Eunjue Yi

Anticancer efficacy of photodynamic therapy with hematoporphyrin-modified, doxorubicin-loaded nanoparticles in liver cancer.

Photodynamic therapy (PDT) in combination with chemotherapy has great potential for cancer treatment. However, there have been very few attempts to developing cancer-targeted co-delivered systems of photosensitizers and anticancer drugs. We developed hematoporphyrin (HP)-modified doxorubicin (DOX)-loaded nanoparticles (HP-NPs) to improve the therapeutic effect of PDT in treating liver cancer. HP is not only a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells but also a well-known photosensitizer for PDT. In vitro phototoxicity in HepG2 (human hepatocellular carcinoma) cells and in vivo anticancer efficacy in HepG2 tumor-bearing mice of free HP and HP-NPs were evaluated. The in vitro phototoxicity in HepG2 cells determined by MTT assay, annexin V-FITC staining and FACS analysis was enhanced in HP-NPs compared with free HP. Furthermore, compared with free HP-based PDT, in vivo anticancer efficacy in HepG2 tumor-bearing mice was markedly improved by HP-NPs-based PDT. Moreover, in both cases, the therapeutic effect was increased according to the irradiation time and number of PDT sessions. In conclusion, the HP-NPs prepared in this study represent a potentially effective co-delivery system of photosensitizer (HP) and anticancer drug (DOX) which improved the effects of PDT in liver cancer.

Hypocrellin B and paclitaxel-encapsulated hyaluronic acid-ceramide nanoparticles for targeted photodynamic therapy in lung cancer.

To increase the therapeutic efficacy of photodynamic therapy (PDT) in treating lung cancer, we developed both photosensitizer and anticancer drug encapsulated hyaluronic acid-ceramide nanoparticles. Based on our previous study, a co-delivery system of photosensitizers and anticancer agents greatly improves the therapeutic effect of PDT. Furthermore, hyaluronic acid-ceramide-based nanoparticles are ideal targeting carriers for lung cancer. In vitro phototoxicity in A549 (human lung adenocarcinoma) cells and in vivo antitumor efficacy in A549 tumor-bearing mice treated with hypocrellin B (HB)-loaded nanoparticles (HB-NPs) or hypocrellin B and paclitaxel loaded nanoparticles (HB-P-NPs) were evaluated. Cell viability assay, microscopic analysis and FACS analysis were performed for the in vitro studies and HB-P-NPs showed enhanced phototoxicity compared with HB-NPs. In the animal study, the tumor volume change and the histological analysis was studied and the anticancer efficacy improved in the order of free HB<HB-NPs<HB-P-NPs. In conclusion, the combination therapy of PDT and chemotherapy, and hyaluronic acid-ceramide nanoparticle-based targeted delivery improved the effects of PDT in lung cancer in mice.

Clinical outcome of photodynamic therapy in esophageal squamous cell carcinoma

The aim of this study was to evaluate the feasibility and safety of photodynamic therapy (PDT) as a curative treatment option or as palliative therapy for esophageal squamous cell carcinoma. Medical records of patients who received PDT for esophageal squamous cell carcinoma, including carcinoma in situ, were reviewed retrospectively. Survival analysis was performed using the Kaplan-Meier method. A total of 31 cases were treated with PDT between 2003 and 2013. Treatment was for palliative purposes in 11 cases (35.5%) and for therapeutic purposes in 20 cases (64.5%). We achieved 15 cases (48.4%) of complete remission and 16 (51.6%) cases of partial remission during the follow-up period. There were 6 fatalities, 5 of which were related to disease progression. Complications, including benign strictures, occurred in 11 cases (35.5%) but there was only 1 complication-related death. Recurrence occurred in 2 patients with complete remission. Overall survival was 31.9 months for patients with complete remission and 28.2 months for those with partial remission. Disease-free survival of patients with complete remission was 21.9 months. Our data suggest that photodynamic therapy is a reasonable palliative treatment option with acceptable complication rates for esophageal cancer and could be performed for therapeutic purposes in cases of early esophageal cancer.

Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination

BACKGROUND This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. METHODS Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. RESULTS A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. CONCLUSIONS IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC.

Clinical results of photodynamic therapy in tracheobronchial malignancy.

Photodynamic therapy (PDT) has been adopted as an alternative therapy for lung cancer patients who could not receive surgery due to their poor condition. It also has expanded its roles in lung cancer treatment for palliative treatment for increasing symptoms. We retrospectively reviewed medical records of patients of tracheobronchial cancers who received photodynamic therapy in our institute. Outcomes of the treatment results were evaluated, and survival analysis was performed via Kaplan-Meier analysis. We performed 25 cases of photodynamic therapy for tracheobronchial cancer patients between 2003 and 2013. A total of 21 patients were involved. Average ages at the time of treatment were 68.1. In those 25 cases, 8 cases achieved complete remission, and 15 cases remained partial remission. There were 2 cases of no response. Seven patients died during the follow-up periods, but none of these were related with complications. Only two minor complications were observed during the follow-up periods. One was granulation at the site of PDT, and the other was hemoptysis. Average overall survival periods for the therapeutic group were 50.1 months and those of the palliative group were 29.3 months. Photodynamic therapy was safe and feasible for palliative therapy in tracheobronchial cancer with acceptable complication rates. Also, it could be a treatment option for double primary lung cancer in inoperable patients.

Analysis of postoperative outcomes for surgically resected esophageal squamous cell carcinoma reconstructed with gastric conduit

Background: To investigate the postoperative outcomes and complication management results after esophagectomy with gastric conduit reconstruction for esophageal squamous cell carcinomas. Methods: The medical records of patients with esophageal squamous cell carcinoma who underwent esophagectomy and gastric conduit reconstruction in a single institute by a single surgeon (Dr. Jheon) between 2003 and 2013 were retrospectively reviewed. Patients who underwent transhiatal esophagectomy or simultaneous hypopharyngeal cancer operation were excluded. Postoperative outcomes including complication management were investigated, and survival analysis was performed. Results: A total of 105 patients were enrolled in this study. Mean follow-up period was 47.5±33.98 (range, 1.7 to 126.7) months, mean age was 64.0±8.81 (range, 24 to 84) years, and mean hospital stay was 15.2±12.6 (range, 9 to 96) days. Perioperative complication rate was 24.8%, and the incidence of esophageal stenosis was 13.3%. The most commonly observed perioperative complication was vocal cord palsy, which occurred in 14 patients (13.3%). Pneumonia occurred in 4 patients (3.8%), and one developed into acute respiratory distress syndrome (ARDS). Wound problems were observed in 8 patients (7.6%), and half of them (4 patients) required surgical intervention. Incidence of anastomotic leak was 2.9% (3 patients), and only one patient required surgical intervention. Overall 3- and 5-year survival rates were 65.2% and 57.9%, respectively. Overall 3- and 5-year recurrence-free survival rates were 64.0% and 55.6%, respectively. A total of 42 patients died during the follow-up period; however, no postoperative mortality (within 30 days after surgery) was observed. Complication-related death was observed in 2 cases (fistula bleeding and aspiration pneumonia). Twenty-four patients died of cancer progression, 6 patients died of pneumonia, and the other deaths were not related to cancer or complications. Anastomotic leak was related with significantly lower overall and recurrence-free survival (P Conclusions: Esophagectomy combined with gastric conduit reconstruction is a safe and established surgical treatment for esophageal squamous cell carcinoma. Appropriately controlled postoperative complications may not affect postoperative outcomes. However, considerable complications such as anastomotic leak or recurrent laryngeal nerve palsy could influence long term survival.

Community for thoracoscopic surgery

Video-assisted thoracoscopic surgery (VATS) is a real game changer in thoracic surgery. Surgical environment for thoracic surgeon have become complicated more and more as the techniques and technology have been advanced. No single surgeon can stand alone in this rapid changing circumstance. Surgeons need to meet, talk together, and discuss what they have done. There may be no perfect answers, however, surgeon will get to know which way is better. Although the chosen one could be different from each of them, surgeons can debates and conclude the consensus. Societies for thoracic surgeons could provide the platforms for discussion, arguing, sharing experiences, educations, and therefore achievement another innovations comparable to VATS.

Association of MAGE A1-6 Expression with Lung Cancer Progression

The melanoma-associated antigen (MAGE) genes are known to be expressed in various kinds of tumors including lung cancer. Although they are studied as targets for immunotherapy and tools for early detection of lung cancer, the correlation between MAGE expression and the prognosis in lung cancer has not been clarified. In this study, we evaluated the relationship between MAGE A1-6 gene expression and the clinical prognosis in lung cancer. Bone marrow aspirations were performed in 60 patients who were diagnosed as lung cancer and underwent lung cancer surgery between 2007 and 2008. Each bone marrow was examined using nested reverse transcription- polymerase chain reaction (RT-PCR) with the MAGE common primer to detect MAGE A1-6. Overall survival rate, disease-free survival rate, recurrence, and distant metastasis were reviewed retrospectively. Survival periods were analyzed using SPSS ver. 20.0. Of the total 60 lung cancer patients, 9 patients (15%) had MAGE A1-6. MAGE A1-6-positive patients showed poor overall survival and overall disease-free survival rates (43.8 ± 26.1, 43.2 ± 26.9 months, respectively) compared with MAGE A1-6-negative patients (54.4 ± 17.2, 44.8 ± 22.1 months, respectively). No significant difference was shown in either survival rates. In conclusion, MAGE A1-6 expression of bone marrow in lung cancer patients correlated with poor survival rates. We suggest that MAGE A1-6 may be considered as a novel prognostic factor for lung cancer which leads to effective follow-up and treatment.

Perioperative outcomes of upper lobectomy according to preservation or division of the inferior pulmonary ligament.

BACKGROUND The aim of this study was to investigate the relationship between inferior pulmonary ligament division and postoperative complications. METHODS Medical records of 72 non-small cell lung cancer (NSCLC) patients who underwent video-assisted thoracic surgery (VATS) upper lobectomy between March 2012 and November 2013 performed by a single thoracic surgeon at our center were reviewed retrospectively. Patients were categorized into two groups: the division group, who underwent division of the inferior pulmonary ligament, and the preservation group, who did not. The division group included 43 patients (27 right, 16 left), while the preservation group included 29 (11 right, 18 left). Postoperative outcomes such as the presence of pleural effusion, chest tube duration, and changes in the angle and diameter of remnant bronchus were compared; bronchial diameter and angle were measured on three-dimensional (3D) reconstruction chest CT images. RESULTS Chest tube duration, duration of chest tube drainage >200 mL, and the presence of pleural effusion on chest X-rays taken 1 month after surgery were not significantly different between the two groups (P=0.07, 0.33, and 1.00, respectively). There were also no significant differences between groups in the presence of apical dead space or in change in bronchial angle (P=0.22 and 0.74, respectively). In 3D reconstruction images, changes in the diameter of the right middle, right lower, and left lower lobar (LLL) bronchi were similar between groups (P=0.72, 0.12 and 0.29, respectively). Change in the angle between the right bronchus intermedius (RBI) and the right middle lobar (RML) bronchus and between the RBI and the right lower lobar (RLL) bronchus were significantly different between the division and preservation groups (P=0.02 and 0.05, respectively). CONCLUSIONS Inferior pulmonary ligament division had no clear benefits. Complications related to excessive dislocation of remnant bronchi might be associated with inferior pulmonary ligament division, but further research is needed to elucidate this relationship.

Evaluate the outcome of pneumonectomy for stage III a-N2 NSCLC

Results During the study, 184 patients underwent surgical resection of stage III a-N2 non-small cell lung cancer. Among them, 35 patients had pneumonectomy, 29 patients (83%) were male, and 6 (17%) were female. The median age was 57 years (43 yrs-77 yrs) old, and the median follow up duration was 77 month. 27 patients (77%) had induction chemotherapy before operation. Right pneumonectomy was performed in 13 patients (37%), and Left pneumonectomy was done in 22 patients (63%). The 5-year survival was 58% in pneumonectomy, 28% in the right pneumonectomy and 76% in the left pneumonectomy, respectively. Left pneumonectomy(p = 0.021) and complete resectability (p = 0.017) were positive prognostic factor, but the induction chemotherapy before operation was negative prognostic factor. (p = 0.040)