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1.  Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2011 
Purpose
This study aimed to report nationwide cancer statistics in Korea, including incidence, mortality, survival, and prevalence, and their trends.
Materials and Methods
Incidence data from 1993 to 2011 were obtained from the Korea National Cancer Incidence Database, and vital status was followed through December 31, 2012. Mortality data from 1983 to 2011 were obtained from Statistics Korea. Crude and age-standardized rates for incidence, mortality, and prevalence, and relative survival were calculated.
Results
A total of 218,017 cancer cases and 71,579 cancer deaths were reported to have occurred in 2011, and there were 1,097,253 prevalent cases identified in Korea as of January 1, 2012. Over the past 13 years (1999-2011), overall incidence rates have increased by 3.4% per year. The incidence rates of liver and cervical cancers have decreased, while those of thyroid, breast, prostate, and colorectal cancers have increased. Notably, thyroid cancer increased by 23.3% per year in both sexes, and became the most common cancer since 2009. The mortality for all cancers combined decreased by 2.7% per year from 2002 to 2011. Five-year relative survival rates of patients diagnosed in the last 5 years (2007-2011) have improved by 25.1% compared with those from 1993 to 1995.
Conclusion
Overall cancer mortality rates have declined since 2002 in Korea, while incidence has increased rapidly and survival has improved.
doi:10.4143/crt.2014.46.2.109
PMCID: PMC4022819  PMID: 24851102
Incidence; Mortality; Survival; Prevalence; Neoplasms; Korea
2.  Prediction of Cancer Incidence and Mortality in Korea, 2014 
Purpose
We studied and reported on cancer incidence and mortality rates as projected for the year 2014 in order to estimate Korea's current cancer burden.
Materials and Methods
Cancer incidence data from 1999 to 2011 were obtained from the Korea National Cancer Incidence Database, and cancer mortality data from 1993 to 2012 were acquired from Statistics Korea. Cancer incidence in 2014 was projected by fitting a linear regression model to observed age-specific cancer incidence rates against observed years, then multiplying the projected age-specific rates by the age-specific population. For cancer mortality, a similar procedure was employed, except that a Joinpoint regression model was used to determine at which year the linear trend changed significantly.
Results
A total of 265,813 new cancer cases and 74,981 cancer deaths are expected to occur in Korea in 2014. Further, the crude incidence rate per 100,000 of all sites combined will likely reach 524.7 and the age-standardized incidence rate, 338.5. Meanwhile, the crude mortality rate of all sites combined and age-standardized rate are projected to be 148.0 and 84.6, respectively. Given the rapid rise in prostate cancer cases, it is anticipated to be the fourth most frequently occurring cancer site in men for the first time.
Conclusion
Cancer has become the most prominent public health concern in Korea, and as the population ages, the nation's cancer burden will continue to increase.
doi:10.4143/crt.2014.46.2.124
PMCID: PMC4022820  PMID: 24851103
Incidence; Mortality; Neoplasms; Forecasting; Korea; 2014
3.  A Nationwide Survey of Knowledge of and Compliance with Cancer Pain Management Guidelines by Korean Physicians 
Purpose
Although cancer pain is prevalent, under-treatment still remains a problem. Knowledge of and compliance with guidelines for management of cancer pain were analyzed for exploration of physician-related barriers to cancer pain management. In addition, physicians' knowledge and its correlation with cancer pain control were audited.
Materials and Methods
From July 8 to December 2, 2010, a nationwide survey of house staff enquired about their knowledge of cancer pain control guidelines, and the medical records of patients under their care were analyzed.
Results
In total, 180 physicians participated in the study. Their average score for knowledge was 14.6 (range, 7 to 19; maximum possible, 20). When the knowledge score was divided into low, medium, and high scores, patients receiving care from physicians with high levels of knowledge tended to have better cancer pain control (p<0.001). Of the total patients with severe pain, 19.5% were not prescribed strong opioids, and 40% were not prescribed any medication for breakthrough pain.
Conclusion
Physicians' knowledge of guidelines for control of cancer pain showed an association with improvement of pain management. Overall adherence to the guidelines was lacking. Continuous interventions such as education and audits regarding cancer pain control guidelines for physician are needed.
doi:10.4143/crt.2014.46.2.131
PMCID: PMC4022821  PMID: 24851104
Pain; Neoplasms; Knowledge; Analgesics; Guideline; Compliance
4.  Clinical Features and Treatment of Collecting Duct Carcinoma of the Kidney from the Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee 
Purpose
Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis.
Materials and Methods
From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases.
Results
Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months.
Conclusion
CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.
doi:10.4143/crt.2014.46.2.141
PMCID: PMC4022822  PMID: 24851105
Renal cell carcinoma; Kidney; Treatment; Prognosis
5.  Impact on Loco-regional Control of Radiochemotherapeutic Sequence and Time to Initiation of Adjuvant Treatment in Stage II/III Rectal Cancer Patients Treated with Postoperative Concurrent Radiochemotherapy 
Purpose
This study was designed to evaluate the impact of radiochemotherapeutic sequence and time to initiation of adjuvant treatment on loco-regional control for resected stage II and III rectal cancer.
Materials and Methods
Treatment outcomes for rectal cancer patients from two hospitals with different sequencing strategies regarding adjuvant concurrent radiochemotherapy (CRCT) were compared retrospectively. Pelvic radiotherapy was administered concurrently on the first (early CRCT, n=180) or the third cycle of chemotherapy (late CRCT, n=180). During radiotherapy, two cycles of fluorouracil were provided to patients in both groups. In the early CRCT group, median six cycles of fluorouracil and leucovorin were prescribed during the post-CRCT period. In the late CRCT group, two cycles of fluorouracil were administered in the pre- and post-CRCT periods.
Results
No significant differences in the 5-year loco-regional recurrence-free survival (LRRFS) (92.5% vs. 95.6%, p=0.43) or overall survival and disease-free survival were observed between groups. Patients who began receiving adjuvant treatment later than five weeks after surgery had lower LRRFS than patients who received adjuvant treatment within five weeks following surgery (79% vs. 91%, p<0.01). The risk of loco-regional recurrence increased as the time to initiation of adjuvant treatment was delayed.
Conclusion
In the current study, treatment outcomes were not significantly influenced by the sequence of adjuvant treatment but by the delay of adjuvant treatment for more than five weeks. Timely administration of adjuvant treatment is deemed important in achieving loco-regional tumor control for stage II/III rectal cancer patients.
doi:10.4143/crt.2014.46.2.148
PMCID: PMC4022823  PMID: 24851106
Adjuvant chemoradiotherapy; Sequence; Prognosis; Rectal neoplasms
6.  Clinical Outcomes of Local Excision Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer 
Purpose
To evaluate the treatment outcomes of local excision following preoperative chemoradiotherapy in patients with locally advanced rectal cancer who have not undergone radical surgery for any reason.
Materials and Methods
The data of 27 patients with locally advanced rectal cancer who underwent preoperative chemoradiotherapy followed by local excision were analyzed retrospectively. The primary endpoint was the 5-year relapse-free survival rate, and the secondary endpoint was the pattern of recurrence.
Results
The median follow-up time was 81.8 months (range, 28.6 to 138.5 months). The 5-year local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), relapse-free survival (RFS), and overall survival (OS) were 88.9%, 81.1%, 77.8%, and 85.0%, respectively. Six (22%) patients developed treatment failure; one (4%) patient had local recurrence only, three (11%) patients had distant recurrence only, and two (7%) patients had both. The 5-year LRFS, DMFS, RFS, and OS for patients with ypT0-1 compared with ypT2-3 were 94.1% vs. 77.8% (p=0.244), 94.1% vs. 55.6% (p=0.016), 88.2% vs. 55.6% (p=0.051), and 94.1% vs. 66.7% (p=0.073), respectively.
Conclusion
Local excision following preoperative chemoradiotherapy may be an alternative treatment for highly selected patients with locally advanced rectal cancer who have achieved ypT0-1 after preoperative chemoradiotherapy.
doi:10.4143/crt.2014.46.2.158
PMCID: PMC4022824  PMID: 24851107
Rectal neoplasms; Local excision; Preoperative chemoradiotherapy; Survival
7.  Metabolic Burden Measured by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Is a Prognostic Factor in Patients with Small Cell Lung Cancer 
Purpose
Evidence regarding the usefulness of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in predicting the prognosis of non-small cell lung cancer is increasing. However, data on small cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the prognostic value of metabolic parameters measured using 18F-FDG PET/CT in patients with SCLC.
Materials and Methods
We conducted a retrospective review of 114 patients with pathologically proven SCLC (26 cases of limited disease and 88 cases of extensive disease) who underwent pretreatment 18F-FDG PET/CT. The maximal SUV (SUVmax) was used quantitatively for determination of FDG PET activity. The SUVmax of the primary tumor (primary SUVmax), the sum of SUVmax values of malignant lesions (SUVsum), and the mean SUVmax of malignant lesions were calculated.
Results
The patient population was subdivided using a median SUVsum value of 24.6. High SUVsum showed a significant association with known factors for poor prognosis, including higher neuron-specific enolase (p=0.010), CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high SUVsum had significantly shorter median overall survival (6.6 months vs. 13.0 months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months, p<0.001) than patients with low SUVsum. Results of multivariate analysis showed that SUVsum, chemotherapy cycles, and the response to first-line treatment were significant prognostic factors of survival. In contrast, mean SUVmax and primary SUVmax were not significant predictors of survival.
Conclusion
In this study, metabolic burden represented by SUVsum from pretreatment 18F-FDG PET/CT was an independent prognostic factor in patients with SCLC.
doi:10.4143/crt.2014.46.2.165
PMCID: PMC4022825  PMID: 24851108
Small cell lung carcinoma; Tumor burden; Neoplasms; Prognosis; Positron-emission tomography and computed tomography
8.  Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment 
Purpose
There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC.
Materials and Methods
We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy.
Results
The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death.
Conclusion
Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.
doi:10.4143/crt.2014.46.2.172
PMCID: PMC4022826  PMID: 24851109
Urothelial carcinoma; M-VAC protocol; Second-line; Cisplatin failure
9.  Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion 
Purpose
The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE).
Materials and Methods
Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA).
Results
The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%.
Conclusion
The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.
doi:10.4143/crt.2014.46.2.178
PMCID: PMC4022827  PMID: 24851110
Adenocarcinoma; Lung; miR-134; miR-185; miR-22; Pleural effusion
10.  Preclinical Efficacy Testing for Stomach and Liver Cancers 
Purpose
Hollow fiber assays offer an early in vivo method of anticancer drug screening. The assays have been optimized for human cancers originating from the lung, breast, colon, ovary, and brain, but not from the stomach and liver. The current study focused on optimization of hollow fiber assays for gastric and hepatocellular carcinoma cell lines.
Materials and Methods
Gastric (SNU-16, SNU-484, SNU-668) and hepatocellular (HepG2, SK-Hep-1, Hep3B) carcinoma cell lines in hollow fibers were transplanted subcutaneously and intraperitoneally into mice, which were subsequently treated with a standard anticancer agent, paclitaxel. The hollow fiber activity of paclitaxel in each cell line was compared with the xenograft activity.
Results
Using optimized inoculation densities and schedules, treatment with paclitaxel was effective in gastric carcinoma cell lines, SNU-16 and SNU-484, but not in SNU-668. In the hollow fiber assays, paclitaxel was effective in hepatocellular carcinoma cell lines, HepG2 and SK-Hep-1, but not in Hep3B. Consistent with the results of the hollow fiber assay, SNU-16 and SNU-484, but not SNU-668, showed tumor regression, and HepG2 and SK-Hep-1, but not Hep3B, showed effective tumor responses following treatment with paclitaxel in xenograft models. When EW7197, a novel compound, and flavopiridol were tested in SNU-16 cells under optimized conditions, the hollow fiber activity showed good correlation with the xenograft activity of each compound.
Conclusion
Our protocols may be useful for screening candidate small molecules that may exhibit activity against stomach and liver cancers, both of which are common in Korea.
doi:10.4143/crt.2014.46.2.186
PMCID: PMC4022828  PMID: 24851111
Hollow fiber assay; Xenograft model antitumor assay; Stomach neoplasms; Liver neoplasms
11.  Case Series of Different Onset of Skin Metastasis According to the Breast Cancer Subtypes 
We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.
doi:10.4143/crt.2014.46.2.194
PMCID: PMC4022829  PMID: 24851112
Breast neoplasms; Skin neoplasms; Heteogeneity; Subtype
12.  Intra-tumoral Metastatic Double Primary Carcinoma: Synchronous Metastatic Tumor in Lung from Breast and Thyroid Carcinoma 
Cases of phenotypic heterogeneity of cells within tumors have recently been reported. Here, we report on a patient with characteristic intra-tumor double primary metastases in the lung. This patient was a 40-year-old Korean woman who had been diagnosed with breast cancer (T1N0M0, estrogen receptor/progesterone receptor/HER2 +/+/+) and papillary thyroid cancer three years prior and underwent a complete surgical resection followed by appropriate adjuvant treatment with radiation, hormone, and radioactive iodine. She was recently admitted for newly developed pulmonary nodules. Metastasectomy through video-assisted thoracoscopic surgery revealed recurrent double primary cancer with two different components (metastatic ductal carcinomas from the breast and metastatic papillary carcinomas from the thyroid gland) in each pulmonary nodule in the right upper lobe and right middle lobe. To the best of our knowledge, this is the first report of simultaneous recurrent double metastasis in one organ from different primary origins.
doi:10.4143/crt.2014.46.2.200
PMCID: PMC4022830  PMID: 24851113
Double primary tumor; Neoplasm metastasis; Intra-tumoral heterogeneity
13.  Tumor Lysis Syndrome in a Patient with Metastatic Colon Cancer after Treatment with 5-Fluorouracil/Leucovorin and Oxaliplatin: Case Report and Literature Review 
Development of tumor lysis syndrome (TLS) may occur after chemotherapy or spontaneously in bulky or rapidly growing tumors. This syndrome is frequent but preventable in patients with hematologic malignancies. TLS following therapy has been reported infrequently in various types of solid tumors. TLS associated with oxaliplatin containing chemotherapy in a solid tumor has never been reported. A 59-year-old man received 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy for metastatic colon cancer. Development of TLS occurred three days after administration of chemotherapy. Two days later, his abnormal laboratory findings were recovered with appropriate management. To the best of our knowledge, the current case is the first report on development of acute TLS following oxaliplatin containing chemotherapy in a patient with colon cancer. We also review the literature on tumor lysis syndrome in patients with colorectal cancer.
doi:10.4143/crt.2014.46.2.204
PMCID: PMC4022831  PMID: 24851114
Tumor lysis syndrome; Oxaliplatin; Colon
15.  Primary Follicular Lymphoma in a Male Breast: A Case Report 
Primary breast lymphoma (PBL) is a rare disease, particularly in males. Diffuse large B cell lymphoma is the most common PBL, while follicular lymphoma is less common. Furthermore, primary follicular lymphoma of a male breast is rarely reported. We report a male patient with primary follicular lymphoma of the breast and hepatocellular carcinoma (HCC). A 46-year-old man was diagnosed with liver cirrhosis secondary to chronic hepatitis B infection. Ten years later, he underwent segmentectomy of the liver due to HCC. Another 5 months later, he presented with a painless mass in the right chest wall. The mass was diagnosed as follicular lymphoma of the breast. The stage was IEA and he did not receive adjuvant therapy. Although only a few cases have been reported, lymphoma should be considered as a possible cause of breast mass, even in male patients.
doi:10.4143/crt.2014.46.1.104
PMCID: PMC3918521  PMID: 24520230
Breast; Follicular lymphoma; Hepatocellular carcinoma; Liver cirrhosis; Male
16.  A Randomized Double-Blind, Double-Dummy, Multicenter Trial of Azasetron versus Ondansetron to Evaluate Efficacy and Safety in the Prevention of Delayed Nausea and Vomiting Induced by Chemotherapy 
Purpose
This study was conducted to evaluate the efficacy and safety of azasetron compared to ondansetron in the prevention of delayed chemotherapy-induced nausea and vomiting.
Materials and Methods
This study was a multi-center, prospective, randomized, double-dummy, double-blind and parallel-group trial involving 12 institutions in Korea between May 2005 and December 2005. A total of 265 patients with moderately and highly emetogenic chemotherapy were included and randomly assigned to either the azasetron or ondansetron group. All patients received azasetron (10 mg intravenously) and dexamethasone (20 mg intravenously) on day 1 and dexamethasone (4 mg orally every 12 hours) on days 2-4. The azasetron group received azasetron (10 mg orally) with placebo of ondansetron (orally every 12 hours), and the ondansetron group received ondansetron (8 mg orally every 12 hours) with placebo of azasetron (orally) on days 2-6.
Results
Over days 2-6, the effective ratio of complete response in the azasetron and ondansetron groups was 45% and 54.5%, respectively (95% confidence interval, -21.4 to 2.5%). Thus, the non-inferiority of azasetron compared with ondansetron in delayed chemotherapy-induced nausea and vomiting was not proven in the present study. All treatments were well tolerated and no unexpected drug-related adverse events were reported. The most common adverse events related to the treatment were constipation and hiccups, and there were no differences in the overall incidence of adverse events.
Conclusion
In the present study, azasetron showed inferiority in the control of delayed chemotherapy-induced nausea and vomiting compared with ondansetron whereas safety profiles were similar between the two groups.
doi:10.4143/crt.2014.46.1.19
PMCID: PMC3918522  PMID: 24520219
Vomiting; Vomiting/chemically induced; Vomiting/prevention and control; Antineoplastic agents; Serotonin antagonists; Azasetron; Ondansetron
17.  Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice 
Curcumin (diferuloylmethane) is a yellow pigment present in the spice turmeric (Curcuma longa) that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6,000 citations. In addition, over one hundred clinical studies have been carried out with curcumin. One of the major problems with curcumin is perceived to be the bioavailability. How curcumin should be delivered in vivo, how bioavailable is it, how well curcumin is absorbed and how it is metabolized, is the focus of this review. Various formulations of curcumin that are currently available are also discussed.
doi:10.4143/crt.2014.46.1.2
PMCID: PMC3918523  PMID: 24520218
Curcumin; Nano-formulation; Biological availability; Metabolism; Anticancer
18.  Chemotherapy in Advanced Gastric Cancer Patients Associated with Disseminated Intravascular Coagulation 
Purpose
Little is known about the clinical features of advanced gastric cancer (AGC) combined with disseminated intravascular coagulation (DIC). The main objective of this study was to determine the clinical outcome of patients with AGC complicated by DIC.
Materials and Methods
We conducted a retrospective review of 68 AGC patients diagnosed with DIC at four tertiary medical centers between January 1995 and June 2010.
Results
Sixty eight patients were included. The median age was 55 years (range, 25 to 78 years). Nineteen patients received chemotherapy, whereas 49 patients received only best supportive care (BSC). The median overall survival (OS) of the 68 patients was 16 days (95% confidence interval [CI], 11 to 21 days). Significantly prolonged OS was observed in the chemotherapy group, with a median survival of 61 days compared to 9 days in the BSC group (p<0.001, log-rank test). Age and previous chemotherapy were another significant factors that were associated with OS in univariate analysis. In multivariate analysis, age (≥65 vs. <65; hazard ratio [HR], 0.38; 95% CI, 0.18 to 0.78; p<0.001), chemotherapy (BSC vs. chemotherapy; HR 0.31; 95% CI, 0.15 to 0.63; p<0.001), and previous chemotherapy (yes or no; HR, 0.49; 95% CI, 0.25 to 0.98; p<0.045) were consistently independent prognostic factors that impacted OS.
Conclusion
Our study showed that patients with AGC complicated by DIC had very poor OS, and suggested that chemotherapy might improve OS of these patients.
doi:10.4143/crt.2014.46.1.27
PMCID: PMC3918524  PMID: 24520220
Stomach neoplasms; Disseminated intravascular coagulation; Drug therapy
19.  The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma 
Purpose
To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications.
Materials and Methods
Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received radiotherapy alone. Ten patients received chemotherapy before radiotherapy, and three patients underwent surgery followed by chemotherapy and radiotherapy. One patient received surgery followed by radiotherapy. All patients received radiotherapy of median dose of 30.6 Gy.
Results
The duration of follow-up ranged from 6 to 158 months (median, 48 months). Five-year overall survival and cause-specific survival rates were 90.3% and 100%. All patients treated with radiotherapy alone achieved pathologic complete remission (pCR) in 31 of the low-grade and in three of the mixed-grade patients. All patients treated with chemotherapy and/or surgery prior to radiotherapy achieved pCR except one patient who received chemotherapy before radiotherapy. During the follow-up period, three patients developed diffuse large B-cell lymphoma in the stomach, and one developed gastric adenocarcinoma after radiotherapy. No grade 3 or higher acute or late complications developed. One patient, who initially exhibited gastroptosis, developed mild atrophy of left kidney.
Conclusion
These findings indicate that a modest dose of radiotherapy alone can achieve a high cure rate for low-grade and even mixed-grade gastric MALT lymphoma without serious toxicity. Patients should be carefully observed after radiotherapy to screen for secondary malignancies.
doi:10.4143/crt.2014.46.1.33
PMCID: PMC3918525  PMID: 24520221
Stomach; Marginal zone B-cell lymphoma; Radiotherapy
20.  A Distribution Weighted Prognostic Scoring Model for Node Status in Advanced Rectal Cancer 
Purpose
There are various lymph node-based staging systems. Nevertheless, there is debate over the use of parameters such as the number of involved lymph nodes and the lymph node ratio. As a possible option, the distribution of metastatic lymph nodes may have a prognostic significance in rectal cancer. This study is designed to evaluate the impact of distribution-weighted nodal staging on oncologic outcome in rectal cancer.
Materials and Methods
From a prospectively maintained colorectal cancer database of our institution, a total of 435 patients who underwent a curative low anterior resection for mid and upper rectal cancer between 1995 and 2004 were enrolled. Patients were divided into 3 groups according to the location of apical metastatic nodes. A location-weighted prognostic score was calculated by a scoring model using a logistic regression test for location based-statistical weight to number of lymph nodes. All cases were categorized in quartiles from lymph node I to lymph node IV using this protocol.
Results
The location of lymph node metastasis was an independent factor that was associated with a poor prognostic outcome (p<0.001). Based on this result, the location-weighted-nodal prognostic scoring model did not show lesser significant results (p<0.0001) in both overall survival and cancer-free survival analyses.
Conclusion
The location of apical nodes among the metastatic nodes does not have a lesser significant impact on oncologic result in patients with advanced rectal cancer. A location-weighted prognostic scoring model, which considered the numbers of involved lymph nodes as the rate of significance according to the location, may more precisely predict the survival outcome in patients with lymph node metastasis.
doi:10.4143/crt.2014.46.1.41
PMCID: PMC3918526  PMID: 24520222
Rectal neoplasms; Prognostic scoring model; Lymph nodes; Neoplasm staging
21.  Dose KRAS Mutation Status Affect on the Effect of VEGF Therapy in Metastatic Colon Cancer Patients? 
Purpose
Mutations affecting the KRAS gene are an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, the role of KRAS mutation as a biomarker for anti-vascular endothelial growth factor (VEGF) remains controversial.
Materials and Methods
We analyzed retrospective data from 32 CRC patients who were available for KRAS mutation status and received cytotoxic chemotherapy plus bevacizumab as a first-line therapy. Six of 32 patients received anti-EGFR therapies. We used KRAS mutation status as a predictive or prognostic factor in CRC patients receiving bevacizumab.
Results
We observed mutations in KRAS in 59.4% of patients. Bevacizumab was used in combination with oxaliplatin based regimens. There was no significant difference for progression free survival (PFS) and overall survival (OS) in patients with oxaliplatin based cytotoxic chemotherapy plus bevacizumab according to the status of KRAS mutation. After first-line therapy, 28 patients (87.5%) received second-line therapy. In univariate analysis, KRAS mutations did not have a major prognostic value for PFS (hazard ratio, 1.007; 95% confidence interval [CI], 0.469 to 2.162; p>0.05) or OS (hazard ratio, 0.548; 95% CI, 0.226 to 1.328; p>0.05). In addition, anti-EGFR therapies did not affect the impact on OS.
Conclusion
KRAS mutation is neither a predictive for bevacizumab nor a prognostic for OS in CRC patients receiving anti-VEGF therapy.
doi:10.4143/crt.2014.46.1.48
PMCID: PMC3918527  PMID: 24520223
KRAS; Vascular endothelial growth factor; Colonic neoplasms
22.  Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil 
Purpose
The novel heat shock protein tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells in vitro. Excision repair cross-complementation group 1 (ERCC1) expression levels in tumor tissues also predict clinical outcomes in metastatic CRC patients receiving combination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1 and ERCC1 protein expression by immunohistochemistry predict clinical outcomes in CRC patients.
Materials and Methods
The study population consisted of 56 patients with metastatic CRC who received first-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS) by levels of the markers TRAP1 and ERCC1 were evaluated.
Results
The rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patients negative for ERCC1 expression showed a tendency to respond to chemotherapy (p=0.066). Median OS was significantly longer in patients negative for TRAP1 than those positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also had a better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9 months for patients negative for TRAP1 and ERCC1 compared to 13.2 months for those positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). The combination of TRAP1 and ERCC1 expression was significantly associated with the response to chemotherapy (p=0.046) and independently predicted median OS in multivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49).
Conclusion
The present study demonstrates that the combination of TRAP1 and ERCC1 expression predicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.
doi:10.4143/crt.2014.46.1.55
PMCID: PMC3918528  PMID: 24520224
Colorectal neoplasms; ERCC1; Fluorouracil; Oxaliplatin; TRAP1
23.  Clinical Implications of Systemic Inflammatory Response Markers as Independent Prognostic Factors in Colorectal Cancer Patients 
Purpose
Cancer-related inflammation affects many aspects of malignancy. We confirm the effects of early postoperative systemic inflammation on cancer prognosis.
Materials and Methods
Six hundred consecutive patients underwent surgery for colorectal cancer from 2006 to 2009. Measurements of white blood cells, neutrophils, lymphocytes, monocytes, and platelet counts were performed preoperatively, daily until the fourth postoperative day, and subsequently every two days. Patients were divided into three groups based on the days spent on the leukocyte count to drop below 10,000/mm3 after surgery.
Results
Preoperative white blood cell (WBC) counts correlated with stage of disease. In univariate survival analyses, tumor, node, metastasis (TNM) stage, and monocyte count were associated with cancer-free survival. In addition, cancer-free survival outcomes were worse in patients who required more than four days for the normalization of WBC count. A TNM stage greater than II and the neutrophil lymphocyte ratio were associated with the duration of overall survival. In a multivariate analysis of these significant variables, TNM stage, an interval longer than four days for normalization of WBC counts and monocyte count independently associated with cancer-free survival.
Conclusion
Postoperative early inflammatory phase and preoperative monocyte count correlate with poor colon cancer prognosis. We can conclude that preoperative and postoperative inflammatory response and period unfavorably affect the metastatic microenvironment.
doi:10.4143/crt.2014.46.1.65
PMCID: PMC3918529  PMID: 24520225
Colorectal neoplasms; Inflammation; Perioperative period; Prognosis
24.  High-Dose-Rate Brachytherapy for the Treatment of Vaginal Intraepithelial Neoplasia 
Purpose
Vaginal intraepithelial neoplasia (VAIN), a rare premalignant condition, is difficult to eradicate. We assess the effectiveness of high-dose rate intracavitary brachytherapy (HDR-ICR) in patients with VAIN or carcinoma in situ (CIS) of the vagina after hysterectomy.
Materials and Methods
We reviewed 34 patients treated for posthysterectomy VAIN or CIS of the vagina by brachytherapy as the sole treatment. All patients underwent a coloposcopic-directed punch biopsy or had abnormal cytology, at least 3 consecutive times. All patients were treated with a vaginal cylinder applicator. The total radiation dose was mainly 40 Gy in 8 fractions during the periods of 4 weeks at a prescription point of the median 0.2 cm (range, 0 to 0.5 cm) depth from the surface of the vaginal mucosa.
Results
Acute toxicity was minimal. Seven patients had grade 1/2 acute urinary and rectal complications. There were 15 cases of late toxicity, predominantly vaginal mucosal reaction in 12 patients. Of these patients, two patients suffered from grade 3 vaginal stricture and dyspareunia continuously. After a median follow-up time of 48 months (range, 4 to 122 months), there were 2 recurrences and 2 persistent diseases, in which a second-line therapy was needed. The success rate was 88.2%. The average prescription point in failure patients was 1.1 mm from the surface of the vagina compared to an average of 2.6 mm in non-recurrent patients (p=0.097).
Conclusion
HDR-ICR is an effective treatment method in VAIN patients. In spite of high cure rates, we should consider issues regarding vaginal toxicity and radiation techniques to reduce the occurrence of failure and toxicity.
doi:10.4143/crt.2014.46.1.74
PMCID: PMC3918530  PMID: 24520226
Vaginal neoplasms; Carcinoma in situ; Radiotherapy; Brachytherapy
25.  Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3 
Purpose
Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis.
Materials and Methods
OVCAR-3 cells were exposed to paclitaxel (20 µM) in the absence or presence of celecoxib (10 µM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosis was evaluated using Annexin-V/7-aminoactinomycin D staining and a cellular DNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavage of poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF) and Akt activation were assessed using reverse transcriptase-polymerase chain reaction and western blotting.
Results
Celecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxib significantly increased paclitaxel-induced apoptosis of OVCAR-3 cells. Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination with paclitaxel resulted in downregulation of NF-κB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt.
Conclusion
OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-κB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may prove beneficial in the clinical treatment of ovarian cancer.
doi:10.4143/crt.2014.46.1.81
PMCID: PMC3918531  PMID: 24520227
Ovarian neoplasms; Celecoxib; Paclitaxel; Apoptosis; NF-kappa B; Akt

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