TET2 Mutation and High miR-22 Expression as Biomarkers to Predict Clinical Outcome in Myelodysplastic Syndrome Patients Treated with Hypomethylating Therapy.

Tet methylcytosine dioxygenase 2 (TET2) is one of the most frequently mutated genes in myelodysplastic syndrome (MDS). TET2 is known to involve a demethylation process, and the loss of TET2 is thought to cause DNA hypermethylation. Loss of TET2 function is known to be caused by genetic mutations and miRNA, such as miR-22. We analyzed 41 MDS patients receiving hypomethylating therapy (HMT) to assess whether TET2 mutation status and miR-22 expression status were associated with their clinical characteristics and treatment outcomes. Responsiveness to HMT was not affected by both TET2 mutation (odds ratio (OR) 0.900, p = 0.909) and high miR-22 expression (OR 1.548, p = 0.631). There was a tendency for TET2 mutation to be associated with lower-risk disease based on IPSS (Gamma = -0.674, p = 0.073), lower leukemic transformation (OR 0.170, p = 0.040) and longer survival (Hazard ratio 0.354, p = 0.059). Although high miR-22 expression also showed a similar tendency, this tendency was weaker than that of TET2 mutation. In summary, the loss of TET2 function, including both TET2 mutation and high miR-22 expression, was not a good biomarker for predicting the response to HMT but may be associated with lower-risk disease based on IPSS, lower leukemic transformation and longer survival.

The Derived Neutrophil-to-Lymphocyte Ratio Is an Independent Prognostic Factor in Transplantation Ineligible Patients with Multiple Myeloma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. METHODS: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. RESULTS: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015-4.842; p = 0.0458). CONCLUSION: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients.

PURPOSE: Neuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL. METHODS: Cancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed. RESULTS: A total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (n = 722, 95% CI, 32.5-39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96 ± 1.94 versus 4.24 ± 2.02, p < 0.001), and in patients with NCP, pain more severely interfered with daily living, as compared to those without NCP (BPI-SF; 4.86 ± 2.71 versus 4.41 ± 2.87, p < 0.001). Patients with NCP also had worse QOL than those without NCP, as measured by EQ-5D index score (0.47 ± 0.30 vs. 0.51 ± 0.30, p = 0.005), and this was confirmed using multivariate analysis (p < 0.001), even after controlling for other variables such as age, sex, disease stage, cancer duration, radiotherapy, chemotherapy, and comorbidities. Importantly, adjuvant analgesics were used in less than half of patients with NCP (n = 358, 46.4%). CONCLUSIONS: We found that NCP in cancer patients was significantly associated with a worsened QOL, and current management is inadequate. Therefore, future research aimed at developing improved strategies for management of NCP is required.

The role of PET/CT in diagnosing generalized lymphadenopathy in asymptomatic secondary syphilis.

OBJECTIVE: Syphilis is a well-known sexually transmitted disease, and has multiple stages and various symptoms. However, it is difficult to diagnose syphilis in patients who may have no clinical symptoms. Because of these reasons, there have been several case reports on misdiagnosis of syphilis. Generalized lymphadenopathy could be an indication of various diseases including malignancies or infections. CONCLUSION: We report a case of a secondary syphilis in a patient with generalized lymphadenopathy detected by fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) images without any clinical symptom. Clinical examination found an ulcer on his penis and serologic tests set the diagnosis of an early stage of secondary syphilis.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study.

BACKGROUND: In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. METHODS: Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. RESULTS: Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). CONCLUSION: This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

A multicenter retrospective analysis of the clinical features of pernicious anemia in a Korean population.

To determine the approximate incidence and clinical features of pernicious anemia in a Korean population, we retrospectively analyzed clinical data for patients with pernicious anemia who were diagnosed between 1995 and 2010 at five hospitals in Chungnam province. Ninety-seven patients were enrolled, who accounted for 24% of patients with vitamin B(12) deficiency anemia. The approximate annual incidence of pernicious anemia was 0.3 per 100,000. The median age was 66 (range, 32-98) yr, and the male/female ratio was 1.25. Anemia-associated discomfort was the most common symptom (79.4%), followed by gastrointestinal and neurological symptoms (78.4% and 38.1%, respectively). Pancytopenia was found in 36 patients (37.1%), and autoimmune disorders were found in 15 patients (15.5%). Antibody to intrinsic factor was detected in 62 (77.5%) of 80 patients examined, and antibody to parietal cells was detected in 35 (43.2%) of 81 patients examined. Of the 34 patients who underwent tests for Helicobacter pylori, 7 (12.5%) were positive. The anemia-associated and gastrointestinal symptoms resolved completely in all patients after intramuscular injection of cobalamin, whereas neurological symptoms remained in some. In conclusion, pernicious anemia is less frequent in Koreans than in Western populations; however, the clinical features of this disorder in Koreans do not differ from those of Western cases.

Pathophysiological role of hormones and cytokines in cancer cachexia.

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-α, IFN-γ, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-α, IFN-γ, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 ± 19.5 vs 80.9 ± 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.

Expression of AMP-activated protein kinase/ten-eleven translocation 2 and their clinical relevance in colorectal cancer.

Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.

Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial.

PURPOSE: Erlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer. MATERIALS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m² and oxaliplatin 50 mg/m² on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m² on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR). RESULTS: Between 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82-27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34-12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). CONCLUSION: The addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.

Significance of descriptive symptoms and signs and clinical parameters as predictors of neuropathic cancer pain.

PURPOSE: Evaluation of symptoms and signs for the management of neuropathic cancer pain (NCP) is challenging. This study aimed to identify clinical predictors of NCP and symptoms and signs most relevant of those in Korean patients. METHODS: This nationwide, descriptive, cross-sectional, multicenter, observational study included 2,003 cancer patients aged ≥20 years who reported a visual analog scale (VAS) score ≥1 for pain and provided informed consent for participation. The Douleur Neuropathic (DN4) questionnaire (score ≥4) was used to determine symptoms and signs as well as the presence of NCP. RESULTS: The prevalence of NCP was associated with age <65 years [OR, 1.57; 95% CI, 1.270-1.934], disease duration >6 months (OR, 1.57; 95% CI, 1.232-2.012), stage IV cancer (OR, 0.75; 95% CI, 0.593-0.955), history of chemotherapy (OR, 1.74; 95% CI, 1.225-2.472), and moderate-to-severe cancer pain (OR, 2.05; 95% CI, 1.671-2.524) after multivariate analysis. The most common descriptive symptoms of NCP were tingling, electric shock, and pins and needles. For NCP patients in the presence or absence of the clinical predictors, pins and needles (p = 0.001) and painful cold (p<0.001) symptoms were significantly frequent in patients with moderate-to-severe pain. Tingling, numbness, and touch hypoesthesia (p = 0.022, 0.033, 0.024, respectively) were more frequent in those with longer cancer duration and hyperesthesia (p = 0.024) was more frequent in young patients. CONCLUSION: Age <65 years, disease duration >6 months, stage IV cancer, history of chemotherapy, and moderate-to-severe cancer pain, were identified as predictors of NCP. Some symptoms and signs of NCP were associated with these predictors. Further studies are warranted on the pathogenesis and management of NCP with respect to the symptoms and signs, and factors associated with pain severity in Korean patients.

Safety and effectiveness of central venous catheterization in patients with cancer: prospective observational study.

This study investigated the safety and effectiveness of each type of central venous catheters (CVC) in patients with cancer. We prospectively enrolled patients with cancer who underwent catheterization involving a subclavian venous catheter (SVC), peripherally inserted central venous catheter (PICC), or chemo-port (CP) in our department. From March 2007 to March 2009, 116 patients underwent 179 episodes of catheterization. A SVC was inserted most frequently (46.4%). Fifty-four complications occurred (30.1%): infection in 23 cases, malpositioning or migration of the tip in 18 cases, thrombosis in eight cases, and bleeding in five cases. Malpositioning or migration of the tip occurred more frequently with a PICC (P<0.001); infection occurred more often with a tunneled catheter (P=0.028) and was observed more often in young patients (P=0.023). The catheter life span was longer for patients with solid cancer (P=0.002) than for those with hematologic cancer, with a CP (P<0.001) than a PICC or SVC, and for an indwelling catheter with image guidance (P=0.014) than a blind procedure. In conclusion, CP is an effective tool for long term use and the fixation of tip is important for the management of PICC.

GnRH agonist therapy in a patient with recurrent ovarian granulosa cell tumors.

A 65-yr-old woman presented 17 yr status post-hysterectomy with bilateral ovarian salpingo-oophorectomy, attributable to ovarian cancer. She was admitted to our hospital, with multiple cystic liver masses and multiple large seeded masses in her abdomen and pelvic cavity. Histological examination of the pelvic masses demonstrated granulosa cell tumors. After two courses of systemic combination chemotherapy, with paclitaxel and carboplatin, the masses in the abdomen and pelvic cavity increased, and debulking surgery also failed because of peritoneal dissemination with severe adhesion. Finally, she underwent palliative radiotherapy for only the pelvic masses obstructing the urinary and GI tracts, and monthly hormonal therapy with a gonadotrophin-releasing hormone agonist; leuprorelin 3.75 mg IM. Subsequently, multiple masses beyond the range of the radiation as well as those within the radiotherapy field partially decreased. This partial response had been maintained for more than 8 months as of the last follow-up visit. Owing to its long and indolent course and the low metabolic rate of the tumors, advanced or recurrent granulosa cell tumor (GCT) requires treatment options beyond chemotherapy, surgery, and radiotherapy. Hormonal agents may provide another treatment option for advanced or recurrent GCT in those who are not candidates for surgery, chemotherapy, or radiotherapy.

Evaluating the recent developments in palliative chemotherapy for metastatic colorectal cancer.

The incidence of colorectal cancer (CRC) has increased. CRC is the third most common cancer and the fourth most common cause of cancer-related deaths in Korea. Palliative chemotherapy can be used to shrink tumors and ease symptoms caused by the cancer when cure is not possible. It is important to identify chemotherapeutic agents that can be used to effectively treat metastatic CRC (mCRC) and thus improve the survival and quality of life of patients with mCRC. This review aimed to evaluate the recent developments in palliative chemotherapy for mCRC and the biological or targeted agents used based on genetic alterations.

Defensin alpha 6 (DEFA6) is a prognostic marker in colorectal cancer.

Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo. Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro. Furthermore, DEFA6-deficient cancer cells exhibited significantly reduced growth rates compared to control cells in vivo. More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease.

Protein kinase, membrane­associated tyrosine/threonine 1 is associated with the progression of colorectal cancer.

The protein kinase, membrane­associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1­depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient­derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA­mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient­derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer.

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

CORRIGENDUM: Correction of funding statement in ACKNOWLEDGEMENTS section: Epigenetic inactivation of RUNX3 in colorectal cancer.

[This corrects the article on p. 19 in vol. 94, PMID: 29333422.].

Epigenetic inactivation of RUNX3 in colorectal cancer.

PURPOSE: Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. METHODS: Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. RESULTS: Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). CONCLUSION: Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Attenuated FOLFIRINOX in the salvage treatment of gemcitabine-refractory advanced pancreatic cancer: a phase II study.

BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.

The incidence of venous thromboembolism is not lowin Korean patients with advanced pancreatic cancer [corrected]

Background: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. Methods: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. Results: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P<0.001). Even when VTE included SVT, the result was similar (P<0.001). Conclusion: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.