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Korea

Cancer Statistics
Population in 2012: 48.6m
People newly diagnosed with cancer (excluding NMSC) / yr: 219,500
Age-standardised rate, incidence per 100,000 people/yr: 307.8
Risk of getting cancer before age 75:29.3%
People dying from cancer /yr: 81,500
Data from IARC GlobalCan (2012)
Korean Cancer Organisations and Resources
Latest Research Publications Related to Republic of Korea

Korean Cancer Organisations and Resources (13 links)


Latest Research Publications Related to Republic of Korea

Hong KD, Um JW, Min BW, et al.
Lymph Node Micrometastasis Cannot Be Considered as Positive Lymph Node in Nonmetastatic Colorectal Cancer.
Am Surg. 2017; 83(2):127-133 [PubMed] Related Publications
The prognostic value of micrometastasis in colorectal cancer (CRC) remains controversial. The study investigated whether lymph node (LN) micrometastasis can have prognostic value in CRC as compared with macrometastasis. The study included 488 patients with curatively resected stage I, II, or III CRC treated between 2004 and 2011. Immuohistochemical staining with monoclonal antibody CAM 5.2 was performed on negative LNs by hematoxylin-eosin staining. The prognostic value of LN micrometastasis was investigated in multivariate analysis. Regression analysis was performed to identify a causal relationship between micro- and macrometastasis. Survival differences were compared between conventional N staging and hypothetic N staging taking micrometastasis in the positive node. A total of 93 patients (19.1%) showed LN micrometastasis. Patients with micrometastasis had more advanced tumor characteristics in terms of tumor size, grade, T stage, N stage, lymphatic invasion, and vascular invasion. In multivariate analysis, micrometastasis was not related with recurrence. Preoperative carcinoembryonic antigen level, neural invasion, and macrometastasis were independent risk factors in the analysis. Regression analysis showed that there was not a causal relationship between micro- and macrometastasis (R2 = 0.004, P = 0.153). When the cumulative numbers of micro- and macrometastatic LNs were calculated together, the discriminative power of survival difference between each node stage became less prominent, compared with conventional N staging. LN micrometastasis is related with advanced tumor characteristics, but does not reflect poor prognosis in nonmetastatic CRC. Micrometastasis cannot be considered as positive LN to predict poor prognosis.

Kim SH, Kang JG, Kim CS, et al.
Doxorubicin has a synergistic cytotoxicity with cucurbitacin B in anaplastic thyroid carcinoma cells.
Tumour Biol. 2017; 39(2):1010428317692252 [PubMed] Related Publications
In this study, the combined effect of doxorubicin with cucurbitacin B on survival of anaplastic thyroid carcinoma cells was evaluated. For experiments, 8505C and CAL62 human anaplastic thyroid carcinoma cells were used. Cell viability, the percentage of viable cells, and cytotoxic activity were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, multiplexed cytotoxicity assay, and cytotoxicity assay, respectively. Reactive oxygen species production was measured. In experiments, doxorubicin and cucurbitacin B reduced cell viability in a dose- and time-dependent manner. Cotreatment of doxorubicin and cucurbitacin B, compared with treatment of doxorubicin alone, decreased the percentage of viable cells and increased cytotoxic activity. All of the combination index values were lower than 1.0, suggesting the synergism between doxorubicin and cucurbitacin B in induction of cytotoxicity. In cells treated with both doxorubicin and cucurbitacin B, compared with doxorubicin alone, the protein levels of cleaved poly(adenosine diphosphate-ribose) polymerase and cyclooxygenase 2 and reactive oxygen species production were enhanced. In contrast, the protein levels of B-cell chronic lymphocytic leukemia/lymphoma 2 and survivin and B-cell chronic lymphocytic leukemia/lymphoma 2/B-cell chronic lymphocytic leukemia/lymphoma 2-associated x protein ratio were diminished. The protein levels of Janus kinase 2 and signal transducer and activator of transcription 3 were reduced, while phospho-extracellular signal-regulated kinase 1/2 protein levels were elevated without change in total extracellular signal-regulated kinase 1/2 protein levels. These results suggest that doxorubicin synergizes with cucurbitacin B in induction of cytotoxicity in anaplastic thyroid carcinoma cells. Moreover, synergistic cytotoxicity of doxorubicin with cucurbitacin B is mediated by B-cell chronic lymphocytic leukemia/lymphoma 2 family proteins, survivin, and reactive oxygen species and modulated by Janus kinase 2/signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 in anaplastic thyroid carcinoma cells.

Lee H, Lee H, Cho YK
Cytokeratin7 and cytokeratin19 expression in high grade cervical intraepithelial neoplasm and squamous cell carcinoma and their possible association in cervical carcinogenesis.
Diagn Pathol. 2017; 12(1):18 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: High risk human papillomavirus (HR HPV) infects cells at the squamocolumnar junction (SCJ) of the cervix, causing cancer. Cytokeratin (CK)7 is an SCJ marker, and stains cervical neoplasia. CK19 is a binding partner of CK7 and expressed in cervical cancer. Despite this possible association between CK7/CK19 and cervical cancer, not much is known about the mechanism of CK7/CK19 involvement in HR HPV-mediated cervical carcinogenesis.
METHODS: We analyzed the expression pattern of CK7, CK19, and p16 by using immunohistochemistry and HPV infection by in situ hybridization in 25 cases of high grade cervical intraepithelial neoplasia (CIN3) and in 30 cases of squamous cell carcinoma (SCC).
RESULTS: CK19, p16, and HPV expression was positive in all CIN3 and SCC cases. CK7 expression was positive in all CIN3 cases and in 20/30 (66%) SCCs. Each protein showed diffuse or patchy staining with topographic distinction. Patchy staining of CK7 and episomal HPV DNA overlapped in the upper layer of CIN3 and central portion of an invasive nest in the SCC, whereas patchy CK19 staining and integrated HPV DNA were usually noted in the lower layer of CIN3 and the periphery of the SCC nest. The p16 staining pattern coincided with that of CK19 in a subset of SCC.
CONCLUSION: These results suggest that CK7 may be more related with viral episomal replication and CK19 with viral integration, contributing to viral replication and malignant transformation in HR HPV infected cells. In addition, coordinate CK7/CK19 staining may be used as a valuable marker for predicting physical status of HR HPV and E7 oncoprotein level in cervical tumor.

Jeong YJ, Jung JW, Cho YY, et al.
Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT.
Nucl Med Rev Cent East Eur. 2017; 20(1):32-38 [PubMed] Related Publications
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed.
MATERIAL AND METHODS: Two-hundred seven female patients with IDC who underwent pretreatment fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) were enrolled. The pSUVmax was compared with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), axillary lymph node (LN) metastasis, stage and HIF-1a expression. The prognostic value of pSUVmax for PFS was assessed using the Kaplan-Meier method.
RESULTS: pSUVmax was significantly higher in patients with HIF-1a expression ≥ 2 compared to patients with HIF-1a expression < 2 (5.2 ± 4.5 vs. 3.7 ± 3.1, p = 0.008). pSUVmax was also significantly higher in higher stage (p < 0.000001), ER-negative tumors (p < 0.0001), PR-negative tumors (p = 0.0011) and positive LN metastasis (p = 0.0013). pSUVmax was significantly higher in patients with progression compared to patients who were disease-free (6.8 ± 4.4 vs. 4.1 ± 3.7, p = 0.0005). A receiver-operating characteristic curve demonstrated a pSUVmax of 6.51 to be the optimal cutoff for predicting PFS (sensitivity: 53.6%, specificity: 86.0%). Patients with high pSUVmax (> 6.5) had significantly shorter PFS compared to patients with low pSUVmax (p < 0.0001).
CONCLUSIONS: pSUVmax on pretreatment F-18 FDG PET/ CT reflect expression of HIF-1a and can be used as a good surrogate marker for the prediction of progression in patients with IDC. The amount of FDG uptake is determined by the presence of glucose metabolism and hypoxia in breast cancer cell.

Seo AN, Yoon G, Ro JY
Clinicopathologic and Molecular Pathology of Collecting Duct Carcinoma and Related Renal Cell Carcinomas.
Adv Anat Pathol. 2017; 24(2):65-77 [PubMed] Related Publications
Collecting duct carcinoma (CDC) and related tumors [ie, renal medullary carcinoma (RMC)] are rare types of highly aggressive renal cell carcinomas (RCC) with poor prognosis. Because of the rarity and diagnostic uncertainty of them, their molecular pathology and significance have not yet been fully elucidated. CDC, RMC, fumarate hydratase-deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC HLRCC-RCC), and recently reported anaplastic lymphoma kinase (ALK)-rearrangement RCC have significant morphologic overlaps, but they are separately distinct entities having different molecular pathway and clinical settings. CDC is more likely to occur in middle to old age population with immunoreactivity for PAX8 and integrase interactor-1 proteins (INI-1). Various chromosomal and genomic alterations have been reported with inconsistent results. In contrast, RMC is more likely to occur in younger patients with sickle cell trait. In RMC, loss of INI-1 expression and OCT3/4 expression are distinguished compared with other RCCs. Finally, ALK-rearrangement RCC seems to have 2 different clinical settings, one with sickle cell trait (VCL-ALK fusion) and the other without (other fusions such as TPM3-ALK, EML4-ALK, and STRN-ALK fusions). Interestingly, VCL-ALK fusion was found in pediatric patients with sickle cell trait, whereas other fusions were detected in adolescent or adult without sickle cell trait. Taken together, CDC and related tumors such as RMC, fumarate hydratase-deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC), and ALK-rearrangement RCC are the distinct entities and their recognition is important for the development of future personalized therapeutic options. This review updates the clinicopathologic features of these tumors with overlapping morphology and outcome.

Ryu SH, Heo SH, Park EY, et al.
Selumetinib Inhibits Melanoma Metastasis to Mouse Liver via Suppression of EMT-targeted Genes.
Anticancer Res. 2017; 37(2):607-614 [PubMed] Related Publications
AIM: We investigated the therapeutic effects of a mitogen-activated protein (MEK) inhibitor, selumetinib, in a hepatic melanoma metastasis model and studied its possible mechanism of action.
MATERIALS AND METHODS: Melanoma cell lines were exposed to selumetinib under different experimental conditions. We established a mouse model of liver metastasis and treated mice orally with vehicle or selumetinib and then evaluated metastasis progress.
RESULTS: Growth inhibition was observed in melanoma cells as a consequence of G1-phase cell-cycle arrest and the subsequent induction of apoptosis in a dose- and time-dependent manner. Mice with established liver metastases that were treated with selumetinib exhibited significantly less tumor progression than vehicle-treated mice. c-Myc expression in metastasized liver tissues were suppressed by selumetinib. Moreover, oral treatment with selumetinib modulated expression of epithelial-to-mesenchymal transition- and metastasis-related genes, including integrin alpha-5 (ITGA5), jagged 1 (JAG1), zinc finger E-box-binding homeobox 1 (ZEB1), NOTCH, and serpin peptidase inhibitor clade E (SERPINE1).
CONCLUSION: We established a mouse model of hepatic metastasis using a human melanoma cell line, such models are essential in elucidating the therapeutic effects of anti-metastatic drugs. Our data suggest the possibility that selumetinib presents a new strategy to treat liver metastasis in patients with melanoma by suppressing epithelial-to-mesenchymal transition-related genes.

Lim YS, Cha W, Park MW, et al.
HIF1α in Tumorigenesis of Adenoid Cystic Carcinoma.
Anticancer Res. 2017; 37(2):599-606 [PubMed] Related Publications
BACKGROUND: Tumor hypoxia induces hypoxia-inducible factor-1α (HIF1α), which can influence tumorigenesis and metastasis. We evaluated the expression of HIF1α and the effect of HIF1α inhibitors in adenoid cystic carcinoma (ACC).
MATERIALS AND METHODS: HIF1α expression was demonstrated in ACC cell lines (ACC2 and ACCM). The effect of HIF1α inhibitors was evaluated. A systemic metastasis model was developed. The number of metastatic pulmonary nodules were analyzed.
RESULTS: The ACCM cell line demonstrated greater HIF1α expression and invasion than ACC2. The expression of HIF1α and invasion of ACC cells were blocked by HIF1α siRNA. HIF1α inhibitors 17-N-allylamino-17-demethoxygeldanamycin (17AAG) and echinomycin inhibited cell invasion. 17AAG inhibited metastasis in the animal model, although not statistically significantly.
CONCLUSION: HIF1α siRNA and 17AAG and echinomycin blocked invasion by ACC2 and ACCM cells. 17AAG exhibited therapeutic potential for inhibition of metastasis. Our results provide positive evidence that HIF1α is a promising research pathway for therapy of ACC.

Kang E, Kim YM, Kim DH, et al.
Life-threatening bleeding from gastric mucosal angiokeratomas during anticoagulation: A case report of Fabry disease.
Medicine (Baltimore). 2017; 96(6):e6063 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Angiokeratomas are the earliest manifestation of Fabry disease (FD), and the extent of their appearance is related to disease severity. Angiokeratomas are mostly found on cutaneous regions.
PATIENT CONCERNS, DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Here we report an FD patient with widespread gastrointestinal angiokeratomas who developed life-threatening bleeding following anticoagulation for atrial fibrillation.
LESSONS: Careful observation for gastrointestinal bleeding is warranted for patients on anticoagulation with extensive cutaneous angiokeratomas. Furthermore, our experience suggests that surveillance is needed to assess the prevalence and extent of gastrointestinal angiokeratomas in patients with FD.

Kim J, Baek SJ, Kang DW, et al.
Robotic Resection is a Good Prognostic Factor in Rectal Cancer Compared with Laparoscopic Resection: Long-term Survival Analysis Using Propensity Score Matching.
Dis Colon Rectum. 2017; 60(3):266-273 [PubMed] Related Publications
BACKGROUND: Robotic total mesorectal excision for rectal cancer has rapidly increased and has shown short-term outcomes comparable to conventional laparoscopic total mesorectal excision. However, data for long-term oncologic outcomes are limited.
OBJECTIVE: The aim of this study is to evaluate long-term oncologic outcomes of robotic total mesorectal excision compared with laparoscopic total mesorectal excision.
DESIGN: This was a retrospective study.
SETTINGS: This study was conducted in a tertiary referral hospital.
PATIENTS: A total of 732 patients who underwent totally robotic (n = 272) and laparoscopic (n = 460) total mesorectal excision for rectal cancer were included in this study.
MAIN OUTCOME MEASURES: We compared clinicopathologic outcomes of patients. In addition, short- and long-term outcomes and prognostic factors for survival were evaluated in the matched robotic and laparoscopic total mesorectal excision groups (224 matched pairs by propensity score).
RESULTS: Before case matching, patients in the robotic group were younger, more likely to have undergone preoperative chemoradiation, and had a lower tumor location than those in the laparoscopic group. After case matching most clinicopathologic outcomes were similar between the groups, but operative time was longer and postoperative ileus was more frequent in the robotic group. In the matched patients excluding stage IV, the overall survival, cancer-specific survival, and disease-free survival were better in the robotic group, but did not reach statistical significance. The 5-year survival rates for robotic and laparoscopic total mesorectal excision were 90.5% and 78.0% for overall survival, 90.5% and 79.5% for cancer-specific survival, and 72.6% and 68.0% for disease-free survival. In multivariate analysis, robotic surgery was a significant prognostic factor for overall survival and cancer-specific survival (p = 0.0040, HR = 0.333; p = 0.0161, HR = 0.367).
LIMITATIONS: This study has the potential for selection bias and limited generalizability.
CONCLUSIONS: Robotic total mesorectal excision for rectal cancer showed long-term survival comparable to laparoscopic total mesorectal excision in this study. Robotic surgery was a good prognostic factor for overall survival and cancer-specific survival, suggesting potential oncologic benefits.

Moon SM, Lee SM, Kang H, Choi HJ
Presternal subcutaneous bronchogenic cyst in adolescence: A case report and unusual ultrasonographic findings.
Medicine (Baltimore). 2017; 96(5):e6054 [PubMed] Free Access to Full Article Related Publications
Subcutaneous bronchogenic cysts have been described rarely, particularly among adolescents. Only a few reports have described the ultrasonographic features of bronchogenic cysts, characterizing them as nonspecific cystic masses with or without internal echogenic foci or debris. Therefore, it is hard to differentiate subcutaneous bronchogenic cysts from other subcutaneous cystic tumors ultrasonographically.We report a case of presternal subcutaneous bronchogenic cyst in an 18-year-old man with unusual ultrasonographic findings. Ultrasonography revealed a small, oval, cystic mass containing a well-circumscribed, heterogeneously hypoechoic, egg-shaped lesion in the dependent portion of the mass within the subcutaneous fat layer overlying the sternum.Surgical excision was performed, and the cystic mass was diagnosed as a bronchogenic cyst. On pathological examination, the internal, heterogeneously hypoechoic, ball-like lesion was found to be mucous material within the cyst. To our knowledge, this is the first reported case of a presternal subcutaneous bronchogenic cyst presenting with a ball-like lesion inside of the cyst. This unusual ultrasonographic feature can be a clue to the diagnosis of subcutaneous bronchogenic cyst.In conclusion, if an anechoic cyst containing an internal, well-circumscribed, hypoechoic ball-like lesion is seen in the presternal subcutaneous fat layer, subcutaneous bronchogenic cyst should be considered in the differential diagnosis of subcutaneous cystic masses.

Kim J, Cho SG, Kang SR, et al.
Preparation for radioactive iodine therapy is not a risk factor for the development of hyponatremia in thyroid cancer patients.
Medicine (Baltimore). 2017; 96(5):e6004 [PubMed] Free Access to Full Article Related Publications
The aim of this study was to evaluate whether the preparation for radioactive iodine (RAI) therapy by thyroid hormone withdrawal (THW) or a low-iodine diet (LID) can be risk factors for the development of hyponatremia in patients with differentiated thyroid cancer after thyroidectomy.We retrospectively reviewed the medical records and laboratory findings of 326 patients who underwent preparation for RAI therapy after thyroidectomy from 2012 to 2014. Demographic and clinical variables including the method of thyrotropin stimulation and duration of LID were assessed. Serum sodium was measured twice, before operation and before RAI therapy.Hyponatremia was detected in only 3 patients (0.9%) before operation, but in 15 patients (4.6%) before RAI therapy. None of the patients had severe hyponatremia after preparation for RAI therapy. Pre-RAI therapy serum sodium was correlated with the method of thyrotropin stimulation (TWH vs recombinant human thyroid stimulating hormone, P = 0.014) and duration of LID (r = -0.131, P = 0.018); however, the preparation of RAI therapy, THW and LID, did not affect the development of hyponatremia in logistic regression analysis. Preoperative serum sodium was a significant risk factor for hyponatremia during preparation for RAI therapy.Preparation for RAI therapy by THW or LID is not a risk factor for the development of hyponatremia in patients with thyroid cancer. The development of hyponatremia was neither frequent nor severe during preparation for RAI therapy. Physicians should not be greatly concerned about rare life-threatening hyponatremia during preparation for RAI therapy.

Jeong E, Hyun SH, Moon SH, et al.
Relation between tumor FDG uptake and hematologic prognostic indicators in stage I lung cancer patients following curative resection.
Medicine (Baltimore). 2017; 96(5):e5935 [PubMed] Free Access to Full Article Related Publications
Hematologic parameters of systemic inflammation are receiving attention as promising prognostic indicators in cancer patients. Here, we investigated the relation and compared the prognostic values of circulating blood cell-based parameters and tumor F-fluoro-2-deoxyglucose (FDG) uptake in patients with stage I nonsmall cell lung cancers (NSCLC).Subjects were 1034 patients with newly diagnosed stage I NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) followed by curative resection. Total white blood cell (WBC) count, absolute neutrophil, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were obtained. Tumor FDG uptake was measured as SUVmax.WBC, neutrophil and lymphocyte counts, and NLR demonstrated weak but significant correlation to tumor SUVmax. Using the upper quartile as cutoff, patients with high tumor SUVmax had significantly higher WBC, neutrophil and lymphocyte counts, and greater NLR. There were 144 recurrences (13.9%) over a median follow-up of 29.5 months. On Cox proportional hazards regression analysis, WBC count, tumor SUVmax, age, gender, smoking, cell type, and tumor stage were significant univariate prognostic factors. On multivariate analysis, high tumor SUVmax (HR = 2.22; 95% CI, 1.52-3.25; P < 0.001), tumor stage 1B (HR = 2.11; 95% CI, 1.47-3.01; P < 0.001), and old age (HR = 1.03; 95% CI, 1.01-1.05; P = 0.002) were significant independent predictors of poor survival. Finally, high tumor SUVmax remained a significant predictor of prognosis in both low and WBC count groups.Circulating blood counts showed significant correlation to tumor FDG uptake in early stage NSCLC. WBC count was a significant univariate variable, but tumor FDG uptake was a superior and independent predictor of outcome. Hence, tumor FDG uptake effectively stratified prognosis in patients with low as well as high WBC count.

Kim HW, Lee JC, Paik KH, et al.
Serum interleukin-6 is associated with pancreatic ductal adenocarcinoma progression pattern.
Medicine (Baltimore). 2017; 96(5):e5926 [PubMed] Free Access to Full Article Related Publications
Several reports showed that interleukin-6 (IL-6) or -8 (IL-8) might be useful inflammatory biomarkers for pancreatic ductal adenocarcinoma (PDAC), although these clinical impact is still open to debate. The aim of this study was to elucidate whether serum levels of IL-6 and IL-8 at diagnosis could predict the tumor progression pattern of PDAC, especially in extensive hepatic metastasis.According to the tumor burden of hepatic metastasis at the last follow-up, tumor progression pattern was defined as follows: no or limited (unilobar involvement and 5 or less in the within liver, limited group) and extensive hepatic metastasis (bilobar or more than 5, progressed group). Fifty-three PDAC patients with initially no or limited hepatic metastasis were enrolled retrospectively.Around 42 (79.2%) were included in the limited and 11 (20.8%) in the progressed group. The median serum level of IL-6 in the progressed group was elevated significantly compared with the limited group. However, the median serum level of IL-8 was not. Furthermore, multivariate analysis revealed that the elevated serum level of IL-6 was an independent risk factor for progression to extensive hepatic metastasis (odds ratio 1.928, 95% confidence interval 1.131-3.365, P = 0.019), but IL-8 was not. However, higher IL-6 did not predict shorter survival.High serum IL-6 can be an independent risk factor for progression to extensive hepatic metastasis in PDAC patients.

Lee HW, Park TI, Jang SY, et al.
Clinicopathological characteristics of TERT promoter mutation and telomere length in hepatocellular carcinoma.
Medicine (Baltimore). 2017; 96(5):e5766 [PubMed] Free Access to Full Article Related Publications
Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046-2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

Jung DH, Hwang S, Song GW, et al.
Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection.
Ann Transplant. 2017; 22:42-52 [PubMed] Related Publications
BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory.

Lee SH, Park MJ, Choi SI, et al.
Reactive oxygen species modulator 1 (Romo1) as a novel diagnostic marker for lung cancer-related malignant effusion.
Medicine (Baltimore). 2017; 96(4):e5975 [PubMed] Free Access to Full Article Related Publications
Reactive oxygen species modulator 1 (Romo1) is a novel protein that plays an important role in intracellular reactive oxygen species generation. Recently, Romo1 has been suggested to have diagnostic and prognostic potential in lung cancer. However, there is no data on the diagnostic value of Romo1 level in malignant pleural effusion. We evaluated the clinical usefulness of Romo1 in pleural fluid for the diagnosis of malignant effusion in lung cancer patients. Pleural fluid Romo1 level was measured using enzyme-linked immunosorbent assay and compared between lung cancer-associated malignant effusion (n = 53; 29 adenocarcinomas and 24 squamous cell carcinomas) and benign pleural effusions (n = 91; 31 tuberculous pleurisy, 30 parapneumonic effusion, and 30 transudate). The discriminative power of Romo1 for lung cancer-associated malignant effusion was determined using receiver operating characteristic (ROC) curve analysis and compared with those of other tumor markers. Median Romo1 level in lung cancer-associated malignant effusion was 99.3 ng/mL, which was significantly higher than that in benign pleural effusions (P < 0.001). The optimal cutoff value of Romo1 to discriminate lung cancer-associated malignant effusion from benign effusions was 67.0 ng/mL with a sensitivity of 73.8% and a specificity of 84.1%. The area under the curve was 0.837 (95% confidence interval [CI]: 0.750-0.886), which was significantly better than that of cytokeratin 19 fragments (P < 0.001). Pleural fluid Romo1 could discriminate lung cancer from benign diseases with considerable sensitivity and specificity. Our findings suggest a diagnostic potential of Romo1 for lung cancer-associated malignant effusion.

Moon JY, Baek SW, Ryu H, et al.
VIP (etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma.
Medicine (Baltimore). 2017; 96(4):e5942 [PubMed] Free Access to Full Article Related Publications
We retrospectively reviewed outcomes of treatment with VIP (combination of etoposide, ifosfamide, and cisplatin) in patients with previously treated soft tissue sarcoma (STS).We analyzed the medical records of patients with advanced or relapsed STS who had undergone VIP treatment as second-line or more chemotherapy between January 2000 and December 2015. The patients were treated with a combination of etoposide (100 mg/m for 5 days), ifosfamide (2000 mg/m for 2 days), and cisplatin (20 mg/m for 5 days) once every 4 weeks. Treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed in all patients and between responder and nonresponder groups (responders showed a tumor response to any prior systemic chemotherapy before VIP).Twenty-four patients with a median age of 50 years (range: 20-68 years) were treated with VIP. Eleven (45.8%) patients were male and 7 (29.2%) received 2 or more chemotherapy regimens before VIP. Median PFS was 3.7 months (95% confidence interval [CI], 1.3-6.1 months) and median OS was 10.0 months (95% CI, 6.6-13.5). The overall response rate was 37.5%, and the disease control rate was 50%. The responder group showed better PFS (7.7 months vs 3.0 months; P = 0.101) and significantly improved OS (11.0 months vs 8.8 months; P = 0.039) compared to those of nonresponders. All patients reported some grade of hematological toxicity. The most frequently encountered hematological toxicity was neutropenia (any grade, 77.7%; grade 3 or 4, 74.0%).VIP might be effective in patients with previously treated STS.

Kim WJ, Kim KH, Shin MH, et al.
Totally laparoscopic anatomical liver resection for centrally located tumors: A single center experience.
Medicine (Baltimore). 2017; 96(4):e5560 [PubMed] Free Access to Full Article Related Publications
Laparoscopic major hepatectomy is a common procedure that has been reported frequently; however, laparoscopic resection of centrally located tumors involving segments 4, 5, and 8 remains a technically difficult procedure because it requires 2 transection planes and dissection of numerous branches of the hepatic vein and glissonean capsule compared to hemi-hepatectomy. Here, we present 7 cases of totally laparoscopic right anterior sectionectomy (Lap-RAS) and 3 cases of totally laparoscopic central bisectionectomy (Lap-CBS).Between May 2013 and January 2015, 10 totally laparoscopic anatomical resections of centrally located tumors were performed in our institution. The median age of the patients was 54.2 (38-72) years and the median ICG-R15 was 10.4 (3.9-17.4). There were 8 patients with hepatocellular carcinoma (HCC) and 2 with metastatic colorectal cancer. All the HCC patients has the liver function impairment on the degree of Child-Pugh score A.The mean operation time was 330 ± 92.7 minutes with an estimated blood loss of 325 ± 234.5 mL. Only 1 patient required transfusion during surgery. Mean postoperative hospital stay was 9.5 ± 3.4 day and postop complication was reported only 1 case that has the fluid collection at the resection margin of the liver. Mean resection margin was 8.5 ± 6.1 mm and tumor size was 2.9 ± 1.9 cm.Totally lap-RAS and lap-CBS are feasible operative procedures in patients with centrally located tumor of the liver and particularly in patients with limited liver function such as those with cirrhosis.

Lee JK, Rho YJ, Jeong DM, et al.
Diagnostic Clue of Meningeal Melanocytoma: Case Report and Review of Literature.
Yonsei Med J. 2017; 58(2):467-470 [PubMed] Free Access to Full Article Related Publications
In this report, the patient was pre-diagnosed as meningioma before surgery, which turned out to be meningeal melanocytoma. Hence, we will discuss the interpretation of imaging and neurological statuses that may help avoid this problem. A 45-year-old man had increasing pain around the neck 14 months prior to admission. His cervical spine MR imaging revealed a space-occupying, contrast-enhancing mass within the dura at the level of C1. The neurologic examination revealed that the patient had left-sided lower extremity weakness of 4+, decreased sensation on the right side, and hyperreflexia in both legs. Department of Neuroradiology interpreted CT and MR imaging as meningiom. The patient underwent decompression and removal of the mass. We confirmed diagnosis as meningeal melanocytoma through pathologic findings. Afterwards, we reviewed the patient's imaging work-up, which showed typical findings of meningeal melanocytoma. However, it was mistaken as meningioma, since the disease is rare.

Kim D, Lim JY, Shim KW, et al.
Sacral Reconstruction with a 3D-Printed Implant after Hemisacrectomy in a Patient with Sacral Osteosarcoma: 1-Year Follow-Up Result.
Yonsei Med J. 2017; 58(2):453-457 [PubMed] Free Access to Full Article Related Publications
Pelvic reconstruction after sacral resection is challenging in terms of anatomical complexity, excessive loadbearing, and wide defects. Nevertheless, the technological development of 3D-printed implants enables us to overcome these difficulties. Here, we present a case of sacral osteosarcoma surgically treated with hemisacrectomy and sacral reconstruction using a 3D-printed implant. The implant was printed as a customized titanium prosthesis from a 3D real-sized reconstruction of a patient's CT images. It consisted mostly of a porous mesh and incorporated a dense strut. After 3-months of neoadjuvant chemotherapy, the patient underwent hemisacretomy with preservation of contralateral sacral nerves. The implant was anatomically installed on the defect and fixed with a screw-rod system up to the level of L3. Postoperative pain was significantly low and the patient recovered sufficiently to walk as early as 2 weeks postoperatively. The patient showed left-side foot drop only, without loss of sphincter function. In 1-year follow-up CT, excellent bony fusion was noticed. To our knowledge, this is the first report of a case of hemisacral reconstruction using a custom-made 3D-printed implant. We believe that this technique can be applied to spinal reconstructions after a partial or complete spondylectomy in a wide variety of spinal diseases.

Han JH, Yoon YE, Kim SY, et al.
Preoperative Lymphocyte-Monocyte Ratio Ameliorates the Accuracy of Differential Diagnosis in Non-Metastatic Infiltrative Renal Masses.
Yonsei Med J. 2017; 58(2):388-394 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Distinguishing infiltrative renal cell carcinoma (RCC) from transitional cell carcinoma (TCC) is a challenging issue due to their radiologic similarities. We evaluated systemic inflammatory biomarkers as parameters for distinguishing tumor types.
MATERIALS AND METHODS: A computerized search of medical records from November 2005 to October 2015 identified 116 patients with infiltrative renal masses who were difficult to diagnose confirmatively in radiological study. We investigated the diagnostic efficacy among these patients with their preoperative absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC), absolute monocyte counts (AMC), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR).
RESULTS: The infiltrative RCC group demonstrated significantly lower ALC {1449/μL (1140-1896), median [interquartile range (IQR)]} than the TCC group [1860/μL (1433-2342), p=0.016]. LMR [median (IQR)] also was lower in the infiltrative RCC group [2.98 (2.32-4.14) vs. TCC group 4.10 (2.86-6.09); p=0.011]. In subgroup analysis, non-metastatic infiltrative RCC showed lower ALC and LMR and higher NLR than non-metastatic TCC. Within non-metastatic infiltrative renal masses, multivariate logistic regression analysis revealed that younger patient age and lower LMR were associated with infiltrative RCC [odds ratios (OR) 0.874, p=0.024 and OR 0.461, p=0.048, respectively]. Receiver operating characteristic curve analysis showed that younger age and lower LMR were highly predictive of non-metastatic RCC (area under the curve=0.919, p<0.001).
CONCLUSION: Age and LMR were significantly different between patients with infiltrative renal mass. These are potential markers for distinguishing between infiltrative RCC and TCC without metastasis.

Kim NH, Suh JY, Park JH, et al.
Parameters of Glucose and Lipid Metabolism Affect the Occurrence of Colorectal Adenomas Detected by Surveillance Colonoscopies.
Yonsei Med J. 2017; 58(2):347-354 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Limited data are available regarding the associations between parameters of glucose and lipid metabolism and the occurrence of metachronous adenomas. We investigated whether these parameters affect the occurrence of adenomas detected on surveillance colonoscopy.
MATERIALS AND METHODS: This longitudinal study was performed on 5289 subjects who underwent follow-up colonoscopy between 2012 and 2013 among 62171 asymptomatic subjects who underwent an initial colonoscopy for a health check-up between 2010 and 2011. The risk of adenoma occurrence was assessed using Cox proportional hazards modeling.
RESULTS: The mean interval between the initial and follow-up colonoscopy was 2.2±0.6 years. The occurrence of adenomas detected by the follow-up colonoscopy increased linearly with the increasing quartiles of fasting glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglycerides measured at the initial colonoscopy. These associations persisted after adjusting for confounding factors. The adjusted hazard ratios for adenoma occurrence comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, and triglycerides were 1.50 [95% confidence interval (CI), 1.26-1.77; p(trend)<0.001], 1.22 (95% CI, 1.04-1.43; p(trend)=0.024), 1.22 (95% CI, 1.02-1.46; p(trend)=0.046), 1.36 (95% CI, 1.14-1.63; p(trend)=0.004), and 1.19 (95% CI, 0.99-1.42; p(trend)=0.041), respectively. In addition, increasing quartiles of low-density lipoprotein-cholesterol and apolipoprotein B were associated with an increasing occurrence of adenomas.
CONCLUSION: The levels of parameters of glucose and lipid metabolism were significantly associated with the occurrence of adenomas detected on surveillance colonoscopy. Improving the parameters of glucose and lipid metabolism through lifestyle changes or medications may be helpful in preventing metachronous adenomas.

Sun JM, Lee SH, Ahn JS, et al.
Osimertinib for the treatment of non-small cell lung cancer.
Expert Opin Pharmacother. 2017; 18(2):225-231 [PubMed] Related Publications
INTRODUCTION: The T790 M mutation of the epidermal growth factor receptor (EGFR) gene is the most common mechanism underlying resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Osimertinib, a third-generation EGFR TKI, shows robust clinical efficacy in patients with T790 M-mutated lung cancer. Areas covered: We analyzed and reviewed clinical data for which patients who experienced acquired resistance to first- or second-generation EGFR TKIs. In addition, we briefly reviewed the potential role of osimertinib as a first-line therapy. Expert opinion: Osimertinib was recently licensed for use in NSCLC patients with acquired resistance to other EGFR TKIs due to a T790 M mutation. However, unresolved issues surrounding the optimal application of osimertinib remain, specifically the development of a plasma-based mutation test to overcome the difficulty of repeat biopsy, the efficacy of osimertinib for brain or leptomeningeal metastases, the development of resistance to osimertinib, and the use of osimertinib therapy as a first-line treatment. Many ongoing studies are currently exploring these issues.

Kumar Mongre R, Sharma N, Singh Sodhi S, et al.
Novel phyto-derivative BRM270 inhibits hepatocellular carcinoma cells proliferation by inducing G2/M phase cell cycle arrest and apoptosis in xenograft mice model.
Biomed Pharmacother. 2017; 87:741-754 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is a major threat to human health worldwide and development of novel antineoplastic drug is demanding task. BRM270 is a proprietary combination of traditional medicinal herbs, has been shown to be effective against a wide range of stem-like cancer initiating cells (SLCICs). However, the underlying mechanism and antitumor efficacy of BRM270 in human hepatocellular carcinoma (HCC) cells have not been well elucidated till date. Here we studied the tumoricidal effect of BRM270 on human-CD133(+) expressing stem-like HepG-2 and SNU-398 cells. Gene expression profiling by qPCR and specific cellular protein expressions was measured using immunocytochemistry/western blot analysis. In vivo efficacy of BRM270 has been elucidated in the SLCICs induced xenograft model. In addition, 2DG-(2-Deoxy-d-Glucose) optical-probe guided tumor monitoring was performed to delineate the size and extent of metastasized tumor. Significant (P<0.05) induction of Annexin-V positive cell population and dose-dependent upregulation of caspase-3 confirmed apoptotic cell death by pre/late apoptosis. In addition, bright field and fluorescence microscopy of treated cells revealed apoptotic morphology and DNA fragmentation in Hoechst33342 staining. Levels of c-Myc, Bcl-2 and c-Jun as invasive potential apoptotic marker were detected using qPCR/Western blot. Moreover, BRM270 significantly (P<0.05) increased survival rate that observed by Kaplan-Meier log rank test. In conclusion, these results indicate that BRM270 can effectively inhibit proliferation and induce apoptosis in hepatoma cells by down-regulating CyclinD1/Bcl2 mediated c-Jun apoptotic pathway.

Lee SJ, Kim JH, Park SJ, et al.
Optimal glycemic target level for colon cancer patients with diabetes.
Diabetes Res Clin Pract. 2017; 124:66-71 [PubMed] Related Publications
AIMS: The aim of this study was to evaluate the differences in mortality among colon cancer patients with or without diabetes and to determine optimal glycemic target level for colon cancer patients with diabetes.
METHODS: A total of 741 patients with colon cancer between April 1999 and December 2010 were reviewed. The non-diabetes group had a fasting plasma glucose <126mg/dL, and the diabetes group had a fasting plasma glucose ⩾126mg/dL. Patients with diabetes were further divided based on glycemic control into either the uncontrolled subgroup (HbA1c ⩾8%) or the well-controlled subgroup (HbA1c <8%).
RESULTS: Patients with diabetes had significantly shorter overall survival and median survival than non-diabetes patients. Uncontrolled diabetes patients had significantly shorter overall survival and median survival than well-controlled diabetes patients. The relative risk of mortality for diabetes patients was higher than non-diabetes patients (relative risk 1.17). The relative risk of mortality in uncontrolled diabetes patients was significantly higher than in well-controlled diabetes patients (relative risk 4.58). The area under the curve for mortality and HbA1c level was 0.73. The cut off HbA1c level was 7.75%.
CONCLUSIONS: A optimal glycemic control level for colon cancer patients with diabetes should be recommended as an HbA1c of 7.8% or below.

Kim KM, Kim CY, Hong SM, Jang KY
A primary pure pancreatic-type acinar cell carcinoma of the stomach: a case report.
Diagn Pathol. 2017; 12(1):10 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Acinar cell carcinoma represents only 1-2% of exocrine pancreatic neoplasms. On exceptionally rare occasions, primary acinar cell carcinoma can occur in ectopic locations. Herein, we report a case of pure pancreatic-type acinar cell carcinoma arising in the stomach.
CASE PRESENTATION: A 54-year-old male presented with a gastric submucosal mass detected by endoscopic examination. Laparoscopic wedge resection was performed. Macroscopically, the 2.7 cm yellowish mass was located in the submucosa of the stomach. Microscopically, the tumor was well circumscribed and had a homogeneous acinar architecture. The tumor cells were small and had a minimal amount of cytoplasm. The nuclei of the tumor cells were round to oval with finely dispersed chromatin. The tumor cells were strongly positive for α1-antitrypsin, chymotrypsin, and α1-antichymotrypsin immunostaining, consistent with pancreatic exocrine differentiation. There was no clinical or radiologic evidence of primary pancreatic or head and neck tumors. After surgical resection of the tumor, there was no recurrence or metastasis during 33 months follow-up.
CONCLUSION: In this report, we have presented a rare case of primary pure pancreatic-type acinar cell carcinoma arising in the stomach and suggest that it could be helpful if the pathologist were aware that pancreatic-type acinar cell carcinoma could arise in the stomach as a polypoid submucosal tumor in the routine diagnostic field of gastric endoscopy.

Oyunchimeg B, Hwang JH, Ahmed M, et al.
Complementary and alternative medicine use among patients with cancer in Mongolia: a National hospital survey.
BMC Complement Altern Med. 2017; 17(1):58 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Complementary and alternative medicine (CAM) use is popular in former Soviet Central Asian countries including Mongolia. However, no studies are available on CAM use among patients with cancer in countries of this region. The aim of this research is to describe the prevalence and patterns of CAM use by patients with cancer in Mongolia.
METHODS: A cross-sectional study was conducted using data from 482 cancer patients attending the National Cancer Center in Mongolia from September 2015 to February 2016. The survey instrument included 25 questions regarding CAM used, factors associated with use of CAM, cancer-related characteristics, and participants' socio-demographic profile.
RESULTS: Among 482 respondents (response rate, 95.6%), 47.9% reported using one or more CAM modalities. Products of animal origin were the most popular modalities of CAM, followed by herbal products. Half of the users used CAM while receiving conventional treatment of cancer. Among users, only 29% discussed the CAM use with their doctors. Female gender, younger age, higher education, shorter disease duration, and prior use of CAM were significantly associated with CAM use.
CONCLUSIONS: CAM appears to be widely accepted by patients with cancer in Mongolia. The findings support the urgent need for further in-depth study into commonly used oral CAM products and their potential effects on health of patients with cancer in Mongolia. High prevalence of CAM use among cancer patients in our study warrants further studies in other countries of Central Asia.

Chen TH, Yen AM, Fann JC, et al.
Clarifying the debate on population-based screening for breast cancer with mammography: A systematic review of randomized controlled trials on mammography with Bayesian meta-analysis and causal model.
Medicine (Baltimore). 2017; 96(3):e5684 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality.
METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.
RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.
CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

Kim GJ, Lee JH, Lee DH
Clinical and prognostic significance of Merkel cell polyomavirus in nonsmall cell lung cancer.
Medicine (Baltimore). 2017; 96(3):e5413 [PubMed] Free Access to Full Article Related Publications
Recently, an association between Merkel cell polyomavirus (MCPyV) and epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) was reported. However, the underlying carcinogenic effects and the prognosis related to MCPyV are still unclear. The aim of this study was to clarify the incidence and prognosis related to MCPyV infections in NSCLC.Tissue samples from 167 NSCLC patients (92 with squamous cell carcinomas [SCCs] and 75 with adenocarcinomas) were analyzed for the presence of MCPyV and EGFR mutations. Clinicopathological characteristics, disease-free survival rate, and overall survival rate were assessed with respect to MCPyV.MCPyV DNA was detected in 30 patients (18.0%) out of 167 patients, and EGFR mutations were found in 31 out of 127 patients (24.4%). EGFR mutations were more frequently detected in MCPyV-positive patients than in MCPyV-negative patients; however, this did not reach statistical significance (P = 0.075). There was no difference in overall survival between patients with and without MCPyV infections. The disease-free survival rate of patients with pN0 stage, SCC, or EGFR mutations was lower for patients with MCPyV than without MCPyV (P = 0.036, 0.042, and 0.050, respectively).Although the prevalence of MCPyV infection was relatively low, the presence of MCPyV DNA was significantly correlated with cancer prognosis in subgroups of NSCLC patients. These results suggest that MCPyV may be partly associated with pathogenesis and prognosis in some cases of NSCLC.

Kim TS, Lim MS, Hong YJ, et al.
Significance of "Not Detected but Amplified" Results by Real-Time PCR Method for HPV DNA Detection.
Biomed Res Int. 2016; 2016:5170419 [PubMed] Free Access to Full Article Related Publications
Human papillomavirus (HPV) infection is an important etiologic factor in cervical carcinogenesis. Various HPV DNA detection methods have been evaluated for clinicopathological level. For the specimens with normal cytological finding, discrepancies among the detection methods were frequently found and adequate interpretation can be difficult. 6,322 clinical specimens were submitted and evaluated for real-time PCR and Hybrid Capture 2 (HC2). 573 positive or "Not Detected but Amplified" (NDBA) specimens by real-time PCR were additionally tested using genetic analyzer. For the reliability of real-time PCR, 325 retests were performed. Optimal cut-off cycle threshold (CT ) value was evaluated also. 78.7% of submitted specimens showed normal or nonspecific cytological finding. The distributions of HPV types by real-time PCR were not different between positive and NDBA cases. For positive cases by fragment analysis, concordance rates with real-time PCR and HC2 were 94.2% and 84.2%. In NDBA cases, fragment analysis and real-time PCR showed identical results in 77.0% and HC2 revealed 27.6% of concordance with fragment analysis. Optimal cut-off CT value was different for HPV types. NDBA results in real-time PCR should be regarded as equivocal, not negative. The adjustment of cut-off CT value for HPV types will be helpful for the appropriate result interpretation.

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