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ABSTRACT: Currently, serum biomarkers, which are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinoma do not exist. Therefore, this study identified a panel of serum biomarkers for the diagnosis of gastric adenocarcinoma.
A 29-plex array platform with 29 biomarkers, consisting of 11 proteins discovered through proteomics and 18 previously known to be cancer-associated, was constructed. A test/training set consisting of 120 gastric adenocarcinoma and 120 control samples were examined. After 13 proteins were selected as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 95 gastric adenocarcinoma and 51 control samples.
Epidermal growth factor receptor (EGFR), pro-apolipoprotein A1 (proApoA1), apolipoprotein A1, transthyretin (TTR), regulated upon activation, normally T-expressed and presumably secreted (RANTES), D-dimer, vitronectin (VN), interleukin-6, α-2 macroglobulin, C-reactive protein and plasminogen activator inhibitor-1 were selected as classifiers in the two algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (>88%). These algorithms also accurately classified in the validation set (>85%).
Two panels of combinatorial biomarkers, including EGFR, TTR, RANTES, and VN, are developed, which are less invasive method for the diagnosis of gastric adenocarcinoma. They could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy.
British Journal of Cancer 02/2012; 106(4):733-9. · 5.04 Impact Factor
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ABSTRACT: A MEMS-scale nonlinear resonator for ultra wide-bandwidth (UWB) energy harvesting applications has been designed and fabricated. Ambient vibration with a varying frequency spectrum is converted directly to electricity via the piezoelectric effect. Unlike most energy harvesters reported, our design utilizes the tensile stretching strain in a doubly-anchored beam [1, 2]. This stretching results in a nonlinear stiffness which provides a passive feedback and consequently a Duffing mode resonance. The doubly-anchored beam structure stores the majority of the strain energy in non-linear stretching and behaves like a frequency locked loop device. This enables the beam's resonance frequency to track the external vibration frequency until it reaches a point of instability. This paper describes the design, fabrication, and performance of this new energy harvesting device which facilitates this nonlinear vibration mode for small environmental vibrations.
Micro Electro Mechanical Systems (MEMS), 2011 IEEE 24th International Conference on; 02/2011
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ABSTRACT: The pattern of gastric cancer in the Western world is changing, with an increased proportion of tumours in the upper stomach. The aim of this study was to investigate changes in clinicopathological features and survival of patients with resected gastric cancer at a single institution, in an area of high incidence in the Far East.
Clinical features and pathological findings were compared in patients with gastric cancer who underwent gastrectomy at Seoul National University Hospital during four consecutive periods (1986-1990, 1991-1995, 1996-2000 and 2001-2006).
There were 12 026 patients. The mean age increased from 53·4 years in the first period to 57·4 years in the last (P < 0·001). The proportion of patients aged 70 years or older also increased, reaching 16·1 per cent in the final period. Upper-third cancer increased from 5·3 per cent in the first period to 14·0 per cent in the fourth (P < 0·001). Early gastric cancer (pathological T1) increased continuously over the four time intervals, from 24·8 to 48·9 per cent (P < 0·001). The overall 5-year survival rate increased from 64·0 per cent in the first period to 73·2 per cent at the end (P < 0·001), and this survival improvement was apparent in patients aged 40 years or more.
The mean age of patients with gastric cancer has increased during the past 20 years. The proportion of early gastric cancer and overall survival have gradually increased, especially in patients aged over 40 years.
British Journal of Surgery 11/2010; 98(2):255-60. · 4.61 Impact Factor
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ABSTRACT: This study aimed to determine the appropriate extent of lymph node (LN) dissection in gastric cancer by analysing LN metastasis patterns from prospectively collected topographical data on nodal status at Seoul National University Hospital, Korea.
The metastasis rate for each LN station was analysed according to the depth of tumour invasion in patients with primary lower-third gastric cancer who underwent curative gastrectomy. The Maruyama Index of unresected disease (MI) was calculated using the WinEstimate(®) program with simulation of various extents of LN dissection.
LN metastasis in mucosal cancer was rare; 2·6 per cent of patients had a MI of more than 5 with simulation of D1 plus station 7 dissection, whereas 0·9 per cent had a MI above 5 with D1 plus stations 7 and 8a. In submucosal cancer, 3·3 per cent of tumours metastasized to level 2 LN stations outside the range of D1 plus stations 7, 8a and 9. The proportion of patients with a MI above 5 was 9·0 per cent with D1 plus stations 7, 8a and 9 dissection. The nodal metastasis rate was higher at level 1 and 2 for muscularis propria or deeper cancers.
D1 dissection plus stations 7 and 8a for mucosal cancer, and D2 dissection for cancers of the muscularis propria or deeper seems appropriate. For submucosal cancer, an expanded dissection to the D2 level should be considered to ensure complete removal of metastatic LNs.
British Journal of Surgery 10/2010; 98(1):65-72. · 4.61 Impact Factor
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K W Lee,
S M Bang,
S Kim, H J Lee,
D Y Shin,
Y Koh,
Y G Lee,
Y Cha,
Y J Kim,
J H Kim,
D J Park,
H H Kim,
D Oh,
J S Lee
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ABSTRACT: Data on venous thromboembolism (VTE) in gastric cancer (GC) are very scarce.
To investigate the incidence, risk factors and prognostic implications of VTE in Asian GC patients.
Prospective databases containing clinical information on GC patients (n = 2,085) were used.
The 2-year cumulative incidences of all VTE events were 0.5%, 3.5% and 24.4% in stages I, II-IV(M0) and IV(M1), respectively. Advanced stage, older age and no major surgery were independent risk factors for developing VTE. When the VTE cases were classified into extremity venous thrombosis (EVT), pulmonary thromboembolism (PTE) or intra-abdominal venous thrombosis (IVT), IVTs (62%) were more common than EVTs (21%) or PTEs (17%). Although peri-operative pharmacologic thromboprophylaxis was not routinely administered, the VTE incidence after major surgery was only 0.2%. During chemotherapy, EVT/PTE developed more frequently than IVT (54% vs. 19%); however, during untreated or treatment-refractory periods, IVT developed more frequently than EVT/PTE (69% vs. 36%). In multivariate models, the development of EVT/PTE was a significant predictor of early death when compared with no occurrence of VTE (P < 0.05). However, IVT did not affect survival.
This is the largest study that specially focused on VTE in GC and the VTE incidence in Asian GC patients was first demonstrated. Considering the low incidence of post-operative VTE development, the necessity of peri-operative pharmacologic thromboprophylaxis should be evaluated separately in Asian patients. The clinical situation of the development of EVT/PTE and IVT differed. Only EVT/PTE had an adverse effect on survival and IVT had no prognostic significance.
Journal of Thrombosis and Haemostasis 03/2010; 8(3):540-7. · 5.73 Impact Factor
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ABSTRACT: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely performed. Indications for these procedures have been extended in Korea and Japan. The aim was to evaluate whether these extended indications are safe.
All patients who had surgery for early gastric cancer at Seoul National University Bundang Hospital between May 2003 and December 2007 were identified from a prospective database. Lymph node status was examined in patients who met extended indications for EMR and had undergone surgical resection.
Of patients with mucosal cancers, 129 met extended indications for EMR or ESD and three (2.3 per cent) had lymph node metastasis. Of the 52 submucosal cancers meeting extended indications for EMR or ESD, two (4 per cent) had lymph node metastasis. Differentiated mucosal cancers without ulcer formation did not have lymph node metastasis, irrespective of size.
Extending the indications for EMR and ESD according to the Japanese Gastric Cancer Association guidelines carries an increased risk of lymph node metastasis. For cancers meeting these criteria, treatment by gastric resection with lymph node dissection should still be considered. A well differentiated mucosal cancer of any size without ulceration may be considered as an extended indication for EMR or ESD.
British Journal of Surgery 09/2009; 96(10):1157-61. · 4.61 Impact Factor
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J W Kim,
S-J Kim,
Y-H Chung,
J-H Kwon, H-J Lee,
Y-J Chung,
Y J Kim,
Do-Youn Oh,
S-H Lee,
D-W Kim,
S-A Im,
T-Y Kim,
D S Heo,
Y-J Bang
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ABSTRACT: To understand patients' perceptions of clinical trials (CTs) is the principal step in the enrollment of patients to CTs. However, these perceptions in eastern countries are very rare. From 12 February 2007 to 13 April 2007, we consecutively distributed the questionnaire to 842 cancer patients who initiated a first cycle of chemotherapy regardless of each treatment step in the Seoul National University Hospital. Younger age, higher educational degree, higher economic status, and possession of private cancer insurance were related with significantly higher awareness of CTs (P=0.001, P=0.006, P=0.002, and P=0.009, respectively). However, unlike awareness, perceptions on benefits of CTs were not changed according to age, educational degree, and economic status (P=0.709, P=0.920, and P=0.847, respectively). Willingness was also not changed according to age, educational degree, economic status, and private cancer insurance (P=0.381, P=0.775, P=0.887, and P=0.392, respectively). Instead, males and heavily treated patients had more positive perceptions on benefits (P=0.002 and P=0.001, respectively) and more willingness to participate in CTs (OR=1.17, 1.14-2.75: OR=1.59, 1.01-2.51, respectively). In summary, cancer patients' awareness of CTs, perceptions on the benefit in CTs, and willingness to participate are differently influenced by diverse medical and social conditions. This information would be very helpful for investigators to properly conduct CTs in eastern cancer patients.
British Journal of Cancer 12/2008; 99(10):1593-9. · 5.04 Impact Factor
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ABSTRACT: To evaluate the feasibility and accuracy of sentinel node (SN) biopsy for gastric cancer.
One hundred patients with gastric cancer diagnosed as cT1 (n=80) or cT2a (n=20) were enrolled. Indocyanine green-stained SNs were analysed by hematoxylin and eosin staining (n=100) and by cytokeratin immunohistochemistry (n=50).
SNs were identified in 94 of the 100 patients and the mean number of SNs was 4.4 (range, 1-12). Of these 94 patients, 14 patients had lymph node metastases. Two patients with T1 and one patient with T2 had metastases in non-SNs alone by hematoxylin and eosin staining (diagnostic accuracy =97.3% in T1 and 95.0% in T2). All three patients with a false negative result had a tumour, which was more than 4 cm in size and signet ring cell histology. In two of them, the tumour was located at lesser curvature. By immunohistochemical staining, three patients with T1 and one patient with T2 were found to have lymph node micrometastases in non-SNs alone among 45 patients (diagnostic accuracy =92.1% in T1, 85.7% in T2).
SN biopsy using indocyanine green can be performed rapidly and easily with a high detection rate and accuracy in patients with T1 gastric cancer. However, it should be performed with caution for large tumours with a signet ring cell histology located at lesser curvature due to the possibility of a false negative result.
European Journal of Surgical Oncology 03/2006; 32(1):48-54. · 2.50 Impact Factor
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ABSTRACT: Few reports are available on the use of intraoperative gastroscopy for gastric surgery.
The details of 33 patients (25 early gastric cancers and eight gastric submucosal tumors) who underwent intraoperative gastroscopy from June 2003 to June 2004 were analyzed. The type of operation or resection margin was determined by evaluating both sides of the stomach simultaneously by combined operative and gastroscopic methods.
Preoperative endoscopic clipping was done preferentially for early gastric cancer. However, when precise localization was needed, intraoperative gastroscopy was used. Curative gastric resection was possible in 25 early gastric cancer patients after accurate lesion localization. Laparoscopic wedge resections of submucosal tumors were performed in seven patients without stenosis by combined laparoscopic and gastroscopic methods.
Intraoperative gastroscopy can be used effectively during gastric surgery for early gastric cancer or submucosal tumors and can be regarded as a modern stethoscope to gastric surgeons.
Surgical Endoscopy 11/2005; 19(10):1358-61. · 4.01 Impact Factor
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ABSTRACT: The aim of this study was to identify factors that predict morbidity and mortality in gastric cancer surgery.
Data on 719 consecutive patients who underwent operations for gastric cancer at Seoul National University Hospital between January and December 2002 were reviewed.
Overall morbidity and mortality rates were 17.4 per cent (125 patients) and 0.6 per cent (four patients) respectively, and the rates of surgical and non-surgical complications were 14.7 per cent (106 patients) and 3.3 per cent (24 patients). Morbidity rates were higher in patients aged over 50 years (odds ratio (OR) 1.04 (95 per cent confidence interval (c.i.) 1.02 to 1.06)), when the gastric tumour was resected with another organ (36 per cent for combined resection versus 15.4 per cent for gastrectomy only; OR 3.25 (95 per cent c.i. 1.76 to 6.03)) and when gastrojejunostomy was used for reconstruction after subtotal gastrectomy (17.0 per cent for Billroth II versus 9.5 per cent for Billroth I; OR 2.00 (95 per cent c.i. 1.05 to 3.79)). Only three patients (2.8 per cent) with a surgical complication underwent reoperation, two for adhesive obstruction and one for intra-abdominal bleeding.
Age, combined resection and Billroth II reconstruction after radical subtotal gastrectomy were independently associated with the development of complications after gastric cancer surgery.
British Journal of Surgery 10/2005; 92(9):1099-102. · 4.61 Impact Factor
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ABSTRACT: Transforming growth factor-beta (TGF-beta) modulates the growth and function of many cells, including those with malignant transformation. Smad proteins have been identified as major components in the intracellular signaling of TGF-beta family members.
To clarify the correlations between clinicopathologic profiles and the patient's survival, the expression of common mediator Smad (Smad4) and inhibitory Smad (Smad7) were evaluated immunohistochemically in 304 consecutive gastric carcinomas using the tissue array method.
Positive Smad4 expression was observed in 266 (87.5%) tumors and positive Smad7 expression in 98 (32.2%) tumors. The prognosis of patients with a Smad4-positive tumor was significantly better than that of the patients with a negative tumor. The survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. In subgroup analysis according to TNM (tumour-node-metastasis) stage, both Smad4 and Smad7 showed most significant prognostic differences in stage I gastric cancer patients. Multivariate analysis indicated that tumor size, depth of invasion, lymph node metastasis and Smad7 expression were independent prognostic factors.
Enhanced expression of the TGF-beta signaling inhibitor Smad7 may present one of the novel mechanisms of TGF-beta resistance in human gastric carcinomas.
Annals of Oncology 05/2004; 15(4):574-80. · 6.43 Impact Factor
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ABSTRACT: Transcriptional repression of the TGF-beta type II receptor (RII) is one of the mechanisms leading to TGF-beta resistance. The newly identified epithelium-specific ets transcription factor ERT/ESX/ESE-1 binds to the TGF-beta RII promoter and induces promoter activity. This study aims to investigate the mechanisms underlying development of ERT-mediated TGF-beta resistance using antisense ERT oligonucleotide. We performed Northern blot analysis of TGF-beta RII expression in human colon cancer cell line, RKO, after transfecting these cells with MFG-antisense-ERT retroviral construct. The plasmid containing the chloramphenicol acetyltransferase (CAT) gene alone was used as the control. The amount of TGF-beta RII mRNA appears to be poor in RKO cells expressing antisense ERT compared with both parental RKO and control cells. In conclusion, transfection of MFG-antisense-ERT construct into the colon cancer cell line could result in lower levels of TGF-beta RII mRNA expression, which means that ERT mediates the expression of TGF-beta RII and the transcriptional inhibition of ERT could be a one of the mechanisms of colonic carcinogenesis. More in vitro and in vivo studies should be required to evaluate this treatment in clinical setting.
Journal of experimental & clinical cancer research: CR 10/2003; 22(3):477-80. · 1.50 Impact Factor
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Transplantation Proceedings 12/2002; 34(7):2799-800. · 1.00 Impact Factor
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ABSTRACT: Several clinical studies have focused on the therapeutic effects of interferon gamma (IFN-gamma) in patients with severe atopic dermatitis (AD), although the dosage of recombinant IFN-gamma (rIFN-gamma), therapeutic schedule, and the degree of clinical improvement were different among studies. Although the exact mechanism of action of IFN-gamma therapy in AD is not clear, the beneficial effects of IFN-gamma have been attributed mainly to an immunomodulating effect on the expression of certain immunologic markers.
Our purpose was to study the therapeutic effect of two different dosages of rIFN-gamma on AD and to investigate the change of lesional expression of infiltrating inflammatory cell markers associated with rIFN-gamma therapeutic efficacy.
Fifty-one patients with severe recalcitrant AD were treated with rIFN-gamma. Twenty patients were treated with 0.5 x 10(6) IU/m(2) of rIFN-gamma (low-dose [LD] group); 21 patients received 1.5 x 10(6) IU/m(2) of rIFN-gamma (high-dose [HD] group); and 10 patients received placebo. The patients were injected subcutaneously 3 times a week for 12 weeks. Immunohistochemical study was performed in 20 patients of the HD group in the initial visit and after completion of rIFN-gamma therapy with a panel of 14 monoclonal antibodies as markers of inflammatory cells and cytokines.
The disease severity of the 2 groups treated with rIFN-gamma was reduced significantly at the end of treatment compared with that of the placebo group (P<.05). More rapid clinical improvement and more effective treatment outcome were seen in the HD group than in the LD group for the initial 6-week treatment period; however, the clinical improvement in both of the treated groups was stable and maintained after week 8 of treatment. Immunohistochemical findings showed statistically significant reduction in the lesional expression of CD25 and EG2 cells that infiltrated into skin after rIFN-gamma therapy.
This study demonstrated that rIFN-gamma therapy for AD is safe and effective. In the early phase of therapy, a higher dosage of rIFN-gamma is more effective; and for the maintenance of clinical improvement, a lower dosage of rIFN-gamma is recommended when high cost and effectiveness of rIFN-gamma are considered. The therapeutic efficacy of rIFN-gamma in AD might be in part related to the decreased number of CD25(+) and EG2(+) inflammatory cells infiltrated into skin.
Journal of the American Academy of Dermatology 06/2000; 42(6):1033-40. · 3.99 Impact Factor
