Long-term clinical outcomes after endovascular management of ruptured pseudoaneurysm in patients undergoing pancreaticoduodenectomy

PURPOSE: Recent studies have analyzed the short-term clinical outcomes of ndovascular management. However, the long-term outcomes are unknown. This study aimed to investigate clinical outcomes after endovascular management for ruptured pseudoaneurysm in patients after pancreaticoduodenectomy (PD). METHODS: The medical records of 2,783 patients who underwent PD were retrospectively reviewed at a single center. Of 62 patients who received intervention after pseudonaeurysm rupture, 57 patients (91.9%) experienced eventual success of hemostasis. The patients were composed as follows: (embolization only [EMB], n = 30), (stent-graft placement only [STENT], n = 19) and (both embolization and stent-graft placement simultaneously or different times [EMB + STENT], n = 8). Long-term complications were defined as events that occur more than 30 days after the last successful endovascular treatment. RESULTS: Among 57 patients, short-term stent-graft related complications developed in 3 patients (5.3%) and clinical complication developed in 18 patients (31.5%). Nine (15.8%) had long-term stent-graft related complications, which involved partial thrombosis in 5 cases, occlusion in 3 cases and migration in 1 case. Except for 1 death, the remaining 8 cases did not experience clinical complications. The stent graft primary patency rate was 88.9% after 1 month, 84.2% after 1 year, and 63.2% after 2 years. Of 57 patients, 30 days mortality occurred in 8 patients (14.0%). CONCLUSION: After recovery from initial complication, most of patients did not experience fatal clinical complication during long-term follow-up. Endovascular management is an effective and safe management of pseudoaneurysm rupture after PD in terms of long-term safety.

Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). MATERIALS AND METHODS: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpoint was 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed. RESULTS: Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinib was 2 (range, 0 to 33). Median PFS was 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common. CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

Relationship between Lumbar Extensor Muscle Degeneration Classification and Osteoporotic Vertebral Compression Fracture / 대한척추외과학회지

STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the reliability of the lumbar extensor muscle degeneration classification as an indicator of potential risk for osteoporotic vertebral compression fractures (OVCF). SUMMARY OF LITERATURE REVIEW: Fatty degeneration of lumbar extensor muscles has attracted increased interest in the literature as a risk factor for OVCF. MATERIALS AND METHODS: Ninety-one patients with OVCF (group 1) and 60 patients without OVCF (group 2) were investigated. Magnetic resonance imaging was used to measure and to analyze the muscle mass and fatty degeneration of the lumbar extensor muscle. The degree of fatty degeneration of the lumbar extensor muscle was classified into 4 stages: less than 10%, 10%–25%, 25%–50%, and more than 50%. RESULTS: Fatty degeneration of the lumbar extensor muscle and the bone mineral density T-score were 29.66%±12.28% and −3.56±1.13 in group 1 and 24.04%±13.29% and −2.27±1.46 in group 2, which were statistically significant differences (p < 0.05). Logistic regression analysis revealed that as the fatty degeneration of the lumbar extensor muscle increased, the risk of OVCF increased (odds ratio [OR]=1.21; p=0.01). The risk of OVCF increased as the lumbar extensor muscle degeneration classification scores increased (OR=13.53; p=0.02). Furthermore, as the muscle mass of the multifidus decreased, lumbar lordosis and sacral inclination decreased (β=0.33; p=0.01 and β=0.25; p=0.04, respectively). However, no factor affected thoracic kyphosis. CONCLUSIONS: Fatty degeneration of the lumbar extensor muscle was correlated with OVCF. A lumbar extensor muscle degeneration classification higher than stage 3 should be considered a risk factor of OVCF.

Relationship between Lumbar Extensor Muscle Degeneration Classification and Osteoporotic Vertebral Compression Fracture

OBJECTIVES@#To investigate the reliability of the lumbar extensor muscle degeneration classification as an indicator of potential risk for osteoporotic vertebral compression fractures (OVCF).SUMMARY OF LITERATURE REVIEW: Fatty degeneration of lumbar extensor muscles has attracted increased interest in the literature as a risk factor for OVCF.@*MATERIALS AND METHODS@#Ninety-one patients with OVCF (group 1) and 60 patients without OVCF (group 2) were investigated. Magnetic resonance imaging was used to measure and to analyze the muscle mass and fatty degeneration of the lumbar extensor muscle. The degree of fatty degeneration of the lumbar extensor muscle was classified into 4 stages: less than 10%, 10%–25%, 25%–50%, and more than 50%.@*RESULTS@#Fatty degeneration of the lumbar extensor muscle and the bone mineral density T-score were 29.66%±12.28% and −3.56±1.13 in group 1 and 24.04%±13.29% and −2.27±1.46 in group 2, which were statistically significant differences (p < 0.05). Logistic regression analysis revealed that as the fatty degeneration of the lumbar extensor muscle increased, the risk of OVCF increased (odds ratio [OR]=1.21; p=0.01). The risk of OVCF increased as the lumbar extensor muscle degeneration classification scores increased (OR=13.53; p=0.02). Furthermore, as the muscle mass of the multifidus decreased, lumbar lordosis and sacral inclination decreased (β=0.33; p=0.01 and β=0.25; p=0.04, respectively). However, no factor affected thoracic kyphosis.@*CONCLUSIONS@#Fatty degeneration of the lumbar extensor muscle was correlated with OVCF. A lumbar extensor muscle degeneration classification higher than stage 3 should be considered a risk factor of OVCF.

Triple Combination Chemotherapy in Elderly Metastatic Gastric Cancer Patients / 계명의대학술지

This study was conducted in order to evaluate the response rate, progression free survival (PFS), overall survival (OS), safety and prognostic factors of weekly S-1, paclitaxel plus cisplatin chemotherapy in patients older than 65 years. We administered the triple regimen to patients older than 65 years with recurrent or metastatic gastric cancer. The response rate, PFS, safety of triple combination chemotherapy was evaluated. Clinical outcomes of the elderly group (≥65 years old; n = 28) were compared with those of the non-elderly group (<65 years old; n = 68). The common metastatic lesions were abdominal lymph nodes (57.1%). The median number of cycle was 3.3 cycles (range; 1~9). The disease response rate was 50.0%. The median PFS was 6.2±0.46 months and median OS was 7.6±1.46 months. This treatment was moderately tolerated with grade 3/4 neutropenia in 67.9%, grade 3 anemia in 21.4%. Non-hematologic toxicities were grade 3 general weakness in 25.0% of patients. Compare to younger patients, more grade 3/4 neutropenia, anemia and general weakness were observed. Treatment related mortality was 3.6%. Only body mass index (BMI) was correlated with overall survival by cox regression analysis (p = 0.043). Triple regimen in elderly gastric cancer patients showed relatively high disease response rate and survival duration similar to younger patients, but more frequent neutropenia, anemia and general weakness were seen as barriers to treatment in elderly patients. Especially in low BMI elderly patients, triple regimen chemotherapy must be used with caution.

Intermittent Pneumatic Compression for the Prevention of Venous Thromboembolism after Total Hip Arthroplasty

BACKGROUND: Venous thromboembolism (VTE) is a relatively common and potentially life threatening complication after major hip surgery. There are two main types of prophylaxis: chemical and mechanical. Chemical prophylaxis is very effective but causes bleeding complications in surgical wounds and remote organs. On the other hand, mechanical methods are free of hemorrhagic complications but are less effective. We hypothesized that mechanical prophylaxis is effective enough for Asians in whom VTE occurs less frequently. This study evaluated the effect of intermittent pneumatic compression (IPC) in the prevention of VTE after major hip surgery. METHODS: Incidences of symptomatic VTE after primary total hip arthroplasty with and without application of IPC were compared. A total of 379 patients were included in the final analysis. The IPC group included 233 patients (106 men and 127 women) with a mean age of 54 years. The control group included 146 patients (80 men and 66 women) with a mean age of 53 years. All patients took low-dose aspirin for 6 weeks after surgery. IPC was applied to both legs just after surgery and maintained all day until discharge. When a symptom or a sign suspicious of VTE, such as swelling or redness of the foot and ankle, Homans' sign, and dyspnea was detected, computed tomography (CT) angiogram or duplex ultrasonogram was performed. RESULTS: Until 3 months after surgery, symptomatic VTE occurred in three patients in the IPC group and in 6 patients in the control group. The incidence of VTE was much lower in the IPC group (1.3%) than in the control group (4.1%), but the difference was not statistically significant. Complications associated with the application of IPC were not detected in any patient. Patients affected by VTE were older and hospitalized longer than the unaffected patients. CONCLUSIONS: The results of this study suggest that IPC might be an effective and safe method for the prevention of postoperative VTE.

Portal Vein Stenting for Delayed Jejunal Varix Bleeding Associated with Portal Venous Occlusion after Hepatobiliary and Pancreatic Surgery

OBJECTIVE: The study aimed to describe portal stenting for postoperative portal occlusion with delayed (≥ 3 months) variceal bleeding in the afferent jejunal loop. MATERIALS AND METHODS: Eleven consecutive patients (age range, 2–79 years; eight men and three women) who underwent portal stenting between April 2009 and December 2015 were included in the study. Preoperative medical history and the postoperative clinical course were reviewed. Characteristics of portal occlusion and details of procedures were also investigated. Technical success, treatment efficacy (defined as disappearance of jejunal varix on follow-up CT), and clinical success were analyzed. Primary stent patency rate was plotted using the Kaplan-Meier method. RESULTS: All patients underwent hepatobiliary-pancreatic cancer surgery except two children with liver transplantation for biliary atresia. Portal occlusion was caused by benign postoperative change (n = 6) and local tumor recurrence (n = 5). Variceal bleeding occurred at 27 months (4 to 72 months) and portal stenting was performed at 37 months (4 to 121 months), on average, postoperatively. Technical success, treatment efficacy, and clinical success rates were 90.9, 100, and 81.8%, respectively. The primary patency rate of portal stent was 88.9% during the mean follow-up period of 9 months. Neither procedure-related complication nor mortality occurred. CONCLUSION: Interventional portal stenting is an effective treatment for delayed jejunal variceal bleeding due to portal occlusion after hepatobiliary-pancreatic surgery.

Usefulness of intraopertive ultrasonography during directional atherectomy using SilverHawk/TurboHawk system

PURPOSE: Directional atherectomy (DA) was introduced for the management of infrainguinal arterial stenosis or occlusive lesions. The procedure success rate in the DEFINITIVE LE study was determined using radiologic imaging. The aim of our study was to determine the usefulness of intraoperative ultrasonography (USG) during DA for evaluating the early results of this procedure. METHODS: Patients who underwent DA from January to December 2014 were reviewed retrospectively. Twenty lesions from 14 patients with femoral artery stenosis (>70% stenosis) with short segment occlusive lesions (<2 cm in length) were treated. Among 20 lesions, 3 were treated with the TurboHawk system with a protective device due to lesion calcification. The percentage of stenosis during and after DA was determined with USG. RESULTS: Median follow-up was 5.1 months, and the procedural success rate (<30% stenosis at the end of the procedure) was 100% on angiography, but only 30% on intraoperative USG. On USG, median residual stenosis was 40% (range, 28%–42%) at the end of DA, 40% (range, 30%–55%) at 1 month, 55% (range, 35%–85%) at 6 months, and 64% (range, 60%–100%) at 1 year. There was one dissection, but no cases of perforation, pseudoaneurysm, or thrombosis. Primary patency, which was defined as a peak systolic velocity ratio ≤3.5 with no reintervention at 6 months, was found in 18 lesions (90%), and 11 of 14 patients (78.6%) were free of ischemic symptoms such as claudication at 6 months. CONCLUSION: Our results demonstrated that DA with intraoperative USG is an effective treatment option for short segment occlusive lesions of the femoral artery.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Targeted therapy of ovarian cancer including immune check point inhibitor

Epithelial ovarian cancer is the eighth most common cause of cancer-related deaths in women because most patients present with advanced stage disease at the time of diagnosis. Although cytoreductive surgery and platinum-based chemotherapy remain the gold standards of treatment, the recurrence rate of ovarian cancer remains high. Attempts to improve this standard two-drug chemotherapy by adding a third cytotoxic drug have failed to affect either progression-free survival or overall survival and have resulted in an increase in toxic side effects. Some anti-angiogenic agents, poly(ADP-ribose) polymerase, and immune checkpoint inhibitors have shown efficacy in early stages of development for the treatment of epithelial ovarian cancer. As demonstrated in recent clinical trials, the use of bevacizumab, cediranib, pazopanib, olaparib, and rucaparib, either alone or in combination with conventional cytotoxic agents, improves progression-free survival. Trials on immune checkpoint inhibitors such as nivolumab have revealed prolonged responses in a small set of ovarian cancer cases but require further exploration. In this review, we discuss the role of targeted therapies against ovarian cancer, including the use of immune checkpoint inhibitors.

Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice

OBJECTIVE@#To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice.@*METHODS@#Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis.@*RESULTS@#In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE (50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors mRNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMP-activated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins.@*CONCLUSIONS@#CAE can efficiently regulate BDL-induced liver injury with antioxidant, anti-inflammatory, and anti-apoptotic activities.

Sensitization to animal allergens and allergic symptoms during exposure to them in Korean veterinary researchers

PURPOSE: Veterinary researchers are exposed to variable animal allergens. However, sensitization to them and allergic symptoms during exposure to them in this group are not sufficiently evaluated worldwide, especially in Korea. The objective of this study is to evaluate sensitization to animal allergens and allergic symptoms during exposure to them in Korean veterinary researchers. METHODS: Thirty-two veterinary researchers who participated in the 2016 annual symposium of the Korean Society of Veterinary Science were asked to answer questionnaires regarding allergic symptoms during animal exposure and underwent skin prick tests for animal allergens. Animal allergens consisted of chicken feather and 10 mammals, epithelia as well as cow's milk, hen's egg, and 7 animal types of meat. RESULTS: There were 13 subjects who complained of allergic symptoms during exposure to certain animal epithelia and 19 who did not. Between the 2 groups, there were no differences in age, sex, underlying allergic disease, family history of allergy, current occupation and its duration, numbers and specie of contact animals, or daily contact time. Meanwhile, the sensitization rates to mouse, horse, rabbit, and guinea pig were significantly higher in the symptomatic group. Rhinoconjunctivitis symptoms were the most common allergic symptoms related to animal exposure were most common followed by dermatologic symptom, and symptom of lower respiratory tract. CONCLUSION: We found that sensitizations to some animal epithelia were more frequent in Korean veterinary researchers with allergic symptoms during exposure to animal compared to those without it, and their most common symptoms were rhinoconjunctivitis symptoms.

Anaphylaxis after consumption of abalone

Abalone is popular seafood in Asia; however, allergy to abalone was rarely reported. We report a case of anaphylaxis after consumption of abalone. A 24-year-old female visited an Emergency Department, complaining of cough, dyspnea, rhinorrhea, generalized urticaria, facial edema, and wheezing that had developed 1 hour after consumption of abalone. She was discharged when her symptoms subsided after antihistamine and dexamethasone were given. One month later, she was referred to our outpatient clinic. We performed skin prick tests, measurement of serum specific IgE antibody level, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with IgE immunoblotting. Both skin prick and specific IgE antibody tests were positive for abalone crude extract. In SDS-PAGE with IgE immunoblotting, we identified possible antigens sized 55, 100, and 25 kDa, respectively. This is the first case of abalone-induced anaphylaxis in Korea.

Impaired Empathic Abilities among Patients with Complex Regional Pain Syndrome (Type I)

OBJECTIVE: The aims of this study were to evaluate differences in empathic abilities between patients with complex regional pain syndrome (CRPS) Type I and healthy control subjects (HCs) and to assess correlations between empathic abilities and multidimensional aspects of pain. METHODS: Empathic ability was measured in 32 patients with CRPS Type I and in 36 HCs using the Interpersonal Reactivity Index (IRI). A comprehensive assessment of pain was conducted in the patient group using the West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Psychiatric symptoms were assessed using the Beck Depression and Anxiety Inventories (BDI and BAI), and quality of life was evaluated using the WHO Quality of Life (WHOQOL-BREF) questionnaire. RESULTS: Patients with CRPS showed impaired cognitive and emotional empathic abilities compared with HCs. Significantly lower levels of perspective taking and empathic concern and higher levels of personal distress on the IRI were exhibited by the patient group. Perspective taking and personal distress were associated with affective distress and poor quality of life in social contexts (BDI, BAI, and WHOQOL). However, empathic concern was positively correlated with pain severity and social support from others (WHYMPI). CONCLUSION: A tendency toward self-oriented distress in social cognition was exhibited among patients with CRPS Type I. Impaired empathic ability was shown to have potentially negative effects on subjective emotional outcomes and social performance in the lives of patients. Interventions to improve emotional awareness and theory of mind would be beneficial for enhancing social functioning in patients with CRPS Type I.

Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer. MATERIALS AND METHODS: A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS). RESULTS: In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle. CONCLUSION: Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.

Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice

Objective To evaluate the possible protective effect of Citrus aurantium peel extract (CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. Methods Male ICR mice were divided to 5 groups: 1) Control group (Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation (BDL), 3) BDL mice treated with silymarin (200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis. Results In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE (50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma-glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors mRNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMP-activated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins. Conclusions CAE can efficiently regulate BDL-induced liver injury with antioxidant, anti-inflammatory, and anti-apoptotic activities.

Characteristics and Trends of Published Adult Hip Research over the Last Decade

PURPOSE: We designed this study to demonstrate recent trends in the proportion of adult hip research in orthopedics, to identify countries leading the adult hip research, and to evaluate the relationship between the economic power of the countries and their contributions. MATERIALS AND METHODS: Studies published in seven select orthopedic journals were retrieved from PubMed. Among them, we determined the number of adult hip studies. The countries-of-origin of adult hip studies, and the economic power of the countries were investigated. RESULTS: A total of 7218 orthopedic publications and 1993 (27.6%) addressed adult hip research were identified. Adult hip studies increased from 313 (23.7%) in 2000 to 555 (27.9%) in 2011. Twenty-five countries accounted for 97.6% of the total number of adult hip studies, and gross domestic product correlated with publication volume (Spearman's rho, 0.723; p=0.000). CONCLUSION: Researchers from a limited number of developed countries have published their studies in the adult hip discipline.

The Result of Revision Total Hip Arthroplasty in Patients with Metallosis Following a Catastrophic Failure of a Polyethylene Liner

BACKGROUND: Wear cannot be completely prevented after total hip arthroplasty. If severe polyethylene (PE) liner wear develops, the so-called catastrophic failure occurs and metallosis develops. We postulated that longevity of the new implant may be affected after revision surgery for metallosis following a catastrophic failure of a PE liner due to the substantial amount of PE wear particles and infiltration of the metal particles in this catastrophic condition. METHODS: Twenty-three hips of 23 patients were identified because they showed metallosis during revision total hip arthroplasties performed in Seoul National University Hospital between January 1996 and August 2004. They were followed for at least 6.5 years after the index revision total hip arthroplasty. The clinical and radiological results of revision total hip arthroplasties in these patients were evaluated. RESULTS: The median Harris hip score increased from 60 points before revision total hip arthroplasties to 90 points at the final follow-up. Osteolysis was detected at an average of 9.3 years after revision total hip arthroplasties in 13 hips and acetabular cup loosening at average 9.8 years after revision total hip arthroplasties in 9 hips. With radiographic evidence of osteolysis and loosening as the end points, the 15-year survival rates were 28.2% and 56.0%, respectively. CONCLUSIONS: The survival rate of revision total hip arthroplasty in patients with metallosis following a catastrophic failure of a PE liner was low.

Metachronous Double Primary Cancer after Treatment of Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The pattern of double primary cancer after treatment for breast cancer is important for patient survival. MATERIALS AND METHODS: We analyzed 108 cases of metachronous double primary cancer in breast cancer patients treated from 1999 to 2012. RESULTS: Metachronous double primary cancers occurred in 108 of 2,657 patients (4.1%) with breast cancer. The median time to the occurrence of second cancer after diagnosis of the first was 58.4+/-41.2 months (range, 6.9 to 180.2 months). The most common cancer was thyroid cancer, which occurred in 45 patients (41.7%). This was followed by gastric cancer in 16 patients (14.8%), endometrial cancer in 10 patients (9.3%), and cervical cancer in seven patients (6.5%). The relative risk showed a significant increase in endometrial (4.78; 95% confidence interval [CI], 1.66 to 13.79), gastric (2.61; 95% CI, 1.68 to 4.06), and thyroid cancer (1.95; 95% CI, 1.37 to 2.79). At 5 years after diagnosis of breast cancer, secondary cancer occurred in 48 patients (44.4%), with 50.0% of the endometrial, 56.3% of the stomach, and 37.8% of the thyroid cancer cases being diagnosed after 5 years. Median survival after diagnosis of the second cancer was 123.9+/-11.2 months. The prognosis was mainly influenced by the anatomic site. CONCLUSION: The incidence of endometrial, stomach, and thyroid cancer increased significantly after treatment with primary breast cancer, and survival was dependent on early detection and the type of second primary cancer. A prolonged follow-up examination for metachronous double primary cancer is needed to provide early detection and improve survival time in patients with breast cancer.