• Clinical Endoscopy
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• v.56 no.4
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• pp.470-478
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• 2023

Background/Aims: Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. Methods: Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary's Hospital. Results: A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan-Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53-11.40) The histological types of MGN were not related to the primary histology types. Conclusions: MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.315-325
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• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Clinical Endoscopy
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• v.55 no.6
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• pp.775-783
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• 2022

Background/Aims: Colorectal endoscopic submucosal dissection (ESD) is burdened by its associated high risk of adverse events and long procedure time. Recently, a waterjet-assisted knife was introduced to simplify and speed up the procedure. The aim of this study was to evaluate the efficacy and safety of waterjet-assisted ESD (WESD) compared to that of the conventional ESD (CESD) technique. Methods: The charts of 254 consecutive patients who underwent colorectal ESD between January 2014 and February 2021 for colorectal neoplasms were analyzed. The primary outcome was the en-bloc resection rate. Secondary outcomes were complete and curative resection rates, the need to switch to a hybrid ESD, procedure speed, the adverse event rates, and the recurrence rates. Results: Approximately 174 neoplasias were considered, of which, 123 were removed by WESD and 51 by CESD. The en-bloc resection rate was higher in the WESD group (94.3% vs. 84.3%). Complete resection rates and curative resection rates were similar. The need to switch to a hybrid ESD was greater during CESD (39.2% vs. 13.8%). Procedure speed and adverse event rates were similar. During follow-up, one recurrence occurred after a WESD. Conclusions: WESD allows a high rate of en-bloc resections and less frequently requires a rescue switch to the hybrid ESD compared to CESD.

• Journal of Gastric Cancer
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• v.6 no.2
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• pp.109-113
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• 2006

Purpose: Various minimally invasive surgical techniques, such as an endoscopic mucosal resection and a laparoscopic gastrectomy, are becoming common practice for some cases of early gastric cancer (EGC) defined in terms of the depth of invasion being limited to the mucosa or submucosa. However, there are rare cases of early gastric cancer with massive lymph-node metastasis. Materials and Methods: From 6 university hospitals of Korea, 2,772 EGC cases were resected during the various period of analysis (1,432 cases of mucosal cancer and 1,340 of submucosal cancer). Results: As control data, we used the data from a single institute, CHA University Hospital. There were nine cases of early gastric cancer (9/2,772, 0.32%) with N3 lymph node metastasis defined by more than 15 lymph nodes being metastasized according to the UICC-TNM classification (pT1N3, stage IV). Two cases were mucosal cancer (2/1,432, 0.1 4%), and seven cases were submucosal cancer (7/1,340, 0.52%). Metastasized lymph nodes varied in number from 18 to 52. There were three male and six female patients with a mean age of 57. This is a totally reversed sex ratio compared to the usual gastric cancer or EGC. Among the total of 9 EGC patients, there were 5 who had superficial spreading carcinomas with surface areas larger than $25\;cm^2$. This is a significantly higher proportion compared to the general EGC population. When we compared the tumor size according to the LN status, the N3 group was definitely larger than the other groups. 78% of the pT1N3 cases showed lymphatic invasion, which is very high compared to the 4.7% in general EGC cases. Among the 9 cases, 6 patients had too short a follow-up period to evaluate the correct prognosis, but there was one patient with a non-curative resection and two patients with early recurrence. Although the sample size is small and the follow-up period is short, we can expect a very poor prognosis when we consider the common prognosis of EGC that is widely known and accepted. Conclusion: From these results, we can a conclude that the risk factors for pT1N3 gastric cancer are female patients, submucosal invasion, larger tumor size, and lymphatic invasion. However rare, the existence of pT1N3 gastric cancer needs to be taken into consideration, especially during the diagnosis. Furthermore, minimally invasive treatment for EGC needs to be chosen with great precaution. Since the prognosis of pT1N3 gastric cancer is expected to be poor, aggressive adjuvant chemotherapy may be necessary. (J Korean Gastric Cancer Assoc 2006;6:109-113)

• Tuberculosis and Respiratory Diseases
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• v.53 no.5
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• pp.542-549
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• 2002

Purpose : The purpose of our study was to assess the usefulness of the Tl-201 SPECT for the detection of the postoperative tumor recurrence on chest wall. Methods: 28 patients including 14 with suspected recurrence of tumor in the chest wall on postoperative chest cr scan, 10 with postoperative pleural effusion which proved benign on radiologic, cytologic and laboratory findings, and 4 with chronic tuberculous empyema as control group were included. All patients underwent SPECT 30 minutes and 4 hours after intravenous injection of 111MBq of Tl-201. Tumor uptake was visually graded by two interpreters and scored as follows : no uptake:0, similar to contralateral lung: 1, higher than contralateral lung but less than heart:2 and similar to heart:3. Results : Markedly increased (grade 3 or 2) Tl-201 uptake was noted in patients with suspected recurrence of tumor in the chest wall (13/14) whereas no (8/10) or minimal (2/10) uptake along the collapsed lung in patients with postoperative benign pleural effusion. In two patients, Tl-201 SPECT revealed additional recurrent tumor mass lesions that were barely perceptible on chest cr scan. Patients with chronic tuberculous empyema showed relatively smoothly marginated increased uptake along the chest wall 4/4), but lesser in degree (grade 1 or 2), when compared to recurrent tumor uptake. Conclusion : Tl-201 lung SPECT seems to be useful to detect postoperative tumor recurrence on chest wall and to differentiate malignant from benign pleural effusion and may provide additional information to the morphologic data obtained by CT.

• The Korean Journal of Nuclear Medicine
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• v.39 no.5
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• pp.269-277
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• 2005

Purpose: This study evaluated the diagnostic value of $^{18}F-FDG$ PET/CT in detecting cervical lymph node metastases in head and neck cancer patients. Materials & Methods: The patients were divided into two groups, 46 patients underwent PET/CT scan for initial staging before surgery, and 20 patients for restaging of recurrence after primary treatment. Increased FDG uptakes in cervical lymph nodes were evaluated retrospectively and correlated with the histopathologic results. Results: In the initial staging group, 21 lymph nodes were detected by PET/CT in 15 patients. 20 lymph nodes were confirmed as metastases with a mean peak SUV of 5.84, and the remaining one lymph node was an inflammatory lesion, with a peak SUV of 2.75. Seven metastatic lymph nodes were reported only by histopatholoay. The sensitivity, specificity, positive predictive value and negative predictive value were 74.0%, 99.6%, 95.2% and 97.3%, respectively. In the recurrence group, 11 lymph nodes were detected in 9 patients, and 8 nodes were true positive, with a mean peak SUV of 5.65. The other three were inflammatous lymph nodes, and the peak SUVs were 2.16, 2.94 and 3.53. One false negative lymph node was reported. The sensitivity, specificity, positive predictive value and negative predictive value were 88.8%, 97.7%, 72.7% and 92.9%, respectively. Conclusions: FDG-PET/CT shows higher positive predictive value in the initial staging group, and better sensitivity in the recurrence group. Therefore PET/CT could be useful for both initial staging and restaging of recurrent cervical lymph node metastases.

• Journal of Chest Surgery
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• v.32 no.9
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• pp.799-805
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• 1999

Background: Leakage, stricture formation, and tumor recurrence at the anastomotic site are serious problems after esophagectomy for cancer of the esophagus or cardia. The prevalence of these postoperative complications may be affected by whether an anastomosis is made in the neck or in the chest, therefore a comparison was made between anastomoses made at these two sites. Material and Method: Between 1987 and 1998, 36 patients with cancer of the esophagus underwent transthoracic esophagectomy with cervical(NA, n=20) or thoracic anastomosis(CA, n=16). The tumors were staged postoperatively(stage IIA, n=13; s tage IIB, n=7; stage III, n=16) and were located in the middle thoracic(n=22) or lower thoracic esophagus and cardia(n=14). Result: The overall operative mortality was 8.3%(5% for NA group, 12.5% for CA group). The anastomotic leak rate for the NA group was 15.0% and 12.5% for the CA group. The anastomotic leak rate differed according to the manual(27.3%) or stapled(8.0%) techniques(p < 0.05). The median proximal resection margins in the NA and CA groups were 9.6 cm and 5.8 cm, and the corresponding rates of anastomotic tumor recurrence were 5.3% and 28.6%(p < 0.05). The prevalence of benign stricture formation (defined as moderate/severe dysphagia) was higher in the NA group(36.8%) than in the CA group(21.4%). When an anastomosis was made by the stapled technique, smaller size of the staple increased the prevalence of stricture formation - 41.7% with 25-mm staple and 9.1% with 28-mm staple(p < 0.05). Conclusion: Wider resection margin could decrease the anastomotic tumor recurrence, and the stapled technique could decrease the anastomotic leak. The prevalence of benign stricture was higher in the cervical anastomosis but the anastomotic leak and smaller size(25-mm) of the staple should be considered as risk factors.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.169-173
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• 2001

Objectives: The p53 tumor suppressor gene encodes a nuclear transcription factor that is critical regulator of cell growth and proliferation through its action in cell-cycle checkpoint control. The wide variety of stressful stmuli which include DNA damage, hypoxia, heat shock, metabolic changes activate the p53 protein, which in turn drives a series of events that culminate either in cell cycle arrest or apoptosis. Mutations of the p53 gene is the most common genetic alteration in human cancer. This gene is altered in approximately 40-60% of head and neck cancers. Whereas the wild-type form of the p53 protein plays a central role in cell-cycle control in response to DNA damage, most of the mutant forms are unable to do so. The high levels of p53 protein expression in tissues are related to the increased cellular proliferative activity and may be associated with the poor clinical outcome. To determine whether the expression of the p53 protein has prognostic significance and is associated with patterns of treatment failure in head and neck squamous cell carcinoma (HNSCC), We analyzed p53 overexpression in 40 cases of HNSCC. Materials and Methods: Immunohistochemical analysis with a monoclonal antibody (DO7) specific for p53 protein was used to detect expression of the protein in formalin-fixed, paraffin-embedded tumor samples from 40 HNSCC. We evaluated p53 protein expression and analyzed the relationship between the p53 overexpression and age, sex, primary tumor site, stage, survival rate, recurrence. All reported P values resulted from two-sided statistical tests. Results: Overexpression of p53 was detected in 20 cases(50%) among 40 cases of HNSCC. The p53 overexpression was not associated with age, sex, primary tumor site, stage, recurrence and survival rate. Conclusions: In our results, p53 was not significant prognostic factor in HNSCC. Based on many previous studies, It is evident that p53 has a certain role in tumorigenesis of HNSCC. So, the further study is needed to evaluate the prognostic significance of p53 in HNSCC.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.205-209
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• 2001

Purpose: Most cases of primary hyperparathyroidism are due to parathyroid adenoma or parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause of hyperparathyroidism. Although the diagnosis of parathyroid carcinoma is usually established by pathologic criteria especially of vascular or capsular invasion, some clinical and biochemical features differentiate it from benign forms of hyperparathyroidism. We under-took a retrospective study in 6 patients with parathyroid carcinoma, with the aim of conveying experience from management for this rare cause of hyperparathyroidism. Methods: Clinical symptoms, biochemical laboratory, radiologic, and intraoperative findings, local recurrence and distant metastasis were analyzed in 6 patients diagnosed pathologically as a parathyroid carcinoma after operation from 1992 to 2001. Results: Mean age was 50.2 years (33.0-60.0 years) and male to female ratio was 1:1. Neck mass was found in 5 patients, multiple bone pain in 3 patients and renal stone in 1 patient. One case has suffered from chronic renal failure for 19 years. Although preoperative laboratory evaluations showed the aspects of hyperparathyroidism in all cases, mean serum calcium level was 11.2mg/dl(10.5-12.1mg/dl), slightly elevated. Laboratory values after surgery were within the normal range in 5 cases. However, in one case with chronic renal failure, serum PTH levels, serially checked, were above the normal range. Any of imaging methods failed to suggest a parathyroid carcinoma preoperatively. Parathyroid adenoma was suspected in 3 cases, thyroid cancer in the other cases before surgery. The extent of resection was radical resection of parathyroid lesion with more than unilateral thyroid lobectomy and central compartment neck node dissection and in 2 cases, the resection of recurrent laryngeal nerve or strap muscles was added. During follow-up period, any local or systemic recurrence were not evident in all the cases. Conclusion: Although parathyroid carcinoma is a rare disease and its preoperative diagnosis, in our experience, could not easily be made, the understanding of characteristic clinical and biochemical feature could help diagnosis at first surgery. Radical resection without remaining residual tumor is most important for the management of the parathyroid cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6493-6499
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• 2013

Background: Non-epithelial malignant ovarian tumors and clear cell carcinomas, Brenner tumors, transitional cell tumors, and carcinoid tumors of the ovary are rare ovarian tumors (ROTs). In this study, our aim was to determine the clinicopathological features of ROT patients and prognostic factors associated with survival. Materials and Methods: A total of 167 patients with ROT who underwent initial surgery were retrospectively analyzed. Prognostic factors that may influence the survival of patients were evaluated by univariate and multivariate analyses. Results: Of 167 patients, 75 (44.9%) were diagnosed with germ-cell tumors (GCT) and 68 (40.7%) with sex cord-stromal tumors (SCST); the remaining 24 had other rare ovarian histologies. Significant differences were found between ROT groups with respect to age at diagnosis, tumor localization, initial surgery type, tumor size, tumor grade, and FIGO stage. Three-year progression-free survival (PFS) rates and median PFS intervals for patients with other ROT were worse than those of patients with GCT and SCST (41.8% vs 79.6% vs 77.1% and 30.2 vs 72 vs 150 months, respectively; p=0.01). Moreover, the 3-year overall survival (OS) rates and median OS times for patients with both GCT and SCST were better as compared to patients with other ROT, but these differences were not statistically significant (87.7% vs 88.8% vs 73.9% and 170 vs 122 vs 91 months, respectively; p=0.20). In the univariate analysis, tumor localization (p<0.001), FIGO stage (p<0.001), and tumor grade (p=0.04) were significant prognostic factors for PFS. For OS, the univariate analysis indicated that tumor localization (p=0.01), FIGO stage (p=0.001), and recurrence (p<0.001) were important prognostic indicators. Multivariate analysis showed that FIGO stage for PFS (p=0.001, HR: 0.11) and the presence of recurrence (p=0.02, HR: 0.54) for OS were independent prognostic factors. Conclusions: ROTs should be evaluated separately from epithelial ovarian cancers because of their different biological features and natural history. Due to the rarity of these tumors, determination of relevant prognostic factors as a group may help as a guide for more appropriate adjuvant or recurrent therapies for ROTs.