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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

Yang HB, Kim HY, Jung SE, et al.
Pediatric minimally invasive surgery for malignant abdominal tumor: Single center experience.
Medicine (Baltimore). 2019; 98(33):e16776 [PubMed] Related Publications
This study examined the safety and usefulness of minimally invasive surgery (MIS) for malignant abdominal tumors in pediatric patients and analyzed the factors affecting the resection margin, operative time, and hospital stay of neuroblastoma (NBL) patients.We retrospectively reviewed data of pediatric patients who underwent MIS for malignant abdominal tumors from January 2011 to June 2017 at the Seoul National University Children's Hospital. Sex; age at operation; diagnosis; tumor location; operation-related data, such as operation time and transfusion; and follow-up data were reviewed. We divided patients into an excision group and a biopsy group. Detailed pathologic data were reviewed to analyze factors affecting the resection margin of NBL. Median value and range were calculated for all continuous variables. Mann-Whitney test and χ test were used as appropriate. P values of <.05 were considered significant.Thirty-four pediatric patients were included; 21 were boys. The median age was 4 (0.2-18) years. The most common diagnosis was NBL (17 patients; 50.0%). Three patients each were diagnosed with lymphoma, solid pseudopapillary tumor of the pancreas, and teratoma. The median tumor size was 3.4 (0.5-10.2) cm. The median operation time was 108 (55-290) minutes, and the median hospital stay was 5 (2-11) days. The number of conversions to open surgery was 4. There were no postoperative complications or mortality. There were 18 patients in the excision group and 16 in the biopsy group. Diagnosis and the number of patients receiving preoperative chemotherapy differed between the 2 groups. R0 resection of NBL was significantly higher in patients with stage 1 disease and those aged >2 years. There were no clinical factors influencing operative time or hospital stay.MIS was feasible and safe in pediatric patients with malignant abdominal tumors. R0 resection of NBL was related to age and stage.

Pak S, Kim W, Kim Y, et al.
Dihydrotestosterone promotes kidney cancer cell proliferation by activating the STAT5 pathway via androgen and glucocorticoid receptors.
J Cancer Res Clin Oncol. 2019; 145(9):2293-2301 [PubMed] Related Publications
PURPOSE: Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status.
METHODS: Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation.
RESULTS: DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone.
CONCLUSION: DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.

Park YY, An CH, Oh ST, et al.
Expression of CD133 is associated with poor prognosis in stage II colorectal carcinoma.
Medicine (Baltimore). 2019; 98(32):e16709 [PubMed] Related Publications
CD133 is currently believed to be one of the best colorectal cancer stem cell markers. This study aimed to evaluate prognostic significance of CD133 expression in colorectal cancer patients.A total of 303 patients with stage I to III colorectal cancer who underwent curative surgical resection from 2003 to 2008 at a single institution were included. CD133 expression was evaluated using immunohistochemical staining, and clinicopathological data were retrospectively reviewed. The patients were dichotomized after scoring CD133 expression (0 to 2+: low CD133 expression vs 3+ to 4+: high CD133 expression) according to the extent of area of CD133 positive tumor cells (<50% vs ≥50%) and pattern of staining (membranous staining of the luminal surface and/or staining of cellular debris in the tumor glands and cytoplasm).The 5-year overall survival (OS) (61.9% vs 80.2%, P = .001) and disease-free survival (64.8% vs 75.8%, P = .026) were poorer in the high CD133 expression group than the low CD133 expression group. In the multivariate analysis for risk factors of OS in the whole population, higher nodal stage (N2 compared to N0: hazard ratio [HR] 3.141; 95% confidence interval [CI] 1.718-5.744, P < .001), perineural invasion (HR 2.262; 95% CI 1.347-3.798, P = .002) and high CD133 expression (HR 1.929; 95% CI 1.221-3.048, P = .005) were independent poor prognostic factors of OS. Subgroup analyses according to each TNM stage revealed that CD133 expression was associated with OS only within the stage II patients (HR 3.167 95% CI 1.221-8.216, P = .018). Furthermore, the stage II patients demonstrating the high CD133 expression showed survival benefit of adjuvant chemotherapy, regardless of high-risk feature positivity (HR 0.201 95% CI 0.054-0.750, P = .017).High CD133 expression is correlated with poor prognosis in colorectal cancer patients after radical resection. The CD133 expression may serve as a more potent and informative biomarker for prognosis than conventional high-risk features in the stage II colorectal cancer patients.

Kim JY, Lee MY, Lee YC, Shin HY
Neurofibromatosis type 1 with tarsal conjunctiva thickening: A case report.
Medicine (Baltimore). 2019; 98(31):e16699 [PubMed] Related Publications
RATIONALE: We report a rare case of neurofibroma in the form of tarsal conjunctival thickening of the eyelid in patients with neurofibromatosis type 1 (NF1), common ocular complications of which are Lisch nodules, choroidal nodules, and optic nerve glioma.
PATIENT CONCERNS: A 46-year-old female patient was diagnosed with neurofibroma after biopsy and removal of 2 lumbar level intradural masses 15 years ago. She was being monitored without recurrence. When the patient visited our hospital, multiple iris Lisch nodules were found in both her eyes with ill-defined, diffuse thickening in the upper eyelid tarsal conjunctiva of the right eye.
DIAGNOSIS: Neurofibroma was diagnosed by incisional biopsy and immunohistochemistry of the tarsal conjunctiva.
INTERVENTIONS: The patient of the present case did not undergo any additional surgical treatment because tarsal conjunctiva thickening caused little functional problem.
OUTCOMES: The patient has only been regularly examined for changes in size of neurofibroma, and there was no change in size over a 12-month period.
LESSONS: Neurofibroma should be considered as a differential diagnosis if a patient diagnosed with NF1 shows tarsal conjunctiva thickening.

Yoon JK, Byun C, Jo KS, et al.
Clinicopathologic parameters associated with the FDG-avidity in staging of early gastric cancer using 18F-FDG PET.
Medicine (Baltimore). 2019; 98(31):e16690 [PubMed] Related Publications
This study investigated the clinicopathologic factors associated with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) uptake of early gastric cancer (EGC) and used them to design a clinical scoring method to predict FDG-avidity of EGC.Two hundred twenty-nine retrospectively enrolled patients underwent preoperative F-FDG positron emission tomography/computed tomography (PET/CT). Histologic information was obtained by gastrectomy (n = 195) or endoscopic mucosal dissection (n = 34). The association between clinicopathologic factors and F-FDG uptake by the primary tumor was determined. The results were used to develop a clinical scoring method.F-FDG uptake was detected in 49 (17.5%) patients. According to univariate analysis, location, gross type, World Health Organization classification, Lauren classification, size, depth of invasion, and lymphatic invasion were significant variables affecting F-FDG uptake (all P < .05). According to multivariate analysis, location (lower 3rd, P = .035), gross type (0-I, 0-IIa, P < .001), size (≥2.5 cm, P = .026), and depth of invasion (submucosa, P = .007) were significantly associated with FDG-avidity. A clinical scoring system, ranged from 0 to 4, was developed by giving one score to 4 independent variables. A cut-off value of 2.5 showed good prediction of FDG-avidity in EGCs, with a sensitivity and specificity of 65.0% and 85.2%, respectively.F-FDG uptake by EGC depends on location, gross type, size, and depth of invasion of the primary tumor. A clinical scoring system based on clinicopathologic variables can predict the FDG-avidity of primary tumors in patients with EGC.

Hong CM, Jeong JH, Son SH, et al.
Serum thyroglobulin elevation after needle aspiration of the lymph nodes: the predictive value for detecting metastasis in papillary thyroid cancer patients - a pilot study.
Medicine (Baltimore). 2019; 98(31):e16461 [PubMed] Related Publications
Ultrasonography (USG)-guided fine needle aspiration (FNA) is widely used for diagnosis of lymph node (LN) metastasis in papillary thyroid cancer (PTC). However, FNA cytology sometimes shows inconclusive results. Recently, the measurement of thyroglobulin (Tg) in FNA washout fluid (aspirate-Tg) has been widely adopted, but there are some difficulties in the preparation of the sample and standardization of the procedure. Here, we examined serum Tg after FNA as a new predictive marker for LN metastasis of PTC. We performed USG-guided FNA cytology and examined aspirate-Tg in PTC patients showing suspicious metastatic LNs during follow-up. We measured baseline serum thyroid stimulating hormone (TSH), Tg, and Tg antibody levels before FNA, and serum Tg level within an hour after FNA. We defined aspirate-Tg level above 0.9 ng/mL as positive, and a 30% increase in serum Tg level after FNA compared to the baseline as elevation of serum Tg. Twenty-two patients were included in our study. Nine patients (40.9%) showed elevation of Tg level after FNA, and the mean value of Tg elevation was 24.8 ± 48.0 ng/mL. Among these 9 patients, 8 were diagnosed with PTC and 1 patient showed cellular atypia on cytopathology. All these patients showed positive aspirate-Tg. Thirteen patients (59.1%) did not show elevation of Tg level after FNA. Among these patients, 2 had PTC, 2 had cellular atypia, and 9 yielded negative results for malignancy on cytopathology. Elevation of serum Tg level after FNA might have a diagnostic role for predicting LN metastasis of PTC.

Cho O, Chun M, Kim SW, et al.
Lymphopenia as a Potential Predictor of Ipsilateral Breast Tumor Recurrence in Early Breast Cancer.
Anticancer Res. 2019; 39(8):4467-4474 [PubMed] Related Publications
BACKGROUND/AIM: The aim of this study was to investigate the association between lymphopenia after breast conserving therapy (BCT) and ipsilateral breast tumor recurrence (IBTR) in early breast cancer (EBC).
PATIENTS AND METHODS: We examined 216 EBC patients treated with partial mastectomy followed by radiotherapy (RT), none of whom received chemotherapy. Absolute lymphocyte counts (ALCs) during the two years after RT were collected from each patient: pretreatment ALC, ALC at 3-5 months (ALC1), ALC at 9-11 months, ALC at 15-17 months, and ALC at 21-23 months.
RESULTS: The 102 patients with ALC1 ≤1,479 cells/μl (defined as lymphopenia) had significantly higher 10-year IBTR rate than the 102 patients with ALC1 >1,479 cells/μl (16.2% vs. 1%, p=0.0034). The multivariate analysis showed that age, resection margins, human epidermal growth factor receptor, and lymphopenia were significant predictors of IBTR.
CONCLUSION: Lymphopenia is a potential predictor for IBTR in EBC patients treated with BCT.

An HJ, Song DH
Displacement of Vitamin D Receptor Is Related to Lower Histological Grade of Endometrioid Carcinoma.
Anticancer Res. 2019; 39(8):4143-4147 [PubMed] Related Publications
BACKGROUND/AIM: Vitamin D analogs have a protective effect on carcinogenesis in humans. Since vitamin D receptor (VDR) is detected in many histotypes of cancer, this study evaluated the role of VDR expression in endometrioid carcinoma.
MATERIALS AND METHODS: Tumor samples were collected from 60 patients who had undergone surgery, and the pattern of VDR expression assessed in tissue microarray (TMA) blocks of tumor samples. When VDR expression in the cytoplasm was higher than that in the nucleus, this was noted as 'displacement'. Using statistical analysis, the relationship between VDR expression and clinicopathological factors was evaluated.
RESULTS: Immunohistochemical staining of nuclear VDR was as follows: Negative: 32 (53.3%); mild: 13 (21.7%); moderate: 14 (23.3%); strong: 1 (1.7%). For cytoplasmic VDR expression: Negative: 2 (3.3%); mild: 19 (31.7%); moderate: 31 (51.7%); strong: 7 (11.7%). VDR displacement was found in 42 (70%) cores. VDR displacement was significantly positively correlated with endometrioid carcinoma having lower histological grade (1, p=0.03).
CONCLUSION: Displacement of VDR was significantly correlated with lower histological grade. Clinicians might be able to predict prognosis and decide therapies related to vitamin D analogs using this remarkable biomarker for endometrial carcinoma.

Yoon SN, Park JH, Lwin TM, et al.
Tumor-sealing Surgical Orthotopic Implantation of Human Colon Cancer in Nude Mice Induces Clinically-relevant Metastases Without Early Peritoneal Carcinomatosis.
Anticancer Res. 2019; 39(8):4065-4071 [PubMed] Related Publications
BACKGROUND: Surgical orthotopic implantation of human colon cancer tissue to the ceca of mice has been used to mimic behavior of cancer in human patients for the development of precision cancer medicine. However, with the current method of serosal surface implantation (SSI) of pieces of human colon cancer tissue, cancer cells are exposed to the peritoneum, which can artificially increase the rate of peritoneal carcinomatosis (PC) during the disease course. The objective of the present study was to introduce a tumor-sealing method (TSM) and compare it with SSI for the ability to produce clinically-relevant metastases without artificial PC.
MATERIALS AND METHODS: HCT116 colon cancer cells transfected with green fluorescence protein (GFP) were cultured and then injected into the subcutaneous layer of athymic nude mice. Subcutaneous tumors were allowed to grow sufficiently to supply adequate tumor for orthotopic implantation. For SSI, a 1 mm
RESULTS: At 20 days after implantation, PC rates in the SSI group and the TSM group were 80% (12/15) and 20% (3/15), respectively (p<0.001). The liver metastasis rate was 41.7% (5/12) in the SSI group and 50% (5/10) in the TSM group (p=0.696). The lung metastasis rate was 0% (0/12) in the SSI group and 10% (1/10) in the TSM group (p=0.201). The mean survival of mice without PC on the 20th day was significantly longer than that of mice with PC on the 20th day (69.1±14.7 vs. 44.5±12.4 days, p=0.001).
CONCLUSION: These results suggest that TSM might be a more patient-like and useful method as a model of metastatic colon cancer than SSI.

Kang BW, Baek DW, Kang H, et al.
Novel Therapeutic Approaches for Epstein-Barr Virus Associated Gastric Cancer.
Anticancer Res. 2019; 39(8):4003-4010 [PubMed] Related Publications
Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is classified as one of four GC subtypes by comprehensive molecular characterization. Though the mechanism of tumorigenesis by EBV infection has not yet been fully clarified, EBV infection might contribute to the malignant transformation of GC cells by involving various cellular processes and signaling pathways. EBVaGC has shown the following distinct characteristics in contrast to other subtypes: extreme DNA hypermethylation, recurrent phosphatidylinositol 4,5-biphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) mutations, overexpression of programmed cell death ligand 1/2 (PD-L1/2), and occasional immune cell signaling activation. Therefore, using these molecular features as guides, targeted agents need to be evaluated in clinical trials for EBVaGC. Accordingly, this review uses the best available evidence to focus on novel therapeutic approaches using the distinct pathologic characteristics of EBVaGC patients.

Oh SB, Seol YM, Kim HJ, Choi YJ
Retrospective evaluation of the efficacy and safety of rivaroxaban in patients with cancer-associated venous thromboembolism: A single-center study.
Medicine (Baltimore). 2019; 98(30):e16514 [PubMed] Related Publications
ABSTRCT: The purpose of this study was to evaluate the efficacy and safety of rivaroxaban for the treatment of cancer-associated venous thromboembolism (VTE).We performed a retrospective chart review of cancer patients with a pulmonary embolism, deep vein thrombosis, or both. Our analysis included all patients who received rivaroxaban from March 2013 to June 2016 at the Hemato-Oncology Division at the Pusan National University Hospital in Korea.Preliminary results identified 123 patients with a history of cancer that were treated with rivaroxaban. The average duration of rivaroxaban therapy was 95.25 days. While 35 patients had resolved VTE after the initiation of rivaroxaban, only one patient had it recur on rivaroxaban treatment. Major bleeding was observed in 6 (4.9%) patients and minor bleeding in 12 (9.8%) patients. The majority of bleeding events occurred spontaneously and most incidences of bleeding could be treated conservatively. Recurrence and major bleeding events on rivaroxaban were relatively low despite the fact that many patients had metastatic disease. Among 52 patient deaths (42.3%), none were due to VTE or bleeding complications; the cause of death in the majority of cases was cancer progression.Rivaroxaban is effective and safe for the treatment of cancer-associated VTE.

Shin J, Yu JH, Jin YJ, et al.
Effective therapeutic options for elderly patients with hepatocellular carcinoma: A nationwide cohort study.
Medicine (Baltimore). 2019; 98(30):e16150 [PubMed] Related Publications
We evaluated the post-treatment overall survival (OS) of elderly hepatocellular carcinoma (HCC) patients.The archived records of 10,578 HCC patients registered at the Korean Central Cancer Registry from 2008 through 2014 were retrospectively analyzed. In this registry, we selected Barcelona Clinic Liver Cancer (BCLC) 0, A, or B staged HCC patients (n = 4744) treated by surgical resection (SR), local ablation therapy (LAT), or locoregional therapy (LRT). OSs in nonelderly (<70 years) and elderly (≥70 years) patients were compared after propensity score matching (PSM).In BCLC 0-A staged HCC, the cumulative OS rates of elderly patients were poorer than those of nonelderly patients after PSM (P < .001), but not in those with BCLC stage B (P > .05). In BCLC 0-A staged elderly patients, OS after SR was significantly better than after LAT (P = .005) or LRT (P < .001). In BCLC B staged elderly patients, SR achieved better OS than LRT (P = .006). Multivariable analysis showed that LAT (hazard ratio [HR] 1.52, P = .048) or LRT (HR, 2.01, P < .001) as compared with SR, and large (>3 cm) tumor size (HR1.49, P = .018) were poor predictors of OS for elderly patients with BCLC stage 0-A, and that LRT (HR, 2.64, P = .042) was a poor predictor for those with BCLC stage B.SR provided a better OS rate than LAT or LRT in elderly HCC patients with BCLC stage 0-A, than LRT in those with BCLC stage B. SR should be considered the first therapeutic option even in elderly HCC patients with these stages.

Loriot Y, Necchi A, Park SH, et al.
Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.
N Engl J Med. 2019; 381(4):338-348 [PubMed] Related Publications
BACKGROUND: Alterations in the gene encoding fibroblast growth factor receptor (
METHODS: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified
RESULTS: A total of 99 patients in the selected-regimen group received a median of five cycles of erdafitinib. Of these patients, 43% had received at least two previous courses of treatment, 79% had visceral metastases, and 53% had a creatinine clearance of less than 60 ml per minute. The rate of confirmed response to erdafitinib therapy was 40% (3% with a complete response and 37% with a partial response). Among the 22 patients who had undergone previous immunotherapy, the confirmed response rate was 59%. The median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months. Treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments, were reported in 46% of the patients; 13% of the patients discontinued treatment because of adverse events. There were no treatment-related deaths.
CONCLUSIONS: The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with

Kwon SM, Ko Y, Bang SS
Primary intraosseous osteolytic meningioma: a case report and review of the literature.
BMC Neurol. 2019; 19(1):176 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary intraosseous meningioma is a subset of extradural meningioma that arises in the bone, and only a few cases have been reported to date.
CASE PRESENTATION: An 80-year-old man presented with decreased hearing on the right side accompanied by a disturbance of balance 10 months prior to admission. Magnetic resonance imaging revealed an 8 × 7 cm osteolytic mass in the right posterior fossa related to the petrous bone, with extension to the cervical region. During surgery, the tumor was found to be located extradurally, with no invasion of the dura. The tumor was removed entirely, apart from a small portion around the jugular foramen to avoid lower cranial nerve injury.
CONCLUSION: The final diagnosis was primary intraosseous osteolytic meningioma with atypical pathology. Here, we report a rare case of an osteolytic skull lesion in the skull base not invading the dura and with extensive bone destruction.

Kim KH, Ryu SY, Lee HY, et al.
Evaluating the tumor biology of lung adenocarcinoma: A multimodal analysis.
Medicine (Baltimore). 2019; 98(29):e16313 [PubMed] Related Publications
We evaluated the relationships among functional imaging modality such as PET-CT and DW-MRI and lung adenocarcinoma pathologic heterogeneity, extent of invasion depth, and tumor cellularity as a marker of tumor microenvironment.In total, 74 lung adenocarcinomas were prospectively included. All patients underwent 18F-fluorodeoxyglucose (FDG) PET-CT and MRI before curative surgery. Pathology revealed 68 stage I tumors, 3 stage II tumors, and 3 stage IIIA tumors. Comprehensive histologic subtyping was performed for all surgically resected tumors. Maximum standardized uptake value (SUVmax) and ADC values were correlated with pathologic grade, extent of invasion, solid tumor size, and tumor cellularity.Mean solid tumor size (low: 1.7 ± 3.0 mm, indeterminate: 13.9 ± 14.2 mm, and high grade: 30.3 ± 13.5 mm) and SUVmax (low: 1.5 ± 0.2, indeterminate: 3.5 ± 2.5, and high grade: 15.3 ± 0) had a significant relationship with pathologic grade based on 95% confidence intervals (P = .01 and P < .01, respectively). SUVmax showed a strong correlation with tumor cellularity (R = 0.713, P < .001), but was not correlated with extent of invasion (R = 0.387, P = .148). A significant and strong positive correlation was observed among SUVmax values and higher cellularity and pathologic grade. ADC did not exhibit a significant relationship with tumor cellularity.Intratumor heterogeneity quantification using a multimodal-multiparametric approach might be effective when tumor volume consists of a real tumor component as well as a non-tumorous stromal component.

Bang S, Chung K, Chung J, et al.
The erector spinae plane block for effective analgesia after lung lobectomy: Three cases report.
Medicine (Baltimore). 2019; 98(29):e16262 [PubMed] Related Publications
RATIONALE: The thoracic epidural block and thoracic paravertebral block are widely used techniques for multimodal analgesia after thoracic surgery. However, they have several adverse effects, and are not technically easy. Recently, the erector spinae plane block (ESPB), an injected local anesthetic deep to the erector spinae muscle, is a relatively simple and safe technique.
PATIENT CONCERNS: Three patients were scheduled for video assisted thoracoscopic lobectomy with mediastinal lymph node dissection. All the patients denied any past medical history to be noted.
DIAGNOSES: They were diagnosed with primary adenocarcinoma requiring lobectomy of lung.
INTERVENTIONS: The continuous ESPB was performed at the level of the T5 transverse process. The patient was received the multimodal analgesia consisted of oral celecoxib 200 mg twice daily, intravenous patient-controlled analgesia (Fentanyl 700 mcg, ketorolac 180 mg, total volume 100 ml), and local anesthetic (0.375% ropivacaine 30 ml with epinephrine 1:200000) injection via indwelling catheter every 12 hours for 5 days. Additionally, we injected a mixture of ropivacaine and contrast through the indwelling catheter for verifying effect of ESPB and performed Computed tomography 30 minutes later.
OUTCOMES: The pain score was maintained below 3 points for postoperative 5 days, and no additional rescue analgesics were administered during this period. In the computed tomography, the contrast spread laterally from T2-T12 deep to the erector spinae muscle. On coronal view, the contrast spread to the costotransverse ligament connecting the rib and the transverse process. In the 3D reconstruction, the contrast spread from T6-T10 to the costotransverse foramen.
LESSONS: Our contrast imaging data provides valuable information about mechanism of ESPB from a living patient, and our report shows that ESPB can be a good option as a multimodal analgesia after lung lobectomy.

Bishayee K, Habib K, Sadra A, Huh SO
Targeting the Difficult-to-Drug CD71 and MYCN with Gambogic Acid and Vorinostat in a Class of Neuroblastomas.
Cell Physiol Biochem. 2019; 53(1):258-280 [PubMed] Related Publications
BACKGROUND/AIMS: Although neuroblastoma is a heterogeneous cancer, a substantial portion overexpresses CD71 (transferrin receptor 1) and MYCN. This study provides a mechanistically driven rationale for a combination therapy targeting neuroblastomas that doubly overexpress or have amplified CD71 and MYCN. For this subset, CD71 was targeted by its natural ligand, gambogic acid (GA), and MYCN was targeted with an HDAC inhibitor, vorinostat. A combination of GA and vorinostat was then tested for efficacy in cancer and non-cancer cells.
METHODS: Microarray analysis of cohorts of neuroblastoma patients indicated a subset of neuroblastomas overexpressing both CD71 and MYCN. The viability with proliferation changes were measured by MTT and colony formation assays in neuroblastoma cells. Transfection with CD71 or MYCN along with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect expression changes. For pathway analysis, gene ontology (GO) and Protein-protein interaction analyses were performed to evaluate the potential mechanisms of GA and vorinostat in treated cells.
RESULTS: For both GA and vorinostat, their pathways were explored for specificity and dependence on their targets for efficacy. For GA-treated cells, the viability/proliferation loss due to GA was dependent on the expression of CD71 and involved activation of caspase-3 and degradation of EGFR. It relied on the JNK-IRE1-mTORC1 pathway. The drug vorinostat also reduced cell viability/proliferation in the treated cells and this was dependent on the presence of MYCN as MYCN siRNA transfection led to a blunting of vorinostat efficacy and conversely, MYCN overexpression improved the vorinostat potency in those cells. Vorinostat inhibition of MYCN led to an increase of the pro-apoptotic miR183 levels and this, in turn, reduced the viability/proliferation of these cells. The combination treatment with GA and vorinostat synergistically reduced cell survival in the MYCN and CD71 overexpressing tumor cells. The same treatment had no effect or minimal effect on HEK293 and HEF cells used as models of non-cancer cells.
CONCLUSION: A combination therapy with GA and vorinostat may be suitable for MYCN and CD71 overexpressing neuroblastomas.

Kim MS, Park JH, Kim JY, et al.
Upper gastrointestinal bleeding caused by direct invasion of diffuse large B-cell lymphoma into the stomach in a patient with HIV infection: A case report.
Medicine (Baltimore). 2019; 98(28):e16363 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Diffuse large B-cell lymphoma (DLBCL) is the most frequent human immunodeficiency virus (HIV)-related Non-Hodgkin's Lymphoma of the stomach. Although gastrointestinal (GI) bleeding due to primary gastric lymphoma has been previously reported in the literature, there have been no reports of stomach wall involvement of intra-abdominal lymphoma presenting as GI bleeding.
PATIENT CONCERNS: We present a rare case of direct invasion of DLBCL to the stomach wall that presented as upper GI bleeding in a patient with HIV.
DIAGNOSIS: Upper endoscopy showed a large ulcerofungating mass in the lesser curvature of upper stomach body. The computed tomography scan showed an about 22 × 12 cm sized huge mass that invades into the stomach wall in the abdominal cavity. A diagnosis of DLBCL was established after histological examination.
INTERVENTION: The patient was treated with 6 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).
OUTCOMES: The patient achieved a complete response with 6 courses of R-CHOP treatment. No recurrence was observed during the 4-month follow-up period.
LESSONS: Because of the high incidence of lymphoma in patients with HIV, if such patients complain of dyspepsia, epigastric soreness, or melena, malignant tumors, such as lymphomas or stomach cancers, should be suspected. As in this patient, doctors should be aware that intra-abdominal lymphoma can invade into the stomach wall and cause bleeding.

Choi HS, Lee SH, Lee YJ, Ha IH
Nonsurgical integrative Korean Medicine treatment of discal cyst: A case report and a retrospective chart review analysis.
Medicine (Baltimore). 2019; 98(27):e16189 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Discal cysts are rare lesions characterized by pain caused by neurogenic compression with similar symptoms as those of disc herniation. This study aims to report the spontaneous regression of discal cyst achieved through nonsurgical integrative Korean Medicine treatment and the clinical epidemiological features of discal cyst cases collected from 4 institutions.
PATIENT CONCERNS: A 31-year-old woman had low back pain and radiating pain equivalent to a numeral rating scale (NRS) of 8 and had limitations in daily work and activities.
DIAGNOSES: The patient was diagnosed as having discal cysts that compressed the left S1 based on findings of L-spine magnetic resonance imaging (MRI) performed at our hospital.
INTERVENTIONS: The patient received nonsurgical Korean Medicine treatment and after 24 days of treatment in the hospital, she underwent 16 additional treatments as an outpatient.
OUTCOMES: Spontaneous regression was confirmed in the L-spine MRI follow-up at 36 days and 99 days after the initial test, and the patient underwent once-a-week follow up to examine NRS, Oswestry Disability Index (ODI), EuroQol-5 Dimensions (EQ-5D), and fear-avoidance beliefs questionnaire (FABQ) after 4 weeks, and 2, 3, and 6-month follow-ups after that. The patient was discharged in a painless condition, and she was able to carry on for 5 months without increased pain.
LESSONS: Discal cysts are more rapid progress than disc herniation, it seems valid to attempt nonsurgical treatment. Epidemiologically, this is the first study to present the clinical epidemiological characteristics of discal cysts, it would provide valuable information to clinicians who treat and study discal cysts.

Kim HY, Kim ST, Kim HJ, et al.
Differentiation of postoperative changes and residual tumors in dynamic contrast-enhanced sella MRI after transsphenoidal resection of pituitary adenoma.
Medicine (Baltimore). 2019; 98(27):e16089 [PubMed] Free Access to Full Article Related Publications
To establish magnetic resonance imaging (MRI) features that differentiate residual tumors from postoperative surgical changes following the transsphenoidal approach of a pituitary adenoma.We analyzed residual enhancements at the tumor bed in 52 patients who underwent dynamic contrast-enhanced sella MRI within 48 hours after surgery and at 6 to 28 months. Patients were divided into 2 groups defined by either peripheral or nodular enhancement patterns. For each group, we measured the maximum thickness of the residual enhancing portion and compared differences in the residual tumor and postoperative changes.Among the tumors examined in the 52 patients, 19 residual tumors showed nodular (n = 16) and peripheral (n = 3) enhancement patterns, and 33 postoperative changes showed nodular (n = 3) and peripheral (n = 30) enhancement patterns. The mean residual tumor thickness was 7.1 mm (range, 2.9-16.8 mm) and 1.9 mm (range, 1.0-7.4 mm) in the postoperative change. Receiver operating characteristic curve analysis revealed that a 3.9-mm thickness was associated with 89% sensitivity, 97% specificity, and 94% accuracy for diagnosis of residual tumor.On immediate postoperative MRI, residual enhancement with greater than 3.9-mm thickness and nodular pattern suggest residual pituitary adenoma tumor.

Kim BY, Cho KR, Sohn JH, Kim JY
Sarcomatoid carcinoma after radiotherapy for early-stage oral squamous cell carcinoma: Case report.
Medicine (Baltimore). 2019; 98(27):e16003 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Sarcomatoid carcinoma is a rare variant of squamous cell carcinoma (SCC) with poor prognosis. Previous radiation has been reported as one of the etiologic factors.
PATIENT CONCERNS: We describe a case of a 57-year-old man presented with a painless mass in the left supraclavicular area. Five years before, he was diagnosed with SCC in floor of mouth (FOM) and underwent radiotherapy (RT).
DIAGNOSES: Sonography-guided biopsy on the supraclavicular lymph node revealed diffuse spindle cell proliferation with a focus of squamous differentiation. Local recurrence on primary site or distant metastasis was not obvious on both computed tomography (CT) of the neck and F-fluorodeoxyglucose positron emission tomography CT. The final diagnosis was confirmed as sarcomatoid carcinoma via surgery.
INTERVENTIONS: The patient underwent surgery including explorative resection of the mouth floor, excision of the submandibular gland, and modified radical neck dissection. Following surgery, the patient received adjuvant radiation therapy.
OUTCOMES: There were no complications according to the surgery. Six months after adjuvant therapy, distant metastasis to liver was identified. The patient is currently undergoing palliative chemotherapy.
LESSONS: This may be the first reported case of sarcomatoid carcinoma arising from early-stage SCC in FOM that was previously treated with RT alone. When RT is performed as a single modality for oral SCC, even in an early stage, rigorous follow-up should be performed.

Min JY, Jo H, Roh K, Chung MY
Preventing deoxygenation with high flow nasal cannula oxygen during induction of general anesthesia for rigid bronchoscopy: Two case reports.
Medicine (Baltimore). 2019; 98(27):e15998 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Rigid bronchoscopy under general anesthesia enables performing diagnostic and/or therapeutic procedures in the tracheobronchial tree. As most patients undergoing rigid bronchoscopy have moderate to severe respiratory disease or central airway obstruction, the operators often face the risk of hypoxemia when inserting the rigid bronchoscope into the patients' airway. Applying high flow nasal cannula (HFNC) oxygen therapy before the insertion of the bronchoscope allows to maintain high fractional inspired oxygen (FiO2) and thus leading to maximizing apnea time before desaturation.
PATIENT CONCERNS AND DIAGNOSIS: Case 1: A 70-year-old female patient was diagnosed with lung cancer in the left lower lobe and a tracheal mass of about 2.6 cm * 0.8 cm in size.Case 2: A male patient, 77 years old, 55.7 kg and 157.3 cm in height, had been diagnosed with chronic obstructive pulmonary disease, and was scheduled for the bronchoscopic volume reduction surgery upon exacerbation of his symptoms of dyspnea and cough with sputum.
INTERVENTIONS: Preoxygenation was performed with HFNC (Fisher&Paykel Optiflow Thrive, New Zealand) for 3 minutes before the administration of anesthetic medications. The oxygen flow was set at 50 L/min and the FiO2 at 1.0. SpO2 increased to 100%.
OUTCOMES: The HFNC oxygen has shown its effectiveness in safely maintaining the patients' SpO2 during the prolonged apneic period of inserting bronchoscope.
LESSONS: HFNC oxygen is an effective tool in oxygenating the patients during the induction of rigid bronchoscopy, and that it may be a superior alternative to the conventional method of preoxygenation.

Hwang JE, Kim H, Shim HJ, et al.
Lymph-node ratio is an important clinical determinant for selecting the appropriate adjuvant chemotherapy regimen for curative D2-resected gastric cancer.
J Cancer Res Clin Oncol. 2019; 145(8):2157-2166 [PubMed] Related Publications
PURPOSE: Adjuvant chemotherapy for gastric cancer, particularly stage III, improves survival after curative D2 gastrectomy. We investigated the clinical value of the lymph-node ratio (LNR; number of metastatic lymph nodes/number of lymph nodes examined) for selecting the appropriate adjuvant chemotherapy regimen in patients with D2-resected stage II/III gastric cancer.
METHODS: We reviewed the data of 819 patients who underwent curative D2 gastrectomy followed by adjuvant chemotherapy. Of them, 353 patients received platinum-based chemotherapy and 466 received TS-1. The patients were categorized into three groups according to their LNR (LNR 1, 0-0.1; LNR 2, > 0.1-0.25; and LNR 3, > 0.25), and their disease-free survival (DFS) was evaluated.
RESULTS: The DFS curves of the patients were well separated according to stage and LNR. In multivariate analyses, an LNR > 0.1 was strongly associated with the 3-year DFS (hazard ratio 2.402, 95% confidence interval 1.607-3.590, P < 0.001). Platinum-based chemotherapy improved the 3-year DFS compared to TS-1 in patients with LNR 3 group in stage III gastric cancer (platinum vs. TS-1, median DFS 26.87 vs. 16.27 months, P = 0.028). An LNR > 0.1 was associated with benefiting from platinum-based adjuvant chemotherapy in stage III gastric cancer patients with lymphovascular invasion (platinum vs. TS-1, median DFS 47.57 vs. 21.77 months, P = 0.011).
CONCLUSIONS: The LNR can be used to select the appropriate adjuvant chemotherapy regimen for patients with D2-resected gastric cancer, particularly in stage III.

Park K, Baek Y, Lee JL
Random Allocated Study of Wrapping Oblate for Prevention of Everolimus-associated Stomatitis in Patients With Metastatic Renal Cell Carcinoma.
Anticancer Res. 2019; 39(7):3937-3944 [PubMed] Related Publications
BACKGROUND: The study aim was to evaluate the efficacy of wrapping oblate for prevention of everolimus-associated stomatitis in metastatic renal cell carcinoma (mRCC).
PATIENTS AND METHODS: Patients with mRCC prescribed everolimus after failure of vascular endothelial growth factor-tyrosine kinase inhibitor were enrolled. Patients were consecutively assigned to take everolimus covered with or without oblate. The primary end-points were the incidence of and time to grade 2 or more stomatitis. Additionally, we assessed whether grade 2 or more stomatitis that occurred in the non-oblate group could be prevented with crossover application of oblate.
RESULTS: This study included 79 patients [oblate group: 42(53%); non-oblate group: 37(47%)]. Thirty (38%) patients developed grade 2 or more stomatitis [incidence: oblate group, 31% (13/42); non-oblate group, 46% (17/37), p=0.245; median time to grade 2 or more stomatitis: oblate group, not reached; non-oblate group, 6.0 months, p=0.251]. Among 10 patients who developed grade 2 or more stomatitis in the non-oblate group and received oblate-covered everolimus, nine (90%) showed complete recovery or improved to grade 1, which persisted until discontinuation of everolimus.
CONCLUSION: Oblate-covered everolimus improved the incidence of and time to grade 2 or more stomatitis, although it was not statistically significantly different compared to the non-oblate group. Oblate wrapping prevented recurrence of grade 2 or more stomatitis in patients who took uncovered everolimus and developed significant stomatitis.

Sung PS, Yang K, Bae SH, et al.
Reduction of Intrahepatic Tumour by Hepatic Arterial Infusion Chemotherapy Prolongs Survival in Hepatocellular Carcinoma.
Anticancer Res. 2019; 39(7):3909-3916 [PubMed] Related Publications
BACKGROUND/AIM: This study aimed to identify the survival benefit of intrahepatic tumour control by hepatic arterial infusion chemotherapy (HAIC) in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombus (PVTT) or extrahepatic metastasis.
PATIENTS AND METHODS: Between 2010 and 2017, a total of 187 consecutive patients with advanced HCC were treated with HAIC. The survival outcomes and response rates to HAIC were analysed.
RESULTS: The intrahepatic objective response (OR) rate of all enrolled patients was 18.7%. The survival outcome of patients with OR was significantly better from those without OR, irrespective of initial distant metastasis. Achievement of intrahepatic OR by HAIC and favourable liver function at the time of best response evaluation were two independent factors associated with better OS.
CONCLUSION: HAIC-induced intrahepatic tumour reduction significantly prolonged patient survival, irrespective of PVTT or initial distant metastasis.

Liu Y, Kwon T, Kim JS, et al.
Peroxiredoxin V Reduces β-Lapachone-induced Apoptosis of Colon Cancer Cells.
Anticancer Res. 2019; 39(7):3677-3686 [PubMed] Related Publications
BACKGROUND/AIM: Peroxiredoxin (Prx) V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS). Also, Prx V has been shown to mediate cell apoptosis in various cancers. However, the mechanism of Prx V-induced apoptosis in colon cancer cells remains unknown. Thus, in this study we analyzed the effects of Prx V in β-lapachone-induced apoptosis in SW480 human colon cancer cells.
MATERIALS AND METHODS: β-lapachone-induced apoptosis was analyzed by the MTT assay, western blotting, fluorescence microscopy, Annexin V staining and flow cytometry.
RESULTS: Overexpression of Prx V, significantly decreased β-lapachone-induced cellular apoptosis and Prx V silencing increased β-lapachone-induced cellular apoptosis via modulating ROS scavenging activity compared to mock SW480 cells. In addition, to further explore the mechanism of Prx V regulated β-lapachone-induced SW480 cells apoptosis, the Wnt/β-catenin signaling was studied. The Wnt/ β-catenin signaling pathway was found to be induced by β-lapachone.
CONCLUSION: Prx V regulates SW480 cell apoptosis via scavenging ROS cellular levels and mediating the Wnt/β-catenin signaling pathway, which was induced by β-lapachone.

Kim JY, Park G, Krishnan M, et al.
Selective Wnt/β-catenin Small-molecule Inhibitor CWP232228 Impairs Tumor Growth of Colon Cancer.
Anticancer Res. 2019; 39(7):3661-3667 [PubMed] Related Publications
BACKGROUND/AIM: To explore the possibility of a selective small-molecule β-catenin inhibitor, CWP232228, as a potential therapeutic drug in the treatment of colorectal cancer (CRC).
MATERIALS AND METHODS: The effect of CWP2228 on HCT116 cells was analysed in vitro via flow cytometry, western immunoblotting, and luciferase reporter assays. NOD-scid IL2Rgamma
RESULTS: CWP232228 treatment decreased the promoter activity and nuclear expression of β-catenin and induced a significant cytotoxic effect in HCT116 cells. CWP232228 treatment induced apoptosis and cell-cycle arrest in the G
CONCLUSION: Collectively, CWP232228 may be used as a potential therapeutic drug in CRC.

Namgung Y, Kim SY, Kim I
Down-regulation of Survivin by BIX-01294 Pretreatment Overcomes Resistance of Hepatocellular Carcinoma Cells to TRAIL.
Anticancer Res. 2019; 39(7):3571-3578 [PubMed] Related Publications
BACKGROUND/AIM: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cancer-selective, cell-death-inducing agent with little toxicity to normal cells. However, various human cancers and cancer cell lines have been reported to be resistant to TRAIL. Molecular clarification of resistance mechanism is needed.
MATERIALS AND METHODS: Compound screening, proliferation assays, western blotting, and flow cytometry were used to examine the sensitizer activity of methyl transferase inhibitor BIX-01294 in combination with TRAIL, in hepatocellular carcinoma (HCC) cells. RNA sequencing analysis and single guide (sg)RNA-mediated gene deletion were used to investigate the role of survivin in sensitization.
RESULTS: In HCC cells, BIX-01294 enhanced TRAIL sensitivity by reducing survivin expression at the RNA level. Small interference RNA-mediated gene knockdown demonstrated the mechanism of sensitization to be via the reduction of survivin.
CONCLUSION: Euchromatin histone methyltransferase 2 (EHMT2) inhibition by BIX-01294 may be a potent anti-tumor therapeutic strategy for human HCC.

Seo YS, Kim TH, Lim H, et al.
Phenformin Induces Caspase-dependent Apoptosis of FaDu Head and Neck Squamous Cell Carcinoma Cells.
Anticancer Res. 2019; 39(7):3499-3506 [PubMed] Related Publications
BACKGROUND/AIM: The present study aimed to investigate the apoptotic effects of phenformin, a therapeutic agent for diabetes, on head and neck squamous cell carcinoma (HNSCC).
MATERIALS AND METHODS: Cytotoxicity was measured by the MTT and live/dead cell assay. Phenformin-induced apoptotic FaDu cell death and its associated cellular signaling pathways were investigated by hematoxylin and eosin staining, 4',6-diamidino-2-phenylindole staining, caspase-3 activity assay, fluorescence-activated cell sorting analysis, and western blotting.
RESULTS: Phenformin promoted death of and apoptotic processes in FaDu cells, including morphological alterations and nuclear condensation. Furthermore, treatment with phenformin increased caspase-3 activity and apoptotic populations via the caspase cascade through cleavage of capspase-8, -9, and -3 and poly(ADP-ribose) polymerase in FaDu cells. Moreover, phosphorylation levels of mitogen-activated protein kinases, nuclear factor-κB, and AKT were down-regulated in FaDu cells by phenformin.
CONCLUSION: Phenformin induced death of FaDu cells via caspase-dependent extrinsic and intrinsic apoptosis pathways and is a promising novel therapeutic agent for HNSCC.

Park JH, Zhao M, Oshiro H, et al.
Peritoneal Metastases in a Patient-derived Orthotopic Xenograft (PDOX) Model of Colon Cancer Imaged Non-invasively
Anticancer Res. 2019; 39(7):3463-3467 [PubMed] Related Publications
BACKGROUND/AIM: Patient-derived orthotopic xenograft (PDOX) models have patient-like clinical features and may be imaged, in case of some cancers, by passaging of the tumors through transgenic nude mice expressing red-fluorescent protein (RFP) where they stably acquire RFP expressing stroma. The aim of the present study was to quantify red fluorescent area and intensity in colon-cancer peritoneal metastases in PDOX models in non-transgenic nude mice after passage in RFP transgenic nude mice by non-invasive external fluorescence imaging.
MATERIALS AND METHODS: Tumor fragments originating from a colon cancer patient with peritoneal metastases were implanted in transgenic RFP nude mice. Resultant tumors were harvested, and fragments were implanted in the same strain a second time. Passaged tumors stably acquired RFP-expressing stroma from their transgenic hosts. The tumor with RFP-expressing stromal cells were harvested and implanted orthotopically in non-transgenic nude mice. At eight weeks post-implantation, non-invasive external RFP images were obtained. RFP area and intensity were measured and correlated with tumor weight and volume.
RESULTS: Metastatic patient colon cancer can be stably and brightly labeled by passage in transgenic RFP-expressing nude mice such that tumor growth could be non-invasively imaged. Tumor growing could be non-invasively imaged when passaged to non-transgenic nude mice. A strong correlation between fluorescence intensity and area values with tumor weight and volume were established by external fluorescence imaging.
CONCLUSION: This new tumor model of metastatic colon cancer can be used to evaluate novel therapeutics in real time for this recalcitrant disease.

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