonary nodules were eligible for analysis. VATS marking was successful for 15/16 nodules in group A, 28/30 nodules in group B, and 25/27 nodules in group C. Marking accuracy was 5.75±4.59, 15.00±14.02, and 6.05±6.11 (mm), respectively. Multiple markings were successful in 0/1 (0%), 5/6 (83.3%), and 5/5 (100.0%) nodules in groups A, B, and C, respectively. A small pneumothorax occurred in 3/15 (20.0%) patients in group A., Conclusions: The cone-beam computed tomography and augmented fluoroscopy-guided bronchoscopic approach performed in a hybrid operating room is accurate and equivalent to the computed tomography-guided percutaneous approach, and it enables the VATS marking of multiple pulmonary nodules without causing a secondary pneumothorax., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-781). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: To determine the appropriate amount of indocyanine green for bronchial insufflation., Methods: We enrolled 20 consecutive patients scheduled for anatomical segmentectomy in the Kochi Medical School Hospital. After inducing general anesthesia, 6 to 60 mL of 200-fold-diluted indocyanine green (0.0125 mg/mL) was insufflated into the subsegmental bronchi in the targeted pulmonary segmental bronchus. The volume of the targeted pulmonary segments was calculated using preoperative computed tomography. Fluorescence spread in the segmental alveoli was visualized using a dedicated near-infrared thoracoscope., Results: The targeted segment was uniformly visualized by indocyanine green fluorescence in 16/20 (80.0%) cases after insufflating indocyanine green. A receiver operating characteristic curve indicated that the area under the curve was 0.984; the optimal cut-off volume of diluted indocyanine green for insufflation was 8.91% of the calculated targeted pulmonary segment volume., Conclusions: The setting for indocyanine green insufflation was optimized for near-infrared fluorescence image-guided anatomical segmentectomy. By injecting the correct amount of indocyanine green, fluorescence-guided anatomical segmentation may be performed more appropriately.

Background: AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC)., Methods: Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed., Results: The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p = 0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p = 0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma., Conclusion: Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

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 (SUV max ) 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 SUV max 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.

Background: In clinical practice, various devices are implanted into the body for medical reasons. As X-ray fluoroscopy is necessary to visualize medical devices implanted into the body, the development of a less-invasive visualization method is highly desired. This study aimed to investigate the clinical applicability of our novel solid material that emits near-infrared fluorescence., Methods: We developed a solid resin material that emits near-infrared fluorescence. This material incorporates a near-infrared fluorescent pigment, with quantum yield ≥ 20 times than that of indocyanine green. It can be sterilized for medical treatment. This resin material is designed to be molded into a catheter and inserted into the body with an endoscope clip. In this preclinical experiment using a swine model, the resin material was embedded into the body of the swine and visualized with a near-infrared fluorescence camera system., Results: Endoscopic clips were placed in the mucosa of the stomach, esophagus, and large intestine, and the indwelling ureteral catheters were successfully visualized by near-infrared fluorescence laparoscopy., Conclusions: We confirmed the tissue permeability of the fluorescence emitted by our novel near-infrared fluorescent material and the possibility of its clinical application. This material may allow visualization of devices embedded in the body.

We describe a treatment strategy for an aberrant arterial aneurysm associated with pulmonary sequestration. A 58-year-old man with impending aberrant arterial aneurysm rupture underwent a 2-stage surgery that included an emergency thoracic endovascular aortic repair (TEVAR) of the descending aorta to occlude the origin of the aberrant artery, followed by lobectomy. TEVAR can lead to faster occlusion of the aneurysm and can avoid operative risk of aneurysm rupture during lobectomy. The aberrant artery was broad where it branched off the aorta and had a short neck, rendering primary ligation or stump-forming unsuitable. Pathological findings revealed the fragility of the aberrant artery; thus, its root was prone to breakdown of the stump after simple aneurysmectomy. Furthermore, TEVAR may reduce graft infection during lobectomy in the second surgery. The 2-stage surgery may be useful for aberrant aneurysms complicated by pulmonary sequestration., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: We report the first case, to the best of our knowledge, of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy (KM-CART). The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to investigate anticancer drug susceptibility., Case Summary: A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites; more than 4000 mL of ascitic fluid was removed, filtered, and concentrated using KM-CART, and the cell-free ascitic fluid was reinfused into the patient to improve quality of life. Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine. Treatment with gemcitabine maintained stable disease for 4 mo., Conclusion: The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Surgical treatment is the gold standard for the treatment of early-stage non-small-cell lung cancer. However, minimally invasive tumour ablation can be an alternative treatment for patients not eligible for surgery due to comorbidities. The aim of this study was to evaluate the efficacy of photothermal ablation therapy using low-power near-infrared laser and topical injection of indocyanine green (ICG), a photosensitizer, in a preclinical study using a rabbit VX2 lung cancer model., Methods: Six New Zealand white rabbits were used. Five hundred microlitres of a suspension containing 0.5 × 107 VX2 cancer cells with growth factor-reduced Matrigel was inoculated into the right lung using an ultrathin bronchoscope. Three rabbits were treated with laser ablation therapy with topical injection of ICG, whereas another 3 rabbits were treated with laser ablation alone. All tumours were irradiated with a laser with 500-mW output at 808 nm for 15 min. The tumours were examined histopathologically to assess the state of ablation., Results: The maximum tumour surface temperatures in rabbits treated using ICG/laser and laser alone were higher than 58°C and lower than 40°C, respectively. The ablated areas in the rabbits treated with ICG/laser were significantly larger than those in the rabbits treated with laser alone (0.49 ± 0.27 vs 0.02 ± 0.002 cm2, respectively) (P < 0.05)., Conclusions: The photothermal treatment using the combination of low-power near-infrared laser and topical injection of ICG can ablate a larger tumour area than laser treatment alone., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Early stage lung cancers which localized in the middle layer or the center of the lung become indications for anatomical segmentectomy. As a method of intraoperative identifying the intra-segmental plane, 2 different techniques utilizing indocyanine green (ICG) fluorescence has been clinically applied. The one is a method of systemically intravenous administration of ICG after ligating the objective segmental pulmonary artery. The other is a method of insufflate the diluted ICG into the objective segmental bronchus under the bronchoscope. The segmental alveoli were visualized with a ICG fluorescence thoracoscope. Both methods visualize inter-segmental plane. Both advantages and disadvantages were discussed. These methods may help the repertoire of atypical segmentectomy getting wider. Also, ICG fluorescence imaging is incorporated into a robotic surgery. ICG fluorescence imaging is expected to be applied to various applications of thoracic surgery.

The increasing need for pulmonary resection by video-assisted thoracoscopic surgery (VATS) has presented a greater opportunity to detect small-sized pulmonary nodules by computed tomography (CT). In cases where it is difficult to identify tumor localization intraoperatively, it is necessary to place the VATS marker near the pulmonary nodules before surgery. Conventional percutaneous or bronchoscopic VATS marker placement under local anesthesia is accompanied by patient pain. We clinically applied a new technique to place VATS markers using a bronchoscope under general anesthesia in a hybrid operating room. Multiple pulmonary nodules were successfully marked and securely excised simultaneously by VATS. This technique enables secure, minimally invasive resection of multiple small-sized pulmonary nodules without causing distress to the patient., (© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: A novel liposomal nanoparticle, CF800, that co-encapsulates indocyanine green for near-infrared (NIR) imaging and iohexol for computed tomography (CT) imaging has shown preferential tumor accumulation after intravenous injection by the enhanced permeability and retention effect. We hypothesized that CF800-enhanced NIR imaging would facilitate intraoperative localization of small lung nodules., Methods: A rabbit VX2 lung tumor model was implemented. CF800 was injected intravenously, followed by sequential CT acquisitions to track the biodistribution of CF800. Eleven rabbits were used for NIR fluorescence evaluation after thoracotomy at time points until 7 days after injection by using a NIR fluorescence thoracoscope in vivo. Organs of interests were removed for ex vivo analysis by using NIR imaging. Tumor-to-background (inflated lung) ratio was calculated and compared among the time points., Results: Both CT and NIR imaging indicated enhanced accumulation of CF800 within the VX2 tumor. NIR image analysis revealed the highest tumor-to-background ratio on days 4 and 5. High background at day 2 and low tumor signal at day 7 prevented distinct demarcation. Metastatic pulmonary small nodules (less than 2 mm in diameter) were successfully visualized by NIR imaging on day 4. However, NIR signal penetration was limited, resulting in localization failure for the few tumors deep (>0 mm) to the lung surface., Conclusions: NIR image-guided localization of small lung nodules appears to be feasible under certain conditions. However, further refinement will be required to increase tumor signal intensity and to reduce background signal from normal lung parenchyma, which is at least in part a consequence of persistent CF800 in the vasculature., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: During anatomical lung resection in high-risk patients, the bronchial stump is covered with tissue flaps (e.g. pericardial fat tissue and intercostal muscle) to prevent bronchopleural fistula development. This is vital for reliable reinforcement of the bronchial stump. We evaluated the blood supply of the flap using indocyanine green fluorescence (ICG-FL) and thermography intraoperatively in 27 patients at high risk for developing a bronchopleural fistula., Methods: Before reinforcing the stump with a flap, the fluorescence agent was intravenously injected and the blood supply was evaluated. The surface temperature of the flap was measured with thermography. The two modalities were then compared., Results: ICG-FL intensity and surface temperature on the distal compared to the proximal side of the flap decreased by 32.6 ± 29.4% (P < 0.0001) and 3.5 ± 2.0°C (P < 0.0001), respectively. In patients with a higher ICG-FL intensity value at the tip than the median, the surface temperature at the tip decreased by 2.7 ± 1.7°C compared to the proximal side. In patients with a lower ICG-FL value at the tip, the surface temperature decreased by 4.6 ± 1.7°C (P = 0.0574). The bronchial stump reinforced the part of the flap with adequate blood supply; none of the patients developed a bronchopleural fistula., Conclusions: ICG-FL confirmed variation in the blood supply of the intercostal muscle flap, even if prepared using the same surgical procedure. Thermography analysis tends to correlate with the fluorescence method, but may be influenced by the state of flap preservation during surgery., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The AminoIndex TM Cancer Screening (AICS) system, a plasma-free amino acid (PFAA)-based multivariate discrimination index, is a blood screening test for lung cancer based on the comparison of PFAA concentrations between patients with lung cancer and healthy controls. Pre- and post-operative AICS values were compared among 72 patients who underwent curative resection for lung cancer. Post-operative changes in PFAA concentrations were also evaluated. AICS values were classified as rank A (0.0-4.9), B (5.0-7.9), or C (8.0-10.0). Rank B-C patients were evaluated for outcomes and post-operative changes in their AICS values. Twenty-three of the 44 pre-operative rank B-C patients experienced post-operative reductions in AICS rank. Only one patient experienced cancer recurrence. Post-operative changes in PFAA concentrations were associated with the risk of post-operative cancer recurrence (p = 0.001). Multivariate analysis revealed that the absence of a post-operative reduction in AICS rank independently predicted cancer recurrence (hazard ratio: 14.28; p = 0.012). The majority of patients had high pre-operative AICS values and exhibited a reduction in AICS rank after curative resection. However, the absence of a post-operative reduction in AICS rank was associated with cancer recurrence, suggesting that AICS rank may be a sensitive marker of post-operative recurrence.

Background: Minimally invasive video-assisted thoracoscopic surgery for small-sized pulmonary nodules is challenging, and image-guided preoperative localisation is required. Near-infrared indocyanine green fluorescence is capable of deep tissue penetration and can be distinguished regardless of the background colour of the lung; thus, indocyanine green has great potential for use as a near-infrared fluorescent marker in video-assisted thoracoscopic surgery., Methods: Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to undergo video-assisted thoracoscopic wedge resection, were enrolled in this study. A mixture of diluted indocyanine green and iopamidol was injected into the lung parenchyma as a marker, using either computed tomography-guided percutaneous or bronchoscopic injection techniques. Indications and limitations of the percutaneous and bronchoscopic injection techniques for marking nodules with indocyanine green fluorescence were examined and compared., Results: In the computed tomography-guided percutaneous injection group (n = 15), indocyanine green fluorescence was detected in 15/15 (100%) patients by near-infrared thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and subsequent marking was unsuccessful after a pneumothorax occurred. In the bronchoscopic injection group (n = 22), indocyanine green fluorescence was detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected., Conclusion: Either computed tomography-guided percutaneous or bronchoscopic injection techniques can be used to mark pulmonary nodules with indocyanine green fluorescence. Indocyanine green is a safe and easily detectable fluorescent marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic injection approach enables surgeons to mark multiple lesion areas with less risk of causing a pneumothorax., Trial Registration: UMIN-CTR R000027833 accepted by ICMJE. Registered 5 January 2013.