Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

Background and Objectives: Even though most of the thyroid cancer shows good prognosis, de-differentiated thyroid cancer is still refractory to conventional treatments. Recently, kinase inhibitors including multi-kinase and BRAF inhibitors are widely used for treatment of de-differentiated thyroid cancers, but resistant to single kinase inhibitor treatment eventually encountered. Therefore, combination therapy may have better therapeutic effect than single therapy for thyroid cancer. In this study, we evaluated therapeutic effect of multi-kinase and BRAF inhibitor combination to anaplastic thyroid cancer cell lines with and without BRAF mutation. Materials and Methods: We used anaplastic thyroid cancer cell lines with BRAF V600E mutation (8505C) and with NRAS mutation (HTh7). Both cell lines were treated with various concentration of multi-kinase inhibitor (lenvatinib) and BRAF inhibitor (vemurafenib). And combination of various concentration of both kinase inhibitors were used to treat both cell lines. Cytotoxic effect was assessed with cell counting kit-8 and therapeutic effect of single kinase inhibitor therapy and the combination therapy was compared. Results: Anti-proliferative effect of vemurafenib on 8505C BRAF V600E -mutated cells was demonstrated from 0.25 μM concentration. However, HTh7 cells with NRAS mutation represented drug resistance up to 4 μM of vemurafenib. In case of lenvatinib treatment as a multi-kinase inhibitor, 8505C and HTh7 cells showed decreased cell viability dose-dependent manner. Combination treatment with vemurafenib and lenvatinib showed synergistic cytotoxic effect in BRAF mutated 8505C cell line, even at lower concentrations. Conclusion Combination treatment with multi-kinase inhibitor and BRAF inhibitor showed promising therapeutic results in BRAF mutated anaplastic thyroid cancer cell line.

BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

STUDY DESIGN: A noninterventional, multicenter, cross-sectional study. PURPOSE: We investigated the prevalence of neuropathic pain (NP) and patient-reported outcomes (PROs) of the quality of life (QoL) and functional disability in Korean adults with chronic low back pain (CLBP). OVERVIEW OF LITERATURE: Among patients with CLBP, 20%–55% had NP. METHODS: Patients older than 20 years with CLBP lasting for longer than three months, with a visual analog scale (VAS) pain score higher than four, and with pain medications being used for at least four weeks before enrollment were recruited from 27 general hospitals between December 2014 and May 2015. Medical chart reviews were performed to collect demographic/clinical features and diagnosis of NP (douleur neuropathique 4, DN4). The QoL (EuroQoL 5-dimension, EQ-5D; EQ-VAS) and functional disability (Quebec Back Pain Disability Scale, QBPDS) were determined through patient surveys. Multiple linear regression analyses were performed to compare PROs between the NP (DN4≥4) and non-NP (DN4 < 4) groups. RESULTS: A total of 1,200 patients (females: 65.7%; mean age: 63.4±13.0 years) were enrolled. The mean scores of EQ-5D, EQ-VAS, and QBPDS were 0.5±0.3, 55.7±19.4, and 40.4±21.1, respectively. Among all patients, 492 (41.0%; 95% confidence interval, 38.2%–43.8%) suffered from NP. The prevalence of NP was higher in male patients (46.8%; p < 0.01), in patients who had pain based on radiological and neurological findings (59.0%; p < 0.01), and in patients who had severe pain (49.0%; p < 0.01). There were significant mean differences in EQ-5D (NP group vs. non-NP group: 0.4±0.3 vs. 0.5±0.3; p < 0.01) and QBPDS (NP group vs. non-NP group: 45.8±21.2 vs. 36.3±20.2; p < 0.01) scores. In the multiple linear regression, patients with NP showed lower EQ-5D (β=−0.1; p < 0.01) and higher QBPDS (β=7.0; p < 0.01) scores than those without NP. CONCLUSIONS: NP was highly prevalent in Korean patients with CLBP. Patients with CLBP having NP had a lower QoL and more severe dysfunction than those without NP. To enhance the QoL and functional status of patients with CLBP, this study highlights the importance of appropriately diagnosing and treating NP.
Adult* ; Back Pain ; Cross-Sectional Studies ; Diagnosis ; Hospitals, General ; Humans ; Linear Models ; Low Back Pain* ; Male ; Neuralgia* ; Prevalence* ; Quality of Life ; Visual Analog Scale

Lemierre's syndrome is characterized by anaerobic bacterial infection in the head and neck, causing thrombophlebitis of the jugular vein. This disease is usually associated with a history of pharyngitis. The most common pathogens are Fusobacterium species, particularly Fusobacterium necrophorum. Lemierre's syndrome is seen most commonly in teenagers and young adults. We present a case report of a 67-year-old man with an atypical clinical manifestation of an uncommon pathogen in Lemierre's syndrome with epilepsia partialis continua.
Adolescent ; Aged ; Bacterial Infections ; Epilepsia Partialis Continua ; Fusobacterium ; Fusobacterium necrophorum ; Head ; Humans ; Jugular Veins ; Lemierre Syndrome* ; Neck ; Pharyngitis ; Thrombophlebitis ; Venous Thrombosis ; Young Adult

Stent thrombosis is a very serious problem after drug-eluting stent (DES) implantation even though its incidence is about or less than 1%. As the clopidogrel resistance is expected to play an important role in the occurrence of stent thrombosis, new anti-platelet agents overcoming this issue can give us another choice. We experienced a case of a 58-year-old male with successful prasugrel rescue therapy in a patient with clopidogrel resistance who had recurrent stent thrombosis following DES implantation.
Drug-Eluting Stents ; Humans ; Incidence ; Male ; Piperazines ; Stents ; Thiophenes ; Thrombosis ; Ticlopidine ; Prasugrel Hydrochloride

PURPOSE: Recently multi-modal imaging system has become widely adopted in molecular imaging. We tried to fabricate animal-specific positioning molds for PET/MR fusion imaging using easily available molding clay and rapid foam. The animal-specific positioning molds provide immobilization and reproducible positioning of small animal. Herein, we have compared fiber-based molding clay with rapid foam in fabricating the molds of experimental animal. MATERIALS AND METHODS: The round bottomed-acrylic frame, which fitted into microPET gantry, was prepared at first. The experimental mice was anesthetized and placed on the mold for positioning. Rapid foam and fiber-based clay were used to fabricate the mold. In case of both rapid foam and the clay, the experimental animal needs to be pushed down smoothly into the mold for positioning. However, after the mouse was removed, the fabricated clay needed to be dried completely at 60 degrees C in oven overnight for hardening. Four sealed pipet tips containing [18F]FDG solution were used as fiduciary markers. After injection of [18F]FDG via tail vein, microPET scanning was performed. Successively, MRI scanning was followed in the same animal. RESULTS: Animal-specific positioning molds were fabricated using rapid foam and fiber-based molding clay for multimodality imaging. Functional and anatomical images were obtained with microPET and MRI, respectively. The fused PET/MR images were obtained using freely available AMIDE program. CONCLUSION: Animal-specific molds were successfully prepared using easily available rapid foam, molding clay and disposable pipet tips. Thanks to animal-specific molds, fusion images of PET and MR were co-registered with negligible misalignment.
Aluminum Silicates ; Animals ; Fungi ; Immobilization ; Magnetic Resonance Imaging ; Mice ; Molecular Imaging ; Veins

PURPOSE: The purpose of this study was to evaluate the anti-tumoral effect of recombinant vaccinia virus (rVV) (Thymidine kinase (-)/GM-CSF (+)) that was administered as a US guided intratumoral injection in a rabbit model of hepatic VX2 carcinoma. MATERIALS AND METHODS: VX2 carcinoma was implanted in the livers of 12 rabbits. US was performed at every week interval to detect hepatic mass after the implantation of VX2 carcinoma. The accurate tumor size and volume was evaluated with CT when the tumor was detected on US. US guided injection of rVV (109 pfu/ml) was preformed in three rabbits, intravenous injection of the same dose of rVV was done in two rabbits and another seven rabbits that were without any treatment were selected as a control group. We evaluated the change of the hepatic tumor size and extrahepatic metastasis on serial CT. Tumor specimens were harvested from rabbits that were killed at 8 weeks after VX2 implantation. These tissues were histoimmuopathologically compared to each other (the virus injection group and the control group). The differences between these groups were statistically assessed with student t-tests. RESULTS: Tumor growth was significantly suppressed in the US guided injection group compared with the intravenous injection group or the control group (p< 0.01). The intravenous injection group showed statistically significant tumor suppression compared to the control group (p< 0.01) until 2 weeks after virus injection. Quantification of the pulmonary metastatic nodules was performed in view of both the number and volume. The average number or volume of the pulmonary metastatic nodules in the US injection group was much smaller than these in the control group. Histopathologically, the tumors of the US guided injection group showed less extensive necrosis than those of the control group. Immunohistochemically, the tumor of the US guided injection group showed more prominent infiltration of CD4 (+) and CD8 (+) lymphocytes than did the tumors of the other group. CONCLUSION: rVV was markedly effective in suppressing hepatic tumor growth and extrahepatic metastasis in a rabbit model of hepatic VX2 carcinoma. US guided intra-tumoral injection was more effective than systemic intravenous injection.
Humans ; Injections, Intravenous ; Liver ; Lymphocytes ; Necrosis ; Neoplasm Metastasis ; Phosphotransferases ; Rabbits ; Vaccinia virus* ; Vaccinia*

A congenital hepatoportal arteriovenous fistula associated with an intrahepatic portal vein aneurysm is a rare type of arteriovenous malformation. Only 14 pediatric cases have been reported to the best of the authors' knowledge. An intrahepatic shunt between the portal and systemic veins is also relatively rare. We report a case of a congenital hepatoportal arteriovenous fistula associated with an intrahepatic portal vein aneurysm and a portohepatic venous shunt in a neonate who presented with tachypnea and melena.
Aneurysm* ; Angiography ; Arteriovenous Fistula* ; Arteriovenous Malformations ; Humans ; Infant, Newborn ; Melena ; Portal Vein* ; Tachypnea ; Veins