• Journal of Korean Neurosurgical Society
• /
• v.64 no.6
• /
• pp.983-994
• /
• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

• Investigative Magnetic Resonance Imaging
• /
• v.9 no.2
• /
• pp.109-116
• /
• 2005

Purpose : To determine the usefulness of additional Mn-DPDP MRI for preoperative evaluation of the patients with colorectal cancers by comparison of dual-phase CT scan, Mn-DPDP enhanced MRI and combination of CT and MRI. Materials and Methods : Fifty-three colorectal cancer patients with 92 metastatic nodules underwent dualphase (arterial and portal) helical CT scan and Mn-DPDP MRI prior to surgery. The indication of MRI was presence or suspected of having metastatic lesions at CT scan and/or increased serum carcinoembryonic antigen (CEA) levels (10 ng/mL or more). The diagnosis was established by the combination of findings at surgery, intraoperative ultrasonography, and histopathologic examination. Two radiologists interpreted CT, MRI, and combination of CT-MRI at discrete sessions and evaluated each lesion for location, size, and intrinsic characteristics. The lesions were divided into three groups according to their diameter; 1cm<, 1-2 cm, and >2 cm. Diagnostic accuracy was evaluated using the alternative-free response receiver operating characteristic method. Detection and false positive rate were also evaluated. Results : In the lesions smaller than 1 cm, detection rate of combined CT-MRI was superior to CT or MRI alone (82%, p=0.036). The mean accuracy (Az values) of combined CT and MRI was significantly higher than that of CT in the lesions smaller than 2 cm (1 cm<, p=0.034; 1-2 cm, p=0.045). However, there was no significant difference between MRI and combined CT-MRI. The false positive rate of CT was higher than those of combined CT-MR in the lesions smaller than 1 cm (28%, p=0.023). Conclusion : Additional MRI using Mn-DPDP besides routine CT scan was helpful in differentiating the hepatic lesions (<2 cm) and could improve detection of the small hepatic metastases (<1 cm) from colorectal carcinoma.

• Nuclear Medicine and Molecular Imaging
• /
• v.40 no.6
• /
• pp.309-315
• /
• 2006

Purpose: Accurate evaluation of cervical lymph node (LN) metastasis of head and neck squamous cell canter (SCC) is important to treatment planning. We evaluated the diagnostic accuracy of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the detection of cervical LN metastasis of head and neck SCC and performed a retrospective comparison with CT/MRI findings. Materials & Methods: Seventeen patients with pathologically proven head and neck SCC underwent F-18 FDG PET/CT and CT/MRI within 4 week before surgery. We recorded lymph node metastases according to the neck level system of imaging-based nodal classification. F-18 FDG PET/CT images were analyzed visually for assessment of regional tracer uptake in LN. We analyzed the differences in sensitivity and specificity between F-18 FDG PET/CT and CT/MRI using the Chi-square test. Results: Among the 17 patients, a total of 123 LN levels were dissected, 29 of which showed metastatic involvement. The sensitivity and specificity of F-18 FDG PET/CT for detecting cervical LN metastasis on a level-by-level basis were 69% (20/29) and 99% (93/94). The sensitivity and specificity of CT/MRI were 62% (18/29) and 96% (90/94). There was no significant difference in diagnostic accuracy between F-18 FDG PET/CT and CT/MRI. Interestingly, F-18 FDG PET/CT detected double primary tumor (hepatocellular carcinoma) and rib metastasis, respectively. Conclusion: There was not statistically significant difference of diagnostic accuracy between F-18 FDG PET/CT and CT/MRI for the detection of cervical LN metastasis of head and neck SCC. The low sensitivity of F-18 FDG PET/CT was due to limited resolution for small metastatic deposits.

• The Korean Journal of Nuclear Medicine
• /
• v.33 no.1
• /
• pp.76-83
• /
• 1999

Purpose: We performed this study to compare T1-201 and Tc-99m MIBI scans for the differentiation of malignant from benign breast mass. Materials and Methods: Thirty-eight female patients underwent T1-201 breast scan and thirty-two of them also underwent Tc-99m MIBI scan of the breast. After intravenous injection of 74-111 MBq of T1-201, early (10 minutes) and delayed (3 hours) images were obtained. Then, 555-740 MBq of Tc-99m MIBI was injected and images after 30 minutes were obtained. We compared T1-201 and Tc-99m MIBI scans with pathologic results. Results: Twenty-three patients were confirmed to have infiltrating duct carcinoma and fifteen patients to have benign breast mass by excisonal biopsy. The sensitivity of early and delayed T1-201 scan and Tc-99m MIBI scan in the detection of malignant breast lesion were 100% (23/23), 82% (18/22), and 90% (18120), respectively. The sensitivity of early T1-201 scan was significantly higher than that of delayed T1-201 scan (p<0.05). The specificity of early and delayed T1-201 scan and Tc-99m MIBI scan were 73% (l1/15), 73% (l1/15) and 83% (10/12), respectively (p: not significant). Three patients out of nine with fibroadenoma and one patient with atypical duct hyperplasia were false positive in both early and delayed T1-201 scans. The size of fibroadenoma with false positive in early and delayed T1-201 scan (4 cases) was larger than that of 11 fibroadenoma with true negative scan (p<0.01). Metastatic axillary lymph node involvement was present in fifteen patients. The sensitivity to detect metastatic nodes was 38% (5/13) for early T1-201 images, 15% (2/13) for delayed T1-201 images, 58% (7/12) for Tc-99m MIBI planar images and 67% (4/6) for Tc-99m MIBI SPECT. The sensitivity of Tc-99m MIBI planar or SPECT was significantly higher than that of delayed T1-201 images (p<0.05). Conclusion: Early T1-201 and Tc-99m MIBI scan are useful noninvasive methods to differentiate malignant from benign mass of breast Tc-99m MIBI scan was sensitive in detecting axillary lymph node metastasis in patients with breast cancer.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.38 no.11
• /
• pp.1535-1542
• /
• 2009

To find the new use of Korean ginseng and mushroom, crude polysaccharides were prepared from submerged cultures of Hericium erinaceum in the medium supplemented with Korean ginseng extracts. When we fractionated crude polysaccharides (HE-GE-CP-1, 3, and 5) from hot-water extracts of submerged cultures of H. erinaceum with ginseng extracts (1%, 3%, and 5% addition of total medium), the yields of HE-GE-CP-1, 3, and 5 were identified at 5.7, 5.1, and 4.8%, respectively. Among crude polysaccharide fractions, HE-GE-CP-5 was significantly higher (1.89-fold of the saline control) than those of HE-GE-CP-1 (1.64-fold) or HE-GE-CP-3 (1.76-fold) on mitogenic activity of splenocytes. HE-GE-CP-5 also had the more potent bone marrow cell proliferation (1.83-fold) rather than HE-CP or HE-GE-CP-1 or HE-GE-CP-3 (1.59- or 1.44- or 1.69-fold, respectively), and anti-metastatic activity as anti-cancer effect showed the highest prophylactic value (72.4% inhibition of tumor control) in 5% supplementation of ginseng extract. However, the lysosomal phosphatase of macrophage was significantly stimulated after HE-GE-CP-3 treatment (2.03-fold). In addition, the immunostimulating and anti-metastatic crude polysaccharide, HE-GE-CP-5, contained mainly neutral sugars (63.2%) with considerable amounts of uronic acid (19.3%) and a small amount of proteins (8.8%). HE-GE-CP-5 can stimulate immune system to inhibit tumor metastasis, and its anti-tumor metastasis may be associated with macrophages, splenocytes and Peyer's patch cells activation.

• Radiation Oncology Journal
• /
• v.25 no.1
• /
• pp.16-25
• /
• 2007

[ $\underline{Purpose}$ ]: Breast conserving surgery (BCS) followed by chemotherapy (CTx.) and radiation therapy (RT) is widely performed for the treatment of early breast cancer. This retrospective study was undertaken to evaluate our interim results in terms of failure patterns, survival and relative risk factors. $\underline{Materials\;and\;Methods}$: From January 1999 through December 2003, 129 patients diagnosed with invasive breast cancer and treated with BCS followed by RT were subject to retrospective review. The median age of the patients was 45 years (age distribution, $27{\sim}76$ years). The proportions of patients according to their tumor, nodes, and metastases (TNM) stage were 65 (50.4%) in stage I, 41 (31.7%) in stage IIa, 13 (10.1%) in stage IIb, 9 (7.0%) in stage III, and 1 patient (0.8%) in stage IIIc. For 32 patients (24.8%), axillary node metastasis was found after dissection. BCS consisted of quadrantectomy in 115 patients (89.1%) and lumpectomy in 14 patients (10.6%). Axillary node dissection at axillary level I and II was performed for 120 patients (93%). For 7 patients (5.4%), only sentinel node dissection was performed with BCS. For 2 patients (1.6%) axillary dissection of any type was not performed. Postoperative RT was given with 6 MV X-rays. A tumor dose of 50.4 Gy was delivered to the entire breast area using a tangential field with a wedge compensator. An aditional dose of $9{\sim}16\;Gy$ was given to the primary tumor bed areas with electron beams. In 30 patients (23.3%), RT was delivered to the supraclavicular node. Most patients had adjuvant CTx. with $4{\sim}6$ cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimens. The median follow-up period was 50 months (range: $17{\sim}93$ months). $\underline{Results}$: The actuarial 5 year survival rate (5Y-OSR) was 96.9%, and the 5 year disease free survival rate (5Y-DFSR) was 93.7%. Local recurrences were noted in 2 patients (true: 2, regional node: 1) as the first sign of recurrence at a mean time of 29.3 months after surgery. Five patients developed distant metastases as the first sign of recurrence at $6{\sim}33$ months (mean 21 months). Sites of distant metastatic sites were bone in 3 patients, liver in 1 patient and systemic lesions in 1 patient. Among the patients with distant metastatic sites, two patients died at 17 and 25 months during the follow-up period. According to stage, the 5Y-OSR was 95.5%, 100%, 84.6%, and 100% for stage I, IIa, IIb, and III respectively. The 5Y-DFSR was 96.8%, 92.7%, 76.9%, and 100% for stage I, IIa, IIb, and III respectively. Stage was the only risk factor for local recurrence based on univariate analysis. Ten stage III patients included in this analysis had a primary tumor size of less than 3 cm and had more than 4 axillary lymph node metastases. The 10 stage III patients received not only breast RT but also received posterior axillary boost RT to the supraclavicular node. During the median 53.3 months follow-up period, no any local or distant failure was found. Complications were asymptomatic radiation pneumonitis in 10 patients, symptomatic pneumonitis in 1 patient and lymphedema in 8 patients. $\underline{Conclusion}$: Although our follow up period is short, we had excellent local control and survival results and reaffirmed that BCS followed by RT and CTx. appears to be an adequate treatment method. These results also provide evidence that distant failure occurs earlier and more frequent as compared with local failure. Further studies and a longer follow-up period are needed to assess the effectiveness of BCS followed by RT for the patients with less than a 3 cm primary tumor and more than 4 axillary node metastases.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.30 no.1
• /
• pp.41-51
• /
• 2008

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.31 no.2
• /
• pp.105-115
• /
• 2005

Purpose: The lymph node status assessed by conventional histological examination is the most important prognostic factor in patients undergoing surgery for oral squamous cell carcinoma. The presence of lymph node metastasis has a strong adverse impact on patient survival even after extended radical resection. Despite these findings, tumour recurrence is not rare after surgery, even when histological examination shows no lymph node metastasis. Recently, molecular-genetically and immunohistochemically demonstrated micrometastasis to the lymph nodes has been shown to have a significant adverse influence on survival in patients with squamous cell carcinoma and histologically negative nodes. The present study sought to determine the incidence and clarify the clinical significance of molecular-genetically and immunohistochemically demonstrated nodal micrometastases and to correlate these data with the stage of oral cancer. Methods: Lymph nodes systematically removed from 71 patients who underwent curative resection between 1998 and 2003 with head and neck squamous cell carcinoma were examined molecular-genetically to detect cytokeratin 5 mRNA with RT-PCR and immunohistochemically to detect cells that stained positively for cytokeratins with the monoclonal antibody cocktail AE1/AE3. The postoperative course and survival rates were compared among patients with and without micrometastases, after numerical classification of overt metastatic nodes. Results: micrometastases were detected in 43(60%) of 71 patients by RT-PCR and 26(36%) of 71 patients by immunohistochemistry. By RT-PCR analysis, patients exhibiting a positive band for CK 5 mRNA had a significantly worse prognosis than those were RT-PCR negative. By immunohistochemistry, the presence of micrometastasis did not predict patient outcome. Conclusion: Micrometastases detected by RT-PCR may be of clinical value in identifying patients who may be at high risk for recurrence and who are therefore likely to benefit from systemic adjuvant therapy.

• The Korean Journal of Food And Nutrition
• /
• v.25 no.4
• /
• pp.941-950
• /
• 2012

In order to develop new physiologically active polysaccharides from persimmon leaves, two different crude polysaccharides were prepared using hot water (PLW-0) and pectinase digestion (PLE-0) and their immuno-stimulating activities were estimated. PLW-0 and PLE-0 showed similar sugar compositions with 15 different sugars, including rarely observed sugars in general polysaccharides such as 2-O-methyl-fucose, 2-O-methyl-xylose, apiose, aceric acid, 3-deoxy-D-manno-2-octulosonic acid, and 3-deoxy-D-lyxo-2-heptulosaric acid, but the uronic acid content of PLE-0 was lower than that of PLW-0 caused by pectinase treatment. Both PLW-0 and PLE-0 showed potent anti-complementary activity in a dose-dependent manner which was similar to a known immuno-stimulating polysaccharide, PSK, from Coriolus versicolor. The activity of PLE-0 at a low concentration ($100{\mu}g/m{\ell}$) was higher than that of PLW-0. In an in vitro cytotoxicity analysis, PLW-0 and PLE-0 (up to $1,000{\mu}g/m{\ell}$) did not affect the growth of peritoneal macrophages and Colon 26-M3.1 carcinoma cells. In contrast, they enhanced lymphocyte proliferation activity. Peritoneal macrophages stimulated with PLW-0 and PLE-0 produced various cytokines, such as IL-6 and IL-12. However, PLE-0 was more effective on the cytokine production. Intravenous administration of PLW-0 and PLE-0 significantly augmented natural killer (NK) cell cytotoxicity against Yac-1 tumor cells 3 days after the treatment of polysaccharide fractions. But NK cells obtained from the PLE-treated group showed higher tumoricidal activity even at a low dose of $40{\mu}g$/mouse. In experimental lung metastasis of Colon 26-M3.1 carcinoma cells, prophylactic administration of PLW-0 and PLE-0 significantly inhibited lung metastasis in a dose-dependent manner and PLE-0 was more effective on the inhibition of cancer metasasis. The results lead us to conclude that the pectinase-treated process is indispensable to preparing polysaccharides with higher immune-stimulating activity from persimmon leaves.

• Journal of Chest Surgery
• /
• v.12 no.4
• /
• pp.324-335
• /
• 1979

During the period of 4 years from August 1975 to August 1979 one hundred and forty seven cases of lung cancer were seen at Paik Foundation Hospital in Seoul, Korea. Among these 147 cases, 104 patients had primary carcinoma of the lung and the remainder was metastatic carcinoma to the lung. Among these 104 primary carcinoma patients, 73 cases were proven histologically as primary carcinoma of the lung. There were three cases of alveolar cell carcinoma [Table 1 ]. This clinical observation is based on those 73 cases including three case reports of the alveolar cell carcinoma. 1. Peak incidence was observed in the 5th decade of life. Male to female ratio was 2 to 1 [Fig. 1]. 2. Pathological classifications were as follows: epidermoid carcinoma, 24 cases [32.9%]; undifferentiated carcinoma, 20 cases [27.4%]; adenocarcinoma, 15 cases [20.5%]; bronchioloalveolar carcinoma [5.5%] and positive cytology, 10 cases [13.7%] [Fig. 2]. 3. Evidence of inoperability was observed in 55 patients [75% of the 73 cases] [Table 3]. 4. Among those 73 cases, operability was evaluated in 18 patients or 25%. One patient refused operation and 17 patients [23.6%] were explored. In 11 [15%] out of 17 patients, thoracotomies were performed. Six cases were pneumonectomies and 5 cases were lobectomies or bilobectomies [Fig. 3]. 5. First case of alveolar cell carcinoma was a 46 year-old housewife complaining of cough and hemoptysis for one year. The plain chest X-ray and bronchogram showed characteristic pictures as Figures 4 and 5. A pneumonectomy was carried out. Histologically, a beautiful alveolar carcinoma consisted of the characteristic tall columnar epithelial cells, which were lining the alveolar spaces as seen in Figures 6, 7, 8, and 20. 6. In the second case of 41 year old male, predominant clinical feature was single, well defined mass in the right lower lobe [Fig. 10 and 11] on chest X-ray. Bilobectomized specimen showed fragile, soft and hard tissue containing mucoid secretions and focal yellowish necrosis with pigmentation on cut surface [Fig. 12]. Slides showed tumor cells lined up along the alveolar septa with papillary projections [Fig. 13 and 14]. 7. Third case of alveolar cell carcinoma was a 50-year-old housewife with hemoptysis. An outstanding clinical picture was a round to lobulated mass in the right upper lobe [Fig. 16]. She is living now, 2 years and 1 month post-operatively, but has arrived at terminal stage with military nodular disseminations to the contralateral lung [Fig. 19].