• Korean Journal of Radiology
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• v.23 no.1
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• pp.112-123
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• 2022

Objective: To investigate the relationship between ¹⁸F-FDG PET/CT semi-quantitative parameters and the International Association for the Study of Lung Cancer, American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) histopathologic classification, including histological subtypes, proliferation activity, and somatic mutations. Materials and Methods: This retrospective study included 419 patients (150 males, 269 females; median age, 59.0 years; age range, 23.0-84.0 years) who had undergone surgical removal of stage IA-IIIA lung adenocarcinoma and had preoperative PET/CT data of lung tumors. The maximum standardized uptake values (SUVmax), background-subtracted volume (BSV), and background-subtracted lesion activity (BSL) derived from PET/CT were measured. The IASLC/ATS/ERS subtypes, Ki67 score, and epidermal growth factor/anaplastic lymphoma kinase (EGFR/ALK) mutation status were evaluated. The PET/CT semi-quantitative parameters were compared between the tumor subtypes using the Mann-Whitney U test or the Kruskal-Wallis test. The optimum cutoff values of the PET/CT semi-quantitative parameters for distinguishing the IASLC/ATS/ERS subtypes were calculated using receiver operating characteristic curve analysis. The correlation between the PET/CT semi-quantitative parameters and pathological parameters was analyzed using Spearman's correlation. Statistical significance was set at p < 0.05. Results: SUVmax, BSV, and BSL values were significantly higher in invasive adenocarcinoma (IA) than in minimally IA (MIA), and the values were higher in MIA than in adenocarcinoma in situ (AIS) (all p < 0.05). Remarkably, an SUVmax of 0.90 and a BSL of 3.62 were shown to be the optimal cutoff values for differentiating MIA from AIS, manifesting as pure ground-glass nodules with 100% sensitivity and specificity. Metabolic-volumetric parameters (BSV and BSL) were better potential independent factors than metabolic parameters (SUVmax) in differentiating growth patterns. SUVmax and BSL, rather than BSV, were strongly or moderately correlated with Ki67 in most subtypes, except for the micropapillary and solid predominant groups. PET/CT parameters were not correlated with EGFR/ALK mutation status. Conclusion: As noninvasive surrogates, preoperative PET/CT semi-quantitative parameters could imply IASLC/ATS/ERS subtypes and Ki67 index and thus may contribute to improved management of precise surgery and postoperative adjuvant therapy.

• Herbal Formula Science
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• v.31 no.4
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• pp.361-371
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• 2023

Objectives : Gastric cancer is a malignant tumor of the digestive tract that not only has a high mortality rate, but also affects quality of life. In Traditional Korean Medicine, acupuncture and herbal medicines can increase the survival rate for Gastric cancer and improve the quality of life. Traditional Korean Medicine treatment played an important role when used alone or in combination with chemotherapy. However, there is still insufficient evidence to support the efficacy and safety of Traditional Korean Medicine in patients undergoing chemotherapy after surgery. Therefore, the purpose of this study is to systematically evaluate the effect of oriental medicine treatment on patients as a complementary therapy for Gastric cancer. Methods : 2 researchers will search using EMBASE, Pubmed, CNKI, Cochrane Library, CiNii, KMBASE, KISS, OASIS, RISS, ScienceON. The search period of the database is from inception until June 2022. This study will include a randomized controlled trial of GC for acupuncture and herbal treatment. Primary outcomes include anti-cancer effects. Secondary outcomes evaluate survival rates and improvements in quality of life. The data uses Review Manager Software 5.4. Results : This study will provide a systematic evaluation by synthesizing the anti-cancer effect, survival rate and quality of life of Gastric cancer when Traditional Korean Medicine is combined with chemotherapy. Conclusion : The conclusion of this study will provide a basis for determining whether Traditional Korean Medicine treatment for Gastric cancer treatment is an effective and safe treatment method in clinical practice.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.368-378
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• 2024

Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44^highCD133^high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

• Journal of Gastric Cancer
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• v.24 no.3
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• pp.267-279
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• 2024

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. Materials and Methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients. All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients. Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Conclusions: Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

• Radiation Oncology Journal
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• v.25 no.1
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• pp.34-42
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• 2007

[ $\underline{Purpose}$ ]: We performed a retrospective non-randomized clinical study of locally advanced rectal cancer, to evaluate the anal sphincter preservation rates, down staging rates and survival rates of preoperative chemoradiotherapy. $\underline{Materials\;and\;Methods}$: From January 2002 to December 2005, patients with pathologically confirmed rectal cancer with clinical stage T2 or higher, or patients with lymph node metastasis were enrolled in this study. A preoperative staging work-up was conducted in 36 patients. All patients were treated with preoperative chemoradiotherapy, and curative resection was performed for 26 patients at Hallym University Sacred Heart Hospital. Radiotherapy treatment planning was conducted with the use of planning CT for all patients. A total dose of $45.0{\sim}52.2\;Gy$ conventionally fractionated three-dimensional radiotherapy was delivered to the whole pelvis. Chemotherapy was given at the first and fifth week of radiation therapy with continuous infusion i.v. 5-FU (Fluorouracil) and LV (Leucovorine). Surgical resection was performed 2 to 4 weeks after the completion of the chemoradiotherapy regimen. $\underline{Results}$: The complete resection rate with negative resection margin was 100% (26/26). However, a pathologically complete response was not seen after curative resection. Surgery was done by LAR (low anterior resection) in 23 patients and APR (abdomino-perineal resection) in 3 patients. The sphincter preservation rate was 88.5% (23/26), down staging of the tumor occurred in 12 patients (46.2%) and down-sizing of the tumor occurred in 19 patients (73%). Local recurrence after surgical resection developed in 1 patient, and distant metastasis developed in 3 patients. The local recurrence free survival rate, distant metastasis free survival rate, and progression free survival rate were 96.7%, 87% and 83.1%, respectively. Treatment related toxicity was minimal except for one grade 3, one grade 4 anemia, one grade 3 leukopenia, and one grade 3 ileus. $\underline{Conclusion}$: Preoperative concurrent chmoradiotherapy for locally advanced rectal cancer seems to have some potential benefits: high sphincter preservation and down staging. Treatment related toxicity was minimal and a high compliance with treatment was seen in this study. Further long-term follow-up with a larger group of patients is required.

• The Journal of the Korean bone and joint tumor society
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• v.14 no.2
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• pp.163-171
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• 2008

Purpose: We analyze the characteristics of soft tissue sarcomas presented with hematoma, which were misdiagnosed as simple hematoma initially and the proper management were delayed. Materials and Methods: The 7 patients with histologically proven soft tissue sarcoma with hematoma presented since February 1997 were evaluated retrospectively. Neither patient had a medical history of bleeding tendency nor anticoagulant therapy. Two of them had minor traumas. There were 2 men and 5 women. Average follow up period was 58 months. MRI findings, provided treatments and oncologic outcome were reviewed with the reference of related articles. Results: Retrospective review of initial MR images revealed deep seated intramuscular masses with focal solid enhanced nodules at the peripheral margin. The diagnoses were delayed at least 1 month in 3 of them which included 2 cases of simple hematoma evacuation without biopsy initially. After histologic diagnosis of soft tissue sarcoma, wide resections were performed in 4 cases. one patient underwent above knee amputation and the remained 2 patients were managed with wide resection followed by amputation due to local recurrence. At last follow up there were CDF and NED in 2 cases, respectively and AWD in 3 cases. Conclusion: To avoid the delay of diagnosis and treatment of soft tissue sarcomas presented with hematoma, high degree of clinical suspicion, careful analysis of MR images and early biopsy were important.

• Radiation Oncology Journal
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• v.17 no.1
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• pp.43-51
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• 1999

Purpose : To discuss the technical aspect of interstitial brachytherapy including method of implant, insertion time of radioactive source, total radiation dose, and complication, we reviewed patients who had diagnoses of soft tissue sarcoma and were treated by conservative surgery, interstitial implant and external beam radiation therapy Materials and Methods : Between May 1995 and Dec. 1997, ten patients with primary or recurrent soft tissue sarcoma underwent surgical resection (wide margin excision) and received radiotherapy including interstitial brachytherapy. Catheters were placed with regular intervals of 1 ~l.5 cm immediately after tumor removal and covering the critical structures, such as neurovascular bundle or bone, with gelform, muscle, or tissue expander in the cases where the tumors were close to those structures. Brachytherapy consisted of high dose rate, iridium-192 implant which delivered 12~15 Gy to 1 cm distance from the center of source axis with 2~2.5 Gy/fraction, twice a day, starting on 6th day after the surgery, Within one month after the surgery, total dose of 50~55 Gy was delivered to the tumor bed with wide margin by the external beam radiotherapy. Results : All patients completed planned interstitial brachytherapy without acute side effects directly related with catheter implantation such as infection or bleeding. With median follow up duration of 25 months (range 12~41 months), no local recurrences were observed. And there was no severe form of chronic complication (RTOGIEORTC grade 3 or 4). Conclusion : The high dose rate interstitial brachytherapy is easy and safe way to minimize the radiation dose delivered to the adjacent normal tissue and to decrease radiation induced chronic morbidity such as fibrosis by reducing the total dose of external radiotherapy in the management of soft tissue sarcoma with conservative surgery.

• Radiation Oncology Journal
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• v.26 no.3
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• pp.160-165
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• 2008

Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.536-542
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• 1999

Background: The purpose of this study is to improve the quality of the diagnostic procedures in the preoperative evaluation so as to reduce the unnecessary thoracotomy and to ensure resectability in non-small cell lung cancer. Material and Method: Of 616 patients who underwent thoracotomy for primary lung cancer from January 1990 to December 1996, 59 patients(9.6%) turned out to have inoperable lesions after the thoracotomy. We reprospectively reviewed the bronchoscopic findings, methods of tissue diagnosis, CT scans, pulmonary function test and lung perfusion scan, reasons for nonresectability, and adjuvant therapy, and then followed up on the survival rate after exploratory thoracotomy. Result: The cell types were squamous cell carcinoma in 38, adenocarcinoma in 15, large cell carcinoma in 3 and others in 3. Primary loci were RUL in 20, RML in 6, RLL in 8, LUL in 13, LLL in 4 and others in 8. The reasons for non-resectability were various; direct tumor invaison to mediastinal structures(n=41), seeding on pleural cavity(n=8), poor pulmonary function(n=2), invasions to extranodal mediastinal lymph node(n=2), technical non- resectability due to extensive chest wall invasion (n=3), small cell carcinoma (n=1), malignant lymphoma(n=1), and multiple rib metastases(n=1). In the follow-up of 58 patients, 1-year survival rate was 55.2% and 2-year survival rate was 17.2% and the mean survival time was 14 months. When compared according to cell types or postoperative adjuvant therapeutic modalities, no significant difference in the survival rates were found. The squamous cell carcinoma was frequently accompanied by local extension to contiguous structures and was the main cause of non-resectability. In adenocarcinoma, pleural seeding with malignant effusion was frequently encountered, and was the major reason for non-resectability. Conclusion: These data revealed that if appropriate preoperative diagnostic tools had been available, many unnecessary thoracotomies could have been avoided. Both the use of thoracoscopy in selected cases of adenocarcinoma and the more aggressive surgical approach to the locally advanced tumor could reduce the incidence of unnecessary thoracotomies for non-small cell lung cancers.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.314-320
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• 2006

Background : The overall response (20-30%) to chemotherapy in non-small cell lung cancer (NSCLC) is quite poor. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in heme degradation. There is increasing evidence suggesting that the induction of HO-1 might have an important protective effect against oxidative stress including cisplatin containing chemotherapy. This study retrospectively investigated the relationship between HO-1 expression and the response to chemotherapy containing cisplatinin advanced NSCLC patients. Material and Methods : The medical records including the responses to chemotherapy of fifty nine cases were evaluated retrospectively, and the tissue samples of these patients were immunohistochemically stained for HO-1. Results : Forty three of the fifty nine patients(72.8%) showed positive staining for HO-1 in their cancer tissues. There was no significant difference according to the cell type, stage and tumor size. In addition, there was no correlation between HO-1 expression and the responses to chemotherapy. Conclusion : HO-1 expression in tumor tissue dose not predict the response to cisplatin containing chemotherapy in advanced NSCLC. Further prospective studies with a larger number of patients will be needed to confirm these results.