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1.  Prognostic significance of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in biliary tract cancer patients receiving adjuvant 5-fluorouracil-based chemotherapy 
Molecular and Clinical Oncology  2013;1(6):987-994.
Biliary tract cancer (BTC) is a relatively uncommon type of cancer, accounting for ∼4% of the malignant neoplasms of the gastrointestinal tract. The aim of this study was to determine whether the expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) predict clinical outcome in BTC patients treated with adjuvant 5-fluorouracil (5-FU)-based chemotherapy. TS and TP expression were found to be significantly correlated with cancer location (P=0.044 and 0.031, respectively). The multivariate analysis revealed that age [hazard ratio (HR)=2.157, P=0.008], stage (HR=2.234, P<0.001), resection margin status (HR=2.748, P=0.004) and TP expression (HR=2.014, P=0.039) were independently associated with overall survival (OS).
doi:10.3892/mco.2013.166
PMCID: PMC3915652  PMID: 24649282
biliary tract cancer; 5-fluorouracil; thymidine phosphorylase
2.  Redescription of two Pennellids (Copepoda, Siphonostomatoida) from Korea with a key to species of Peniculus von Nordmann, 1832  
ZooKeys  2012;1-14.
Redescriptions of two pennellid copepods, Peniculus minuticaudae Shiino, 1956 and Peniculus truncatus Shiino, 1956, are provided, based on postmetamorphic adult females collected from marine ranched fishes captured at Tongyeong marine living resources research & conservation center, Korea. Peniculus minuticaudae was collected from the soft fin rays of black scraper Thamnaconus modestus. It can be distinguished from the other two closely related congeners Peniculus ostraciontis Yamaguti, 1939 and Peniculus truncatus by having a well developed triangular-shaped abdomen; the abdomen is rudimentary in other two species. This is thefirst report of the occurrence of Peniculus minuticaudae in Korea. Peniculus truncatus was collected from the dorsal fin of Korean rockfish Sebastes schlegelii. It can be distinguished from Peniculus minuticaudae by the combination of a rudimentary abdomen, long neck and setae on leg 1 and from Peniculus ostraciontis by the long neck, slender trunk, and setae on leg 1. It is also shown that Peniculus truncatus captured from the same host in Korea was misidentified as Peniculus ostraciontis and hence, this is thesecond record of the occurrence of Peniculus truncatus in Korea. A key is provided for the 14 nominal species of Peniculus.
doi:10.3897/zookeys.243.3668
PMCID: PMC3552349  PMID: 23372416
Copepod; pennellid; parasite; redescription; black scraper; rockfish; fins; identification; key
3.  Clinicopathologic significance of expression of nuclear factor-κB RelA and its target gene products in gastric cancer patients 
AIM: To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer.
METHODS: The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry.
RESULTS: Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.
CONCLUSION: Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.
doi:10.3748/wjg.v18.i34.4744
PMCID: PMC3442213  PMID: 23002344
Nuclear factor-κB; Vascular endothelial growth factor; Interleukin-6; C-reactive protein; Serum amyloid A; Stomach; Carcinoma
4.  Bevacizumab as a second- or later-line of treatment for metastatic colorectal cancer 
AIM: To determine the efficacy of bevacizumab in patients with metastatic colorectal cancer (MCRC) who have failed prior chemotherapy without bevacizumab.
METHODS: Between March 2002 and June 2010, 40 patients in South Korea with MCRC who were treated with bevacizumab plus chemotherapy as a second or later-line treatment were analyzed retrospectively for their overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS: All of the patients had progressed under prior chemotherapy without bevacizumab. Three patients (7.5%) exhibited an ORR, twenty one patients (52.5%) exhibited stable disease (SD), and fifteen patients (37.5%) exhibited disease progression. The median duration of the OS and PFS were 14.0 mo and 6.13 mo respectively. The median OSs were 16.60, 14.07 and 13.00 mo for second-line, third-line and fourth- or later-line treatments, respectively. The median PFSs were 7.23, 7.30 and 3.87 mo for the second-line, third-line and fourth- or later-line treatments, respectively.
CONCLUSION: In patients with MCRC, bevacizumab combined chemotherapy may be beneficial during second- or later-line treatment.
doi:10.3748/wjg.v18.i10.1104
PMCID: PMC3296985  PMID: 22416186
Colorectal cancer; Metastasis; Bevacizumab; Efficacy; Second- or later-line
5.  Gastric leptomeningeal carcinomatosis: Multi-center retrospective analysis of 54 cases 
AIM: To identify the clinical features and outcomes of infrequently reported leptomeningeal carcinomatosis (LMC) of gastric cancer.
METHODS: We analyzed 54 cases of cytologically confirmed gastric LMC at four institutions from 1994 to 2007.
RESULTS: The male-to-female ratio was 32:22, and the patients ranged in age from 28 to 78 years (median, 48.5 years). The majority of patients had advanced disease at initial diagnosis of gastric cancer. The clinical or pathologic tumor, node and metastasis stage of the primary gastric cancer was IV in 38 patients (70%). The median interval from diagnosis of the primary malignancy to the diagnosis of LMC was 6.3 mo, ranging between 0 and 73.1 mo. Of the initial endoscopic findings for the 45 available patients, 23 (51%) of the patients were Bormann type III and 15 (33%) patients were Bormann type IV. Pathologically, 94% of cases proved to be poorly differentiated adenocarcinomas. Signet ring cell component was also observed in 40% of patients. Headache (85%) and nausea/vomiting (58%) were the most common presenting symptoms of LMC. A gadolinium-enhanced magnetic resonance imaging was conducted in 51 patients. Leptomeningeal enhancement was noted in 45 cases (82%). Intrathecal (IT) chemotherapy was administered to 36 patients-primarily methotrexate alone (61%), but also in combination with hydrocortisone/± Ara-C (39%). The median number of IT treatments was 7 (range, 1-18). Concomitant radiotherapy was administered to 18 patients, and concomitant chemotherapy to seven patients. Seventeen patients (46%) achieved cytological negative conversion. Median overall survival duration from the diagnosis of LMC was 6.7 wk (95% CI: 4.3-9.1 wk). In the univariate analysis of survival duration, hemoglobin, IT chemotherapy, and cytological negative conversion showed superior survival duration (P = 0.038, P = 0.010, and P = 0.002, respectively). However, in our multivariate analysis, only cytological negative conversion was predictive of relatively longer survival duration (3.6, 6.7 and 14.6 wk, P = 0.030, RR: 0.415, 95% CI: 0.188-0.918).
CONCLUSION: Although these patients had a fatal clinical course, cytologic negative conversion by IT chemotherapy may improve survival.
doi:10.3748/wjg.15.5086
PMCID: PMC2768889  PMID: 19860003
Carcinomatosis; Gastric cancer; Intrathecal chemotherapy; Leptomeningeal
6.  Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy: A pilot study 
AIM: To evaluate the combination of bevacizumab with infusional 5-fluorouracil (5-FU), leucovorin (LV) and irinotecan (FOLFIRI) in patients with advanced colorectal cancer (CRC) pretreated with combination regimens including irinotecan and oxaliplatin.
METHODS: Fourteen patients (median age 56 years) with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d.
RESULTS: The median number of cycles of chemotherapy was six (range 3-12). The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo (95% CI 2.0-8.7), and the median overall survival was 10.9 mo (95% CI 9.6-12.1). Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles.
CONCLUSION: Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.
doi:10.3748/wjg.v13.i46.6231
PMCID: PMC4171235  PMID: 18069765
Bevacizumab; Irinotecan; Leucovorin; 5-fluorouracil; Colorectal cancer
7.  Treatment of Dexamethasone-Induced Hiccup in Chemotherapy Patients by Methylprednisolone Rotation 
The Oncologist  2013;18(11):1229-1234.
Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in patients with cancer, and little information is available about its treatment. The aims of this study were to investigate the feasibility of methylprednisolone rotation as treatment and to confirm the male predominance among those with cancer who experienced DIH during chemotherapy. DIH during chemotherapy could be controlled without losing antiemetic potential by replacing dexamethasone with methylprednisolone.
Background.
Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in patients with cancer, and little information is available about its treatment. The aims of this study were to investigate the feasibility of methylprednisolone rotation as treatment and to confirm the male predominance among those with cancer who experienced DIH during chemotherapy.
Methods.
Persons with cancer who experienced hiccups during chemotherapy treatment and who were receiving treatment with dexamethasone were presumed to have DIH. The following algorithmic practice was implemented for antiemetic corticosteroid use: rotation from dexamethasone to methylprednisolone in the next cycle and dexamethasone re-administration in the second cycle of chemotherapy after recognition of hiccups to confirm DIH. All other antiemetics except corticosteroid remained unchanged. Patients (n = 40) were recruited from eight cancer centers in Korea from September 2012 to April 2013. Data were collected retrospectively.
Results.
Hiccup intensity (numeric rating scale [NRS]: 5.38 vs. 0.53) and duration (68.44 minutes vs. 1.79 minutes) were significantly decreased after rotation to methylprednisolone, while intensity of emesis was not increased (NRS: 2.63 vs. 2.08). Median dose of dexamethasone and methylprednisolone were 10 mg and 50 mg, respectively. Thirty-four (85%) of 40 patients showed complete resolution of hiccups after methylprednisolone rotation in the next cycle. Of these 34 patients, 25 (73.5%) had recurrence of hiccups after dexamethasone re-administration. Compared with baseline values, hiccup intensity (NRS: 5.24 vs. 2.44) and duration (66.43 minutes vs. 22.00 minutes) were significantly attenuated after dexamethasone re-administration. Of the 40 eligible patients, 38 (95%) were male.
Conclusion.
DIH during chemotherapy could be controlled without losing antiemetic potential by replacing dexamethasone with methylprednisolone. We also identified a male predominance of DIH. Further prospective studies are warranted.
doi:10.1634/theoncologist.2013-0224
PMCID: PMC3825309  PMID: 24107973
Dexamethasone; Hiccup; Methylprednisolone; Corticosteroids
8.  Clinical Usefulness of Hydromorphone-OROS in Improving Sleep Disturbances in Korean Cancer Patients: A Multicenter, Prospective, Open-Label Study 
Purpose
To evaluate the efficacy of hydromorphone-OROS (HM-OROS) in reducing sleep disturbance and relieving cancer pain.
Materials and Methods
One hundred twenty cancer patients with pain (numeric rating scale [NRS] ≥ 4) and sleep disturbance (NRS ≥ 4) were evaluated. The initial HM-OROS dosing was based on previous opioid dose (HM-OROS:oral morphine=1:5). Dose adjustment of the study drug was permitted at the investigator’s discretion. Pain intensity, number of breakthrough pain episodes, and quality of sleep were evaluated.
Results
A total of 120 patients received at least one dose of HM-OROS; 74 of them completed the final assessment. Compared to the previous opioids, HM-OROS reduced the average pain NRS from 5.3 to 4.1 (p < 0.01), worst pain NRS from 6.7 to 5.4 (p < 0.01), sleep disturbance NRS from 5.9 to 4.1 (p < 0.01), incidence of breakthrough pain at night from 2.63 to 1.53 times (p < 0.001), and immediate-release opioids use for the management of breakthrough pain from 0.83 to 0.39 times per night (p = 0.001). Of the 74 patients who completed the treatment, 83.7% indicated that they preferred HM-OROS to the previous medication. The adverse events (AEs) were somnolence, asthenia, constipation, dizziness, and nausea.
Conclusion
HM-OROS was efficacious in reducing cancer pain and associated sleep disturbances. The AEs were manageable.
doi:10.4143/crt.2013.130
PMCID: PMC4206066  PMID: 25043822
Cancer pain; Sleep disturbance; Hydromorphone-OROS (HM-OROS)
9.  Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report 
Purpose
Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient’s part can cause major obstacles in pain management.
Method
We evaluated factors associated with patient’s high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory—Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed.
Results
The patients were from nine oncology clinics in university hospitals and a veterans’ hospital in South Korea. The median pain score (0–10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale.
Conclusions
Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.
doi:10.1007/s00520-012-1646-x
PMCID: PMC3881357  PMID: 23151648
Cancer; Depression; Pain management
10.  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
11.  Long-Term Survival Analysis and Clinical Follow-Up in Acral Lentiginous Malignant Melanoma Undergoing Sentinel Lymph Node Biopsy in Korean Patients 
Annals of Dermatology  2014;26(2):177-183.
Background
In cutaneous malignant melanoma (MM) with clinically uninvolved regional lymph nodes, sentinel lymph node (SLN) status is the most powerful indicator of both overall survival (OS) and disease-free survival (DFS). However, no studies on the long-term survival and clinical follow-up of Korean patients with acral lentiginous MM (ALM) undergoing SLN biopsy (SLNB) have been published.
Objective
The purpose of this study was to investigate the clinical prognosis and long-term survival of Korean patients with ALM according to SLN status.
Methods
Thirty-four ALM patients undergoing SLNB were included in this study. We evaluated clinical and histopathological follow-up data such as the stage of disease, treatment, recurrence, and metastasis, and analyzed OS and DFS according to SLN status.
Results
The median follow-up time was 60.5 months (range 3~127 months). Positive SLNs were noted in 14 patients (41.2%). Patients with negative SLNs had better OS and DFS than those with positive SLNs (p<0.05). Increased Breslow thickness was associated with short OS and DFS (p<0.05), and female patients showed better DFS than male patients (p<0.05).
Conclusion
To our knowledge, this is the first study on the long-term survival and clinical follow-up of patients undergoing SLNB for ALM in Korea. Our findings show that SLN status is an important prognostic factor for predicting OS and DFS.
doi:10.5021/ad.2014.26.2.177
PMCID: PMC4037669  PMID: 24882971
Acral lentiginous malignant melanoma; Prognosis; Sentinel lymph node biopsy; Survival
12.  Clinical features and treatment outcomes in patients with mantle cell lymphoma in Korea: Study by the Consortium for Improving Survival of Lymphoma 
Blood research  2014;49(1):15-21.
Background
We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea.
Methods
We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL.
Results
The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS.
Conclusion
Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.
doi:10.5045/br.2014.49.1.15
PMCID: PMC3974951  PMID: 24724062
Mantle cell lymphoma; Epidemiology; Trend; Survival; Chemotherapy; Rituximab
13.  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
14.  Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy 
BMC Cancer  2013;13:350.
Background
Several inflammatory response materials could be used for prediction of prognosis of cancer patients. The neutrophil lymphocyte ratio (NLR), and the platelet lymphocyte ratio (PLR) have been introduced for prognostic scoring system in various cancers. The objective of this study was to determine whether the NLR or the PLR would predict the clinical outcomes in advanced gastric cancer patients treated with oxaliplatin/ 5-fluorouracil (FOLFOX).
Methods
The study population consisted of 174 advanced gastric cancer patients. Patients were treated with 85 mg/m2 of oxaliplatin as a 2-h infusion at day 1 plus 20 mg/m2 of leucovorin over 10 min, followed by 5-FU bolus 400 mg/m2 and 22-h continuous infusion of 600 mg/m2 at days 1-2. Treatment was repeated in 2-week intervals. The NLR and PLR were calculated from complete blood counts in laboratory test before and after first cycle of chemotherapy.
Results
NLR was a useful prognostic biomarker for predicting inferior overall survival (OS) (p = 0.005), but was not associated with progression free survival (PFS) (p = 0.461). The normalization of NLR after one cycle of chemotherapy was found to be in association with significant improvement in PFS (5.3 months vs. 2.4 months, p < 0.001), and OS (11.9 months vs. 4.6 months, p < 0.001). The normalization of PLR was also associated with longer PFS (5.6 months vs. 3.4 months, p = 0.006), and OS (16.9 months vs. 10.9 months, p = 0.002). In multivariate analysis, changes in NLR were associated with PFS (Hazard ratio (HR): 2.297, 95% confidence interval (CI): 1.429-3.693, p = 0.001). The NLR, (HR: 0.245, 95% CI: 0.092-0.633, p = 0.004), PLR (HR: 0.347, 95% CI: 0.142-0.847, p = 0.020), changes in NLR (HR: 2.468, 95% CI: 1.567-3.886, p < 0.001), and changes in PLR (HR: 1.473, 95% CI: 1.038-2.090, p = 0.030) were independent prognostic markers for OS.
Conclusion
This study demonstrates that NLR, PLR, and changes in NLR or PLR are independent prognostic factor for OS in patients with advanced gastric cancer treated with chemotherapy. These specific factors may also help in identifying the patients, who are more sensitive to FOLFOX regimen.
doi:10.1186/1471-2407-13-350
PMCID: PMC3729814  PMID: 23876227
Neutrophil; Lymphocyte; Platelet; Gastric neoplasm
15.  Third-line docetaxel chemotherapy for recurrent and metastatic gastric cancer 
Background/Aims
To determine the efficacy and toxicity of docetaxel as a third-line therapy for patients with relapsed gastric cancer who have undergone modified oxaliplatin-fluorouracil (m-FOLFOX)-4 and modified irinotecan-fluorouracil (m-FOLFIRI) regimens.
Methods
We analyzed 33 patients who had been histologically diagnosed with adenocarcinoma of the stomach and who had progressed after m-FOLFOX-4 and m-FOLFIRI regimens. Patients were treated with cycles of 75 mg/m2 docetaxel on day 1 every 3 weeks.
Results
The median age of the patients was 56.0 years (range, 31.0 to 74.0), and 73% of the patients (24/33) had an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients were evaluated in terms of tumor response: five (15%), nine (27%), and 19 (58%) patients experienced a partial response, stable disease, and progressive disease, respectively. The median time to progression was 2.1 months (95% confidence interval [CI], 1.63 to 2.58), and overall survival was 4.7 months (95% CI, 3.20 to 6.20), from the start of the docetaxel regimen. Assessing patients' toxicity profiles, the median number of cycles was 2.0 (range, 1.0 to 12.0). The major hematologic toxicities included grade 3 to 4 neutropenia (19/33, 58%), grade 3 to 4 thrombocytopenia (2/33, 6%), and grade 3 to 4 anemia (5/33, 15%). Neutropenic fever developed in three patients (3/33, 9%). The nonhematological toxicities were nausea and vomiting (10/33, 30%), abdominal pain (4/33, 12%), skin rash (1/33, 3%), and fluid retention (3/33, 9%).
Conclusions
Docetaxel is a feasible third-line therapy regimen for patients with advanced gastric cancer after m-FOLFIRI and m-FOLFOX-4 regimens.
doi:10.3904/kjim.2013.28.3.314
PMCID: PMC3654129  PMID: 23682225
Advanced gastric cancer; Docetaxel; Salvage therapy
16.  The relationship of Vascular endothelial growth factor gene polymorphisms and clinical outcome in advanced gastric cancer patients treated with FOLFOX: VEGF polymorphism in gastric cancer 
BMC Cancer  2013;13:43.
Background
The aim of this study is to evaluate the associations between vascular endothelial growth factor (VEGF) Single-nucleotide polymorphisms (SNPs) and clinical outcome in advanced gastric cancer patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX).
Methods
Genomic DNA was isolated from whole blood, and six VEGF (−2578C/A, -2489C/T, -1498 T/C, -634 G/C, +936C/T, and +1612 G/A) gene polymorphisms were analyzed by PCR. Levels of serum VEGF were measured using enzyme-linked immunoassays.
Results
Patients with G/G genotype for VEGF -634 G/C gene polymorphism showed a lower response rate (22.2%) than those with G/C or C/C genotype (32.3%, 51.1%; P = 0.034). Patients with the VEGF -634 G/C polymorphism G/C + C/C genotype had a longer progression free survival (PFS) of 4.9 months, compared with the PFS of 3.5 months for those with the G/G (P = 0.043, log-rank test). By multivariate analysis, this G/G genotype of VEGF -634 G/C polymorphism was identified as an independent prognostic factor (Hazard ratio 1.497, P = 0.017).
Conclusion
Our data suggest that G/G genotype of VEGF -634 G/C polymorphism is related to the higher serum levels of VEGF, and poor clinical outcome in advanced gastric cancer patients.
doi:10.1186/1471-2407-13-43
PMCID: PMC3573956  PMID: 23374220
VEGF; Polymorphism; Gastric cancer
17.  The caligid life cycle: new evidence from Lepeophtheirus elegans reconciles the cycles of Caligus and Lepeophtheirus (Copepoda: Caligidae) 
Parasite  2013;20:15.
The developmental stages of the sea louse Lepeophtheirus elegans (Copepoda: Caligidae) are described from material collected from marine ranched Korean rockfish, Sebastes schlegelii. In L. elegans, setal number on the proximal segment of the antennule increases from 3 in the copepodid to 27 in the adult. Using the number of setae as a stage marker supports the inference that the post-naupliar phase of the life cycle comprises six stages: copepodid, chalimus I, chalimus II, pre-adult I, pre-adult II, and the adult. We observed variation in body length in both of the chalimus stages which we consider represents an early expression of sexual size dimorphism. We interpret the larger specimens of chalimus I as putative females, and the smaller as putative males; similarly with chalimus II, larger specimens are putative females and the smaller are males. Two patterns of life cycle are currently recognized within the Caligidae but the evidence presented here reconciles the two. We conclude that the typical caligid life cycle comprises only eight stages: two naupliar, one copepodid, and four chalimus stages preceding the adult in Caligus, but with the four chalimus stages represented by two chalimus and two pre-adult stages in Lepeophtheirus. This is a profound change with significant implications for the aquaculture industry, given that lice monitoring protocols include counts of chalimus stages and use temperature to predict when they will moult into the more pathogenic, mobile pre-adults. Lice management strategies must be tailored to the precise life cycle of the parasite.
doi:10.1051/parasite/2013015
PMCID: PMC3718518  PMID: 23647664
Caligidae; Copepoda; sea louse; life cycle; larval stages; developmental stages
18.  Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome 
The Korean Journal of Hematology  2012;47(3):186-193.
Background
Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD).
Methods
Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD.
Results
Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB.
Conclusion
DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.
doi:10.5045/kjh.2012.47.3.186
PMCID: PMC3464335  PMID: 23071473
Myelodysplastic syndrome; DNA methylation; GSTM5; ANGPTL2; BIK
19.  Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL) 
Background
The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.
Methods
Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.
Results
Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).
Conclusions
Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.
doi:10.1186/1756-8722-5-49
PMCID: PMC3445827  PMID: 22889180
Primary adrenal lymphoma; Diffuse large B-cell lymphoma; Prognostic factor; R-CHOP
20.  A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis 
Purpose
Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is common and is the second most common cause of death. Clinical studies regarding chemotherapy for CRC with PC have been classically rather limited in scope. We evaluated the efficacy of modified oxaliplatin, leucovorin, and fluorouracil (m-FOLFOX4) regimen for PC of CRC origin.
Materials and Methods
CRC patients with PC were treated with cycles of oxaliplatin at 85 mg/m2 on day 1, leucovorin 20 mg/m2 followed by 5-fluorouracil (5-FU) via a 400 mg/m2 bolus and a 22 hours continuous infusion of 600 mg/m2 5-FU on days 1-2 at 2-week intervals.
Results
Forty patients participated in this study. Median age was 55 years. Thirty-two patients (80.0%) received previous operation, and 60.0% of PC occurred synchronously. Thirty-five patients (87.5%) were assessable and exhibited measurable lesions. Two patients (5.7%) demonstrated complete response and five patients (14.3%) showed partial response. The median time to progression was 4.4 months (95% confidence interval, 2.5 to 6.3 months), the median overall survival time was 21.5 months (95% confidence interval, 17.2 to 25.7 months). There was no treatment related death. Presence of liver metastasis (p=0.022), performance status (p=0.039), and carcinoembryonic antigen level (p=0.016) were related to the time to progression. Patients with low carcinoembryonic antigen level (37.2 months vs. 15.6 months, p=0.001) or good performance status (22.5 months vs. 6.8 months, p=0.040) showed better overall survival.
Conclusion
The m-FOLFOX4 regimen was determined to be effective for CRC patients with PC.
doi:10.4143/crt.2011.43.4.225
PMCID: PMC3253864  PMID: 22247707
Colorectal neoplasms; Peritoneum; Carcinoma; Drug therapy
21.  Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL) 
BMC Cancer  2011;11:321.
Background
Primary intestinal non-Hodgkin lymphoma (NHL) is a heterogeneous disease with regard to anatomic and histologic distribution. Thus, analyses focusing on primary intestinal NHL with large number of patients are warranted.
Methods
We retrospectively analyzed 581 patients from 16 hospitals in Korea for primary intestinal NHL in this retrospective analysis. We compared clinical features and treatment outcomes according to the anatomic site of involvement and histologic subtypes.
Results
B-cell lymphoma (n = 504, 86.7%) was more frequent than T-cell lymphoma (n = 77, 13.3%). Diffuse large B-cell lymphoma (DLBCL) was the most common subtype (n = 386, 66.4%), and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) was the second most common subtype (n = 61, 10.5%). B-cell lymphoma mainly presented as localized disease (Lugano stage I/II) while T-cell lymphomas involved multiple intestinal sites. Thus, T-cell lymphoma had more unfavourable characteristics such as advanced stage at diagnosis, and the 5-year overall survival (OS) rate was significantly lower than B-cell lymphoma (28% versus 71%, P < 0.001). B symptoms were relatively uncommon (20.7%), and bone marrow invasion was a rare event (7.4%). The ileocecal region was the most commonly involved site (39.8%), followed by the small (27.9%) and large intestines (21.5%). Patients underwent surgery showed better OS than patients did not (5-year OS rate 77% versus 57%, P < 0.001). However, this beneficial effect of surgery was only statistically significant in patients with B-cell lymphomas (P < 0.001) not in T-cell lymphomas (P = 0.460). The comparison of survival based on the anatomic site of involvement showed that ileocecal regions had a better 5-year overall survival rate (72%) than other sites in consistent with that ileocecal region had higher proportion of patients with DLBCL who underwent surgery. Age > 60 years, performance status ≥ 2, elevated serum lactate dehydrogenase, Lugano stage IV, presence of B symptoms, and T-cell phenotype were independent prognostic factors for survival.
Conclusions
The survival of patients with ileocecal region involvement was better than that of patients with involvement at other sites, which might be related to histologic distribution, the proportion of tumor stage, and need for surgical resection.
doi:10.1186/1471-2407-11-321
PMCID: PMC3160411  PMID: 21798075
intestine; non-Hodgkin lymphoma; prognosis; histopathology
22.  Predictive Value of In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay in Advanced Gastric Cancer Patients Who Received Oral 5-Fluorouracil after Curative Resection 
Purpose
To assess the usefulness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) results in advanced gastric cancer patients receiving adjuvant chemotherapy.
Materials and Methods
Sixty-two patients underwent curative surgical resection between January, 2006 and December, 2008. Their highly purified surgical specimens were evaluated by ATP-CRAs. Of the 62, 49 had successful assay results and they received either oral 5-fluorouracil or other chemotherapies. We retrospectively analyzed data for 24 patients who were treated with oral 5-fluorouracil and whose assays were successful.
Results
The median observation time was 24.6 months (range, 10.1 to 40.9 months). The median treatment time was 11.2 months (range, 1.2 to 17.7 months). The median age was 66 years (range, 30 to 81 years). Patients were grouped into sensitive- and resistant-groups according to adenosine triphosphate-based chemotherapy response results for fluorouracil. The sensitive-group showed a significantly longer time to relapse (not reached in the sensitive-group vs. 24.8 months in the resistant-group, p=0.043) and longer overall survival compared to the resistant-group (not reached in the sensitive-group vs. 35.7 months in the resistant-group, p=0.16, statistically insignificant).
Conclusion
Patients who receive curative surgical resection significantly benefit from sensitive adjuvant chemotherapy according to ATP-CRA results for time to relapse.
doi:10.4143/crt.2011.43.2.117
PMCID: PMC3138915  PMID: 21811428
Adenosine triphosphate; Chemotherapy response assay; Gastric cancer; Fluorouracil; Adjuvant chemotherapy
23.  Phase II Study of Vinorelbine Plus Trastuzumab in HER2 Overexpressing Metastatic Breast Cancer Pretreated with Anthracyclines and Taxanes 
Journal of Breast Cancer  2011;14(2):140-146.
Purpose
The role of first-line trastuzumab-based therapy has been firmly established in patients with human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer. In this trial, we evaluated the efficacy and safety of a vinorelbine and trastuzumab combination chemotherapy in patients who were pretreated with anthracyclines and taxanes.
Methods
Thirty-three patients with HER2 overexpressing metastatic breast cancer, all of whom had previously been treated with anthracyclines and taxanes, were included in this study. The patients were treated with 25 mg/m2 of vinorelbine (over a 15-minute infusion) on days 1 and 8 every 3 weeks. Additionally, trastuzumab was administered at an initial dose of 4 mg/kg over 90 minutes, and was subsequently administered at weekly doses of 2 mg/kg (over 30 minutes).
Results
The median age of the patients was 53 years (range, 39-72 years). The overall response rate was 30.3% (10 patients; 95% confidence interval [CI], 23-57%). The median time to progression was 6.8 months (95% CI, 5.3-8.2 months). The median overall survival was 12.4 months (95% CI, 10.3-14.6 months). In the 194 cycles of treatment, the incidence rates of grade ≥3 neutropenia and anemia were 7.2% and 1.0%, respectively. Neutropenic fever was detected in three cycles (1.5%). The non-hematological toxicities were not severe: grade 1 or 2 nausea or vomiting was detected in 15.2%, and grade 2 neuropathy was noted in 6.1% of patients. None of the patients experienced any serious cardiac toxicity, and no treatment-related deaths occurred.
Conclusion
These results show that a combination chemotherapy consisting of vinorelbine and trastuzumab is useful in patients with HER2-overexpressing metastatic breast cancer who were pretreated with anthracyclines and taxanes, with a favorable toxicity profile.
doi:10.4048/jbc.2011.14.2.140
PMCID: PMC3148545  PMID: 21847410
Breast neoplasms; Metastasis; Trastuzumab; Vinorelbine
24.  Lessons learned from 100 initial cases of laparoscopic liver surgery 
Purpose
Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period.
Methods
This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures.
Results
The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%.
Conclusion
This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection.
doi:10.4174/jkss.2011.80.5.334
PMCID: PMC3204701  PMID: 22066057
Laparoscopic liver resection; Hepatic cyst; Hapatocellular carcinoma; Resection margin
25.  Incidence and clinical characteristics of clonal cytogenetic abnormalities of acquired aplastic anemia in adults 
The Korean Journal of Hematology  2010;45(4):242-246.
Background
Cytogenetic abnormalities (CAs) have been reported frequently in patients with otherwise typical aplastic anemia (AA), but their implications in the prognosis and in the evolution to hematologic malignancies are controversial.
Methods
We retrospectively analyzed 127 adult AA patients who had successful cytogenetic analysis at initial diagnosis.
Results
The patients were classified into 3 groups according to the initial and follow-up results of cytogenetic profiles. Group 1 included patients who had persistent AA with normal cytogenetic profiles (N=117); Group 2, those who had a normal cytogenetic profile at initial diagnosis but later acquired CA (N=4, 3.1%); and Group 3, those who had CA at the initial diagnosis, regardless of follow-up cytogenetic status (N=6,4.7%). In Group 2, 2 patients later developed CA without progression to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); the other 2 patients later progressed to AML. None of the patients in Group 3 progressed to AML or MDS. There was no significant difference in overall survival between Groups 1 and 3.
Conclusion
AA patients with CA at initial diagnosis or follow-up may not be at greater risk for evolution to AML or MDS, or show shorter survival periods. Prospective studies and a larger patient samples are needed to establish the clinical relevance of CA.
doi:10.5045/kjh.2010.45.4.242
PMCID: PMC3023049  PMID: 21253425
Aplastic anemia; Cytogenetic abnormality

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