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Radiographic factors estimate the state of the static knee joint, and it is questionable how well these parameters reflect the dynamic knee condition. The external knee adduction moment (KAM) during gait is known to be a kinetic variable contributing to osteoarthritis progression. This study aims to investigate the effects of static radiographic parameters on the dynamic KAM during gait.Overall, 123 patients (mean age, 65.7 years; standard deviation, 8.1 years; 34 men and 89 women) were included. Seven radiographic parameters including the mechanical tibiofemoral angle (mTFA), Kellgren-Lawrence grade, and ankle joint line orientation (AJLO) were measured on radiographs, and the maximum KAM and KAM-time integral in the stance phase were obtained using three-dimensional gait analysis. The correlation and multiple regression analyses were performed for identifying significant radiographic measurements associated with the KAM.Most of the radiographic measurements correlated with the maximum KAM and KAM-time integral. As a result of multiple regression analysis, the mTFA (p 0.001) and AJLO (p = 0.003) were identified as significant factors associated with the KAM-time integral (RThe mTFA and AJLO were significantly associated with the KAM. However, to be used as a surgical indication for corrective osteotomy, a longitudinal study is needed to validate whether the mTFA and AJLO values directly cause osteoarthritis progression as we have suggested.III.

Study design Prospective observational study. Objective The aim of this study was to investigate the improvement in gait parameters after surgery and whether corrective surgery for sagittal imbalance would be influenced by preoperative pelvic compensation. Summary of background data There have been no other studies investigating the influence of preoperative pelvic compensation on surgical outcomes. Methods A total of 32 patients who were scheduled to undergo corrective surgery for sagittal plane deformity were included and were followed-up for 1 year after surgery. Radiological parameters were measured on biplanar full-body imaging. Before surgery and 6 months after surgery, three-dimensional motion analyses were performed to estimate center of gravity (CoG) deviation from the center of mass (CoM), mean trunk kyphosis (TK) angle, gait deviation index (GDI), and kinematic parameters. Before surgery, the patients were classified into CoG+ and CoG- groups. "+" and "-" representing increases and decreases in the distance of CoG from CoM of the pelvic segment from first to third trials, respectively. Oswestry Disability Index (ODI) and EuroQol-5D (EQ-5D) were measured for 1 year after surgery. Results All radiological parameters improved significantly after surgery. For gait parameters, CoG from CoM, mean TK angle, and minimum angle of the hip and knee joints in the stance phase during walking were significantly decreased after surgery and GDI scores significantly improved after surgery. The mean changes of the CoG distance from the CoG and the mean TK from first to third trials of gait analysis significantly decreased postoperatively. There were no significant differences in ODI and EQ-5D scores over 1-year follow-up assessment between CoG+ and CoG- groups. Conclusion Preoperative abnormal stooping gait, and progressive worsening of sagittal imbalance in patients with sagittal plane deformity improved after corrective surgery. Patients with preoperative dynamic sagittal imbalance could have similar surgical results to those without it after corrective surgery. Level of evidence 3.

Purpose This study aimed to (1) quantitatively analyze the fibular footprints of the lateral collateral ligament (LCL) and popliteofibular ligament (PFL) and (2) evaluate whether a fibular tunnel can restore the LCL and PFL fibular footprints simultaneously without modification in anatomic posterolateral corner reconstruction of the knee. Methods In 20 cadaveric knees, anatomic characteristics, such as diameter, location and relationship with anatomic landmarks, of the LCL and PFL footprints were analyzed. Subsequently, a fibular tunnel that connected the LCL and PFL footprint centers was created with 1.5 mm drill bit, and tunnel depth, which is defined as the distance between the tunnel and the nearest cortex, was evaluated. An additional tunnel from the anteroinferior border of the LCL footprint to the posteroinferior border of the PFL footprint was created, and its tunnel depth was evaluated as well and compared with that of the original tunnel. Results The LCL footprint was longitudinally ovoid (8.4 ± 1.0 × 13 ± 1.0 mm), and its inferior margin corresponded well with the lateral apex of the fibula (distance, 1.0 ± 0.7 mm). The PFL footprint was round (9.7 ± 1.3 × 9.0 ± 1.1 mm), and its center was very close to the tip of the fibular styloid process (1.2 ± 0.8 mm). The tunnel depth of the original fibular tunnel was 1.8 ± 0.7 mm, and it was very shallow for tunnel reaming. On the contrary, the tunnel depth of the modified fibular tunnel (6.4 ± 1.1 mm) was significantly higher than that of the original tunnel (P Conclusions A single fibular tunnel cannot reproduce the LCL and PFL footprint centers simultaneously because the trajectory is too close to the cortex. A modified fibular tunnel, using the margins of the footprints, is recommended to avoid cortical blowout. Clinical Relevance A modified fibular tunnel that covers only portions of the LCL and PFL footprints, from the anteroinferior LCL footprint to the posteroinferior PFL footprint, is less likely to blow out the lateral fibula than is a similar tunnel using the anatomic footprint centers.

BACKGROUND CONTEXT Biportal endoscopic decompressive laminectomy is a widely performed procedure and shows acceptable clinical outcomes. However, the evidence regarding the advantages of biportal endoscopic surgery is weak, a randomized controlled trial is therefore warranted. PURPOSE To compare the clinical efficacies of biportal endoscopic and microscopic decompressive laminectomy in patients with lumbar spinal stenosis. STUDY DESIGN Randomized controlled trial. PATIENT SAMPLE Sixty-four participants suffering from low back and leg pain with single-level lumbar spinal stenosis who required decompressive laminectomy. OUTCOME MEASURES Outcomes were assessed with the use of patient-reported outcome measures, visual analog scale (VAS) score for low back and lower extremity radiating pain, Oswestry disability index (ODI), European Quality of Life-5 Dimensions (EQ-5D) score, and painDETECT for neuropathic pain. Surgery-related outcomes including operation time, length of hospital stay, postoperative drainage, and serum creatine phosphokinase were evaluated. Perioperative ( METHODS All participants were randomly assigned in a 1:1 ratio to undergo biportal endoscopic or microscopic decompressive laminectomy. The primary outcome was the ODI score at 12 months after surgery based on a modified intention-to-treat strategy. The secondary outcomes included VAS score for low back and lower extremity radiating pain, ODI scores, EQ-5D score, and painDETECT score. There were no sources of funding and no conflicts of interest associated with this study. RESULTS There was no significant difference between groups in the mean ODI score at 12 months after surgery (30 in the microscopy vs. 29 in the biportal endoscopy group, p=.635). There were also no significant differences in low back and lower extremity pain VAS scores, ODI, EQ-5D scores, and painDETECT scores at the 3-, 6-, or 12-month follow-up. Operation time, length of hospital stay, serum creatine phosphokinase, and perioperative complications, such as durotomies and symptomatic hematoma, showed no significant differences between the groups; however, one participant underwent additional revision surgery 9 months after the index surgery in the microscopy group. CONCLUSIONS Despite the study design limitation of relatively short duration of follow-up, this trial suggests that biportal endoscopic decompressive laminectomy is an alternative to and offers similar clinical outcomes as microscopic open surgery in patients with symptomatic lumbar spinal stenosis.

This study aimed to examine which motion analysis parameters regarding the dynamic aspects and/or balance affect the development acute proximal junctional kyphosis (PJK) following adult spinal deformity (ASD) surgery. A total of 90 consecutive patients were recruited prospectively, who underwent a corrective surgery for ASD with sagittal imbalance. According to the development of acute PJK within 6 months after surgery, the patients were divided into the PJK+ and PJK− groups. Before surgery, three-dimensional gait analyses were performed using a motion analysis system. The preoperative continuous and categorical variables were compared between the PJK+ and PJK− groups using independent t tests and chi-square tests, respectively. Finally, a multivariate logistic regression model was used to identify the risk factors and calculate the odds ratio (OR) for acute PJK. A total of 20 and 70 patients were classified into the PJK+ and PJK− groups, respectively. There were no differences in the spinopelvic radiologic parameters pre- and postoperatively between the PJK+ and PJK− groups. The PJK+ group showed a significantly higher mean anterior pelvic tilt (Ant-PT) angle in preoperative motion analysis than the PJK− group (P = 0.001 for both sides). Multivariate analysis identified the mean Ant-PT angle (P = 0.047; OR 1.127; 95% CI 1.002–1.267) as a significant risk factor for acute PJK. Preoperative Ant-PT angle during walking was associated with a higher OR in acute PJK after surgery.

The purpose of our study was to evaluate the incidence and to identify risk factors of subsequent vertebral fractures after hip fractures, and to determine whether the subsequent vertebral fracture increases the mortality rate of elderly hip fracture patients. From January 2009 to July 2016, 1,554 patients were diagnosed as having a hip fracture and were treated surgically at our institution. Among them, 1121 patients age > 50 years at the time of injury and were followed up for 1 year or longer after the hip fracture surgery. In these patients, radiographs of the hip and spine were taken at each follow-up. We reviewed medical records and radiographs of these patients. Among the 1121 patients, 107 patients (9.5%) had subsequent vertebral fractures after the hip fracture during entire follow-up periods. In multivariable analysis, previous history of vertebral fracture [odds ratio (OR), 2.62; p

Background Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child–Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child–Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child–Pugh B cirrhosis. Methods Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. Results Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child–Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P Conclusion Patients without preoperative portal hypertension and Child–Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.

PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (≥ 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR ≥ 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Knee pain is one of the most common symptoms of knee osteoarthritis (OA) that affects the quality of life in the older adults, and identifying the contributing factors of knee pain is important. We hypothesized that higher fruit and vegetable consumption might be associated with the severity of knee pain lower prevalence of severe knee pain by affecting pain perception in the knee joint. Therefore, we investigated the relationship between self-reported knee pain and the consumption of fruits vegetables, carotenoids and vitamin C and self-reported knee pain. Nationally representative cross sectional study. 2010-2011 rounds of the Korean National Health and Nutrition Examination Survey. A total of 6588 subjects aged ≥50 years were participated. Severity of knee pain was estimated using a 10-point numeric rating scale (NRS). Daily intake of fruits, vegetables, and vitamins were estimated using data from 24-hour recalls and food frequency questionnaires. The NRS scores of knee pain decreased significantly with increasing fruit and vegetable intake quartiles. A multivariate logistic regression analysis showed that the fourth quartile of vegetable and fruit consumption was associated with decreased prevalence of severe knee pain (OR 0.59, 95% CI 0.48-0.73) compared with first quartile of vegetable and fruit consumption; however, carotenoids and vitamin C consumption was not associated with the severity of knee pain. In conclusion, severe knee pain was independently associated with fruit and vegetable consumption. Our findings suggest that intake of whole fruits and vegetables may help improve knee pain in older adults.

In the absence of randomized controlled data and even propensity-matched data, indications for, and outcomes of, laparoscopic repeat liver resection for hepatocellular carcinoma (HCC) remain uncertain. This study aimed to clarify the current indications for laparoscopic repeat liver resection for HCC, and to evaluate outcomes.Forty-two liver surgery centres around the world registered patients who underwent repeat liver resection for HCC. Patient characteristics, preoperative liver function, tumour characteristics, surgical method, and short- and long-term outcomes were recorded.Analyses showed that the laparoscopic procedure was generally used in patients with relatively poor performance status and liver function, but favourable tumour characteristics. Intraoperative blood loss (mean(s.d.) 254(551) versus 748(1128) ml; P 0·001), duration of operation (248(156) versus 285(167) min; P 0·001), morbidity (12·7 versus 18·1 per cent; P = 0·006) and duration of postoperative hospital stay (10·1(14·3) versus 11·8(11·8) days; P = 0·013) were significantly reduced for laparoscopic compared with open procedures, whereas survival time was comparable (median 10·04 versus 8·94 years; P = 0·297). Propensity score matching showed that laparoscopic repeat liver resection for HCC resulted in less intraoperative blood loss (268(730) versus 497(784) ml; P = 0·001) and a longer operation time (272(187) versus 232(129); P = 0·007) than the open approach, and similar survival time (12·55 versus 8·94 years; P = 0·086).Laparoscopic repeat liver resection is feasible in selected patients with recurrent HCC.Dado que no existen ensayos clínicos controlados ni estudios de datos emparejados por puntaje de propensión, todavía hay dudas sobre las indicaciones y los resultados de la resección iterativa laparocópica de un carcinoma hepatocelular (hepatocellular carcinoma, HCC). Este estudio tuvo como objetivo esclarecer las indicaciones actuales y los resultados de la resección hepática laparoscópica iterativa del HCC. MÉTODOS: Se incluyeron los pacientes de 42 centros de cirugía hepática a nivel mundial en los que se había realizado una resección hepática iterativa por HCC. Se analizaron las características del paciente, la función hepática preoperatoria, las características del tumor, el abordaje quirúrgico y los resultados a corto y largo plazo.El análisis demostró que la vía laparoscópica generalmente se utilizaba en pacientes con carácteristicas tumorales favorables, pero con estado funcional y función hepatica relativamente peores. La pérdida de sangre intraoperatoria (254,3 ± 551,2 versus 748,0 ± 1127,7 mL, P 0,001), la duración de la intervención (247,6 ± 155,8 versus 285,1 ± 167,0 minutos, P 0,001), la morbilidad (12,7 versus 18,1%, P = 0,005) y la estancia hospitalaria postoperatoria (10,07 ± 14,29 versus 11,80 ± 11,79 días, P = 0,010) fueron significativamente menores para los pacientes tratados por via laparoscópica en comparacion con la vía abierta, mientra que el tiempo de supervivencia fue comparable (mediana 10,04 versus 8,94 años, P = 0,297). El estudio de emparejamiento por puntaje de propensión mostró que la resección hepática iterativa por vía laparoscópica de un HCC (frente a la vía abierta) conllevaba una menor pérdida sanguínea intraoperatoria (268,0 ± 730,2 versus 496,5 ± 784,2 mL, P = 0,01), una mayor duración de la intervención (272,1 ± 187,2 versus 231,8 ± 129,1 minutos , P = 0,07) y un tiempo de supervivencia similar (mediana 12,55 versus 8,94 años, P = 0,0855). CONCLUSIÓN: La resección hepática iterativa por vía laparoscópica es factible en pacientes seleccionados con HCC recidivado.

In the published article, “Ho Sung Han, Chong Bum Chang, Duk-Chul Lee and Jee-Yon Lee, Relationship between total fruit and vegetable intake and self-reported knee pain in older adults. The journal of nutrition, health & aging. 21, 750–758 (2017), the affiliations were published incorrectly. The authors apologize for any inconvenience that it may have caused.

It is known that ultrasound affects action potentials in neurons, but the underlying principles of ultrasonic neural stimulation are not clearly elucidated yet. In this study, we measured the action potentials of rat hippocampal neurons cultured on multi-electrode arrays during ultrasound stimulation. From most of electrodes, it was observed that the ultrasound stimulation increased the frequencies of action potentials (i.e., spikes) during ultrasound stim- ulation.

AIM For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P

Background Capsaicin is an ingredient of red peppers that binds to transient receptor potential vanilloid subtype 1 (TRPV1), and Koreans eat more capsaicin-rich food than do Japanese. This study aimed to compare symptom generation according to TRPV1 genotypes and the intake of spicy foods. Methods Consecutive functional dyspepsia (FD) patients who were evaluated at Konkuk University Medical Centre (Korea) and Keio University Hospital (Japan) were included. Questionnaires on spicy food intake, patient assessment of gastrointestinal symptoms (PAGI-SYM), patient assessment of quality of life, and hospital anxiety and depression scale were provided. Blood was sampled for the detection of TRPV1 polymorphisms, and upper gastrointestinal endoscopy was performed with biopsies. Key Results Of 121 included subjects, 35 and 28 carried the TRPV1 CC and GG genotypes, respectively, with the prevalence rates not differing between Japan and Korea. The prevalence of FD subtypes did not differ with the spicy food intake, TRPV1 genotypes, or Helicobacter pylori infection. Neither TRPV1 polymorphisms nor H. pylori infections were related to scores on the PAGI-SYM questionnaires, but spicy food intake was positively correlated with the scores for stomach fullness (p = 0.001) and retching (p = 0.001). Using the linear regression analysis, stomach fullness was associated with spicy food intake (p = 0.007), whereas retching was related to younger age (p < 0.001) and female gender (p = 0.014). Conclusions & Inferences Upper gastrointestinal symptoms are more common in subjects with a higher consumption of spicy foods, younger age and female gender, regardless of TRPV1 genotypes and the H. pylori infection status. Capsaicin-rich foods may induce stomach fullness.

Background : We investigated the relationship between resumption or persistence of menstruation after chemotherapy and disease free survival (DFS) in premenopausal patients with early breast cancer. Patients and methods : A total of 843 patients diagnosed with a stage I to III breast cancer between March 2001 and December 2006 were included in this study. All patients received cytotoxic chemotherapy after surgery; 411 (48.8%) with anthracycline based, 416 (49.3%) with anthracycline and taxane containing, and 16 (1.9%) with other regimens. We reviewed the medical records with a long term follow-up. Results : The median age of patients was 41 years (range, 21–54 years) and the median follow-up duration was 6.2 years (range, 0.7−10.4 years). Of all, 632 (75%) patients were hormone receptor (HR) positive who received tamoxifen therapy upon completion of chemotherapy. The chemotherapy induced amenorrhea (CIA) rate was 78.1% (n=658) and 52.4% (n= 442) experienced the resumption of period during the long term follow-up. One hundred two (12.1%) patients had persistent menstruation without CIA. The disease free survival (DFS) was significantly affected by the younger age (≤ 35 years) (HR=1.58, [95% CI, 1.10−2.70], P=0.014), advanced stage (stage 3) (HR=4.45, [95% CI, 3.17−6.25], P Conclusions : A considerable proportion of premenopausal patients treated by chemotherapy experienced resuming period after CIA. The resumption or persistence of menstruation was a poor prognostic factor for disease free survival in premenopausal patients with early breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-24.

Background: ABCB1 polymorphisms could predict treatment results of taxane therapy in several malignancies. FCGR2A and FCGR3A polymorphisms were associated with clinical outcomes in several diseases after treatment with monoclonal antibody drugs which had antibody-dependent cell-mediated cytotoxicity activity. These polymorphisms could be possible predictive markers after taxane plus trastuzumab (TH) chemotherapy in patients with HER-2-positive metastatic breast cancer (MBC). Methods: Fifty-seven patients with HER-2 FISH positive MBC who received TH chemotherapy as the 1st-line treatment were enrolled. We analyzed 5 polymorphisms using DNA from peripheral blood mononuclear cells: ABCB1 1236C>T (rs1128503), ABCB1 2677G>T/A (rs2032582), ABCB1 3435C>T (rs1045642), FCGR2A 131H/R (rs1801274), and FCGR3A 158V/F (rs396991), then correlated them to treatment results of patients. Results: Among 57 patients, 22 patients (38.6%) received weekly paclitaxel plus trastuzumab, 26 patients (45.6%) tri-weekly paclitaxel plus trastuzumab, and 9 patients (15.8%) tri-weekly docetaxel plus trastuzumab. After a median follow-up of 30.6 (range, 0.6-75.9) months, median progression-free survival (PFS) was 15.1 (95% confidence interval (CI), 10.3-19.8) months. ABCB1 2677T allele carriers had longer PFS than the others (42.1 (95% CI, 12.7-71.4) months vs. 13.0 (95% CI, 10.6-15.4) months; p=0.037) along with a tendency toward higher response rate (RR) (86.4% vs. 76.0%; p=0.470) and longer overall survival (OS) (54.7 (95% CI, 43.0-66.4) months vs. 38.9 (95% CI, 18.1-59.7) months; p=0.057). In addition, ABCB1 3435CC genotype carriers had shorter PFS than the others (13.0 (95% CI, 10.8-15.2) months vs. 19.1 (95% CI, 0.0-38.5) months; p=0.039) along with a tendency toward lower RR (78.6% vs. 100%; p=0.567) and shorter OS (38.9 (95% CI, 19.7-58.1) months vs. 54.7 (95% CI, 43.0-66.4) months; p=0.093). ABCB1 1236C>T, FCGR2A 131H/R, and FCGR3A 158V/F were not significantly associated with RR, PFS, and OS. None of these polymorphisms were associated with any grades of hematologic or cardiac toxicities. Conclusions: Our results support that ABCB1 2677G>T/A and 3435C>T may have predictive roles after the 1st-line TH chemotherapy in patients with HER-2-positive MBC. In contrast, ABCB1 1236C>T, FCGR2A 131H/R, and FCGR3A 158V/F could not predict response after TH treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-36.

We conducted a prospective randomized trial to compare laparoscopy-assisted distal gastrectomy (LADG) including lymphadenectomy with open distal gastrectomy for the management of early gastric cancer (EGC).Forty-seven patients who had been diagnosed endoscopically with EGC were included in a study that ran from November 2001 to August 2003. With the aid of random number table, 23 patients were assigned to the open group (group O) and 24 patients were assigned to the LADG group (group L).Estimated blood loss and transfusion amounts were similar in the two groups. The mean postoperative hospital stay and the duration of analgesic administration were shorter for group L but not significantly so. The mean number of harvested lymph nodes was 38.1 in the O group and 31.8 in the L group (p = 0.098). Postoperative pulmonary complications occurred more frequently in the O group (p = 0.043). At a median follow-up of 14 months, there has been no recurrence of disease in either group.In terms of resulting in fewer pulmonary complications while maintaining the curability of EGC, LADG has a clear advantage over its open counterpart.

Cationic starch ethers of normal and waxy corn, normal and waxy barley and normal pea starch were prepared by an aqueous alcoholic process for evaluation of their functional properties as compared to the native starch controls. The native starches exhibited a wide range in average granule size (10–21 μm diameter), amylose content (0–34%) and swelling power (13–31). Cationization to degrees of substitution (DS) of 0.030–0.035 with 3-chloro-2-hydroxypropyltrimethylammonium chloride resulted in marked increases in swelling power of all starches, with little corresponding increases in starch solubility. Cationization also decreased the onset of endothermic transitions and pasting temperatures quite substantially, and promoted the development of sharp peak viscosities in the amylographs of all normal and waxy starches, including that of pea starch. Final cold viscosities of the cationic starches exhibited positive setbacks, and the cooked starch gels, after storage for 7 days at 4°C and −15°C, showed no syneresis. All cationic starches except for waxy corn were more susceptible to α-amylase hydrolysis than native control starches. The general improvement in functional properties, especially in the waxy corn, waxy barley and pea starches, due to the aqueous alcoholic-alkaline cationization process would greatly enhance their industrial applications.

Introduction Preeclampsia (PE) is a leading cause of maternal and neonatal mortality and morbidity worldwide. However, the pathophysiology of this disease is not yet fully understood. MiRNA plays an important role in post-transcriptional gene regulation. Recent studies have suggested that dysregulation of miRNAs in placental tissue is involved in the pathogenesis of PE. Therefore, we investigated miRNA profiles in PE placenta to understand the miRNA function in PE pathogenesis. Methods MiRNA profiling was performed in 20 formalin-fixed and paraffin-embedded samples (10 placentas from severe PE and 10 from a control group). We used a hybridization-based microarray with a PNA-probe comprised of 158 miRNAs. Results Thirteen miRNAs (miR-92b, miR-197, miR-342-3p, miR-296-5p, miR-26b, miR-25, miR-296-3p, miR-26a, miR-198, miR-202, miR-191, miR-95, and miR-204) were significantly overexpressed and two miRNAs (miR-21 and miR-223) were underexpressed in PE compared with the control group. Among 15 differentially expressed miRNAs, miR-26b, miR-296-5p, and miR-223 were found to be consistent with results from previous studies. We identified 893 genes that were predicted by at least three of four computational algorithms. Target genes participated in several signaling pathways, adherens junction, focal adhesion, and regulation of the actin cytoskeleton. Conclusions Several miRNAs are found to be dysregulated in placentas of PE patients and they seem to be closely associated with the early pathogenesis of PE. Further study is necessary to develop tools for early detection and management.

Background Ethnic differences in treatment-related toxicities exist between Eastern and Western patients. Our previous retrospective study has demonstrated racial differences in acute toxicities in patients receiving anthracycline-based chemotherapy. In this retrospective study, we aimed to compare the difference in tolerance to adjuvant docetaxel-cyclophosphamide (TC) between patients of different ethnicities. Methods Data were collected from six international breast cancer centres at which patients were planned for treatment with adjuvant TC (docetaxel 60–75 mg/m 2 and cyclophosphamide 600 mg/m 2 every 21 day for four cycles). Haematological toxicities were assessed by first episode of grade 2 or higher toxicity and disease-free survival was also evaluated. Findings From March 2004 to July 2013, 127 Asian patients (80 Chinese, 46 Japanese, and one Filipino) and 100 Caucasian patients were retrospectively compared for treatment-related toxicities. Baseline demographics and tumour characteristics were different between Asians and Caucasians. When compared to Caucasians, more Asians were premenopausal (61/126, 48.4% versus 30/95, 31.6%; p = 0.013) and less obese (6/127, 4.7% versus 21/100, 21.0%; p p p = 0.027). During the four cycles of chemotherapy, Asians had a significant higher rate of grade ⩾ 2 neutropenia than Caucasians (58/127, 45.7% versus 6/100, 6.0%; p p = 0.046) (table). Differences in grade ⩾ 3 neutropenia were also noted (39/127, 30.7% versus 4/100, 4.0%, p p = 0.764). Other hematological and non-hematological toxicities were much the same between the two ethnic groups. Of 205 patients eligible for survival analysis, 188 (91.7%) patients were disease-free and no significant difference in disease-free survival was observed between Asians and Caucasians at a median follow-up of 23 months. Interpretation Ethnic differences in toxicity profile were noted between Asian and Caucasian patients receiving TC, suggesting the possibility of different pharmcogenomics between ethnic groups. Further validation is essential to underpin differential treatment paradigms for various ethnic groups.

Background Inflammation frequently accompanies gallbladder carcinoma (GBC), but its impact on outcome is unclear. The present study investigated the impact of concomitant inflammation on survival of patients with GBC. Methods All patients undergoing surgery for GBC between October 2003 and May 2009 were identified retrospectively from a prospectively collected database. Patients were classified according to whether preoperative inflammation was present (65 patients) or not (23). Results A total of 88 patients were enrolled. There were no differences in sex, mean age, tumour node metastasis (TNM) stage and radicality of resection between the two groups. The overall 3-year survival rate was lower in patients with preoperative inflammation than in those without (33 versus 73 per cent; P = 0·001). In univariable analysis, preoperative inflammation, T, N and M category, TNM stage, radicality of surgery and tumour differentiation were significant prognostic factors. The presence of preoperative inflammation (hazard ratio (HR) 2·38, 95 per cent confidence interval 1·04 to 5·43), lymph node metastases (HR 5·23, 1·05 to 26·09) and R1 or R2 resection (HR 3·77, 1·47 to 9·72) were independent prognostic factors for poor survival. Conclusion The presence of preoperative inflammation is an independent prognostic factor for poor survival in patients with GBC.

BackgroundThis study evaluated the short- and long-term patency of preserved splenic vessels after laparoscopic spleen-preserving distal pancreatectomy (SPDP) with preservation of the splenic vessels.MethodsThis single-centre retrospective study included all patients who had undergone splenic vessel-preserving laparoscopic SPDP between 2004 and 2007. The patency of the splenic vessels was assessed by abdominal computed tomography and classified into three grades according to the degree of stenosis.ResultsTwenty-two patients were included. The preoperative patency of the splenic artery and vein was normal in 20 and 19 patients respectively. Normal patency of the splenic artery and vein was observed in 16 and five patients respectively within 1 month of surgery, and in 19 and nine patients 6 months or more after operation. Nine of ten patients with complete splenic vein occlusion developed a collateral circulation in the late postoperative phase. Splenic perfusion was well preserved in all patients.ConclusionSplenic vessel-preserving laparoscopic SPDP has the short-term benefit of good perfusion to the spleen. In the long term, there is a risk of left-sided portal hypertension if the splenic vein becomes occluded after surgery.

Background Mesenchymal stromal cells (MSC) comprise one of the BM stromal cells that are known to support hematopoiesis. It has also been suggested recently that MSC display immunosuppressive capacities through inhibiting the differentiation of monocyte-derived DC. DC travel to the lymph nodes (LN) to present Ag to T cells, and CCL21 is the chemokine that plays an important role in DC migration into the T-cell area of LN. We addressed the effect of MSC on this chemotactic activity of DC, one of the typical characteristics upon maturation. Methods BM cells were isolated and then cultured for generation of myeloid DC in the presence of GM-CSF and/or lipopolysaccharide with or without MSC. MSC were identified by flow cytometry of the immunologic markers and by performing colony-forming unit fibroblast assay. Migration of DC was observed with a newly developed time-lapse video microscopic technique. Results MSC co-culture inhibited the initial differentiation of DC, as well as their maturation. The matured DC actively migrated directionally in response to CCL21, a powerful DC-attracting chemokine, whereas the MSC co-cultured DC did not. Discussion Collectively, the findings of these experiments raise the possibility that MSC suppress the migratory function of DC and so they may serve immunoregulatory activities through the modulation of the Ag-presenting function of DC.

One of the peculiar features of Plasmodium vivax malaria in South Korea is the surprisingly high frequency of thrombocytopenia. The mechanism by which this malaria-related thrombocytopenia develops and its role in the pathology and progress of human infection with P. vivax have not yet been completely understood. In the present study, the serum cytokine profiles of cases of P. vivax malaria who presented with thrombocytopenia were compared with those of similar cases who did not have thrombocytopenia at presentation. The subjects were the 94 consecutive cases of P. vivax malaria who presented at five hospitals in South Korea (all near the Demilitarized Zone) between May 2000 and October 2002, 47 of whom had thrombocytopenia at presentation. When mean values and (S.E.) were compared, the thrombocytopenic patients were found not only to be generally older than the non-thrombocytopenic [25.3 (1.1) v. 21.3 (0.18) years; P0.001] but also to have presented with higher serum concentrations of aspartate aminotransferase [77.6 (16.6) v. 32.3 (7.4) U/litre; P0.0001], alanine aminotransferase [96.7 (19.0) v. 44.7 (12.0) U/litre; P = 0.0001], interleukin-1 [49.9 (7.4) v. 23.7 (5.1) pg/ml; P0.001], interleukin-6 [174.9 (26.4) v. 57.3 (14.6) pg/ml; P = 0.001], interleukin-10 [308.2 (39.6) v. 137.9 (23.1) pg/ml; P0.002] and transforming growth factor-beta [1134.3 (387.5) v. 416.6 (183.8) pg/ml; P0.0001], and higher levels of parasitaemia [4345.7 (966.6) v. 1443.8 (222.7) parasites/microl; P = 0.03). The non-thrombocytopenic patients, however, had relatively high total leucocyte counts [5.8 (0.24) v. 5.4 (0.66) leucocytes/nl; P = 0.03]. The thrombocytopenia associated with P. vivax malaria in South Korea therefore appears to be associated with elevated serum concentrations of both pro- and anti-inflammatory cytokines. To define the role of each cytokine in the development of thrombocytopenia during the course of acute P. vivax malaria, further prospective studies are needed.

The objective of this study was to evaluate the results of laser in situ keratomileusis (LASIK) for high myopia after a follow-up of two years. A total of 42 eyes from 33 patients with high myopia (range: -9.00 D to -25.50 D) were studied. LASIK was performed using an automated microkeratome (Steinway, USA) and OmniMed II excimer laser with the standard MKM program (Summit Technology, Inc., Waltham, MA) in all patients. The patients were followed up at one, three, six, 12 and 24 months. During follow-up manifest refraction and best corrected and uncorrected visual acuity were measured. Any complications were also analyzed. The two-year follow-up results were as follows. The mean postoperative manifest spherical equivalents (MSE) were -0.51 D at one month, -1.09 D at three months, -1.78 D at six months, -2.17 D at 12 months and -2.61 D at 24 months. Myopic regression continued during the two-year follow-up (p < 0.05). The accuracy of the intended postoperative correction within +/- 2.00 D was 73.8% at one month, 69.1% at three months, 52.4% at six months, 52.4% at 12 months, and 45.2% at 24 months. The best corrected visual acuity (BCVA) was unchanged or increased in 35 eyes (83.3%). Only three eyes (7.2%) lost two or more lines of BCVA. This was due to irregular astigmatism in one eye, macular degeneration in one eye, and rhegmatogenous retinal detachment in one eye. In this study, LASIK was effective and safe in the correction of high myopia, however continuous myopic regression was seen over the two-year follow-up. Refining the nomogram to adjust for progressive myopic regression will be necessary in order to obtain better results.

Insulin-dependent diabetes mellitus (IDDM), also known as type 1 diabetes, results from the destruction of pancreatic β cells (27, 31). Genetic and environmental factors are believed to be involved in the pathogenesis of IDDM (24, 25, 30). Viral infection is one environmental factor considered to play a role in this disease. Among the viruses implicated in the development of IDDM, the most clear and unequivocal evidence that a virus induces the disease comes from studies on the D variant of encephalomyocarditis (EMC) virus (EMC-D virus) in mice (7, 34) and Kilham rat virus in rats (6, 11). In genetically susceptible strains of mice, EMC-D virus causes diabetes by the selective destruction of β cells. The molecular identification of the EMC virus genes responsible for the induction of diabetes (16, 17, 29) and the genetic factors of the host (19, 32) have been extensively studied. However, the molecular immune mechanisms involved in the pathogenesis of diabetes in EMC virus-infected mice remain to be determined. Earlier studies showed that the selective infection of pancreatic β cells with EMC-D virus leads to the recruitment of macrophages into the islets followed by infiltration of T lymphocytes (1). Depletion of macrophages prior to infection of mice with a low dose of EMC-D virus resulted in the prevention of diabetes (2, 14). In contrast, the incidence of diabetes increased when macrophages were activated prior to viral infection (2). The depletion of T lymphocytes failed to alter the incidence of diabetes in EMC-D virus-infected mice (33). These results indicate that macrophages play a primary role in the destruction of β cells in mice infected with a low dose of EMC-D virus. Our recent study showed that macrophages activated by EMC-D virus in vivo produce the soluble mediators interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and inducible nitric oxide synthase (iNOS), which play an important role in the destruction of β cells (12). However, the mechanisms that activate macrophages are not known. This investigation was initiated to determine whether a tyrosine kinase signal pathway might be involved in the EMC-D virus-induced activation of macrophages in vitro and, if so, whether the administration of a tyrosine kinase inhibitor in vivo might protect against EMC-D virus-induced diabetes. For our study, we focused on the tyrosine kinase inhibitors tyrphostin AG126 and tyrphostin AG556 (hereafter referred to simply as AG126 and AG556), which have been shown to prevent lipopolysaccharide (LPS)-induced lethal toxicity either in mice (23) or dogs (28), respectively. We now report that AG126 prevents EMC-D virus-mediated macrophage activation in vitro. Further, when administered in vivo prior to infection of DBA/2 mice with EMC-D virus, AG126 led to a reduction of β-cell destruction and a reduction in the incidence of diabetes. This result suggests that a tyrosine kinase signalling pathway involved in the EMC-D virus-induced activation of macrophages plays a role in macrophage-dependent β-cell destruction, leading to the development of diabetes in mice.

A 24-year-old healthy male underwent uncomplicated laser in situ keratomileusis (LASIK) in left eye. One day after the surgery, he complained of ocular pain and multiple corneal stromal infiltrates had developed in left eye. Immediately, the corneal interface and stromal bed were cleared, and maximal antibiotic treatments with fortified tobramycin (1.2%) and cefazolin (5%) were given topically. The causative organism was identified as 'Streptococcus viridans' both on smear and culture. Two days after antibiotic therapy was initiated, the ocular inflammation and corneal infiltrates had regressed and ocular pain was relieved. One month later, the patient's best corrected visual acuity had returned to 20/20 with -0.75 -1.00 x 10 degrees, however minimal stromal scarring still remained. This case demonstrates that microbial keratitis after LASIK, if treated promptly, does not lead to a permanent reduction in visual acuity.

Background We previously found that GADD45b, which is associated with cellular stress response and apoptosis regulation, contributes to sorafenib resistance in HCC cells. The present study explored the role of GADD45γ, another GADD45 family protein, in HCC treatment. Methods HCC cell lines tested included Huh-7, HepG2, Hep3B, Huh-7R, HepG2R, the latter two sorafenib-resistant cell lines established by continuously exposure of Huh-7 and HepG2 cells to sorafenib. GADD45γ expression was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Control of GADD45γ transcription was examined by luciferase reporter assay using a series of reporter plasmids with deletions or site-directed mutants of the 5′-flanking region of GADD45γ promoter. Apoptosis was analyzed by flow cytometry and western blotting. Expression of GADD45γ in human HCC tumor tissues was measured by qRT-PCR and immunohistochemistry. Results GADD45γ mRNA and protein levels were increased after sorafenib independent of cellular MEK/ERK activity. GADD45γ induction was more prominent in sorafenib-sensitive HCC cells (Huh-7 and HepG2, IC50 6-7 µM) than in sorafenib-resistant HCC cells (Hep3B, Huh-7R and HepG2R, IC50 12-15 µM). Knockdown of GADD45γ expression partially abrogated the pro-apoptotic effects of sorafenib in sorafenib-sensitive cells but not sorafenib-resistant cells. The region -449/ - 82 in the 5′-flanking region of GADD45γ promoter was found crucial for GADD45 gamma induction by sorafenib. Decreased GADD45γ expression in HCC tumor tissue was associated with worse overall survival in patients who underwent surgery for HCC. Conclusions Induction of GADD45γ expression contributes to sorafenib-induced apoptosis in HCC cells. The role of GADD45γ as a predictive biomarker for sorafenib sensitivity in HCC warrants further exploration. (Supported by grants NSC-100-2325-B-002 -042, NSC 100-2314-B-002 -058-MY3, DOH100-TD-B-111-001, and NHRI-EX101-9911BC.)

Background PI3K/AKT/mTOR pathway upregulation has been implicated in T resistance, and thus the impact of pathway inhibition on restoration of therapeutic sensitivity is being investigated. The RP2D of BKM120, an oral pan-class I PI3K inhibitor, plus T is 100 mg/d. Here, we present Ph II results of BKM120 + T in pts with T-resistant advanced HER2+ BC. Methods Pts with HER2+ locally adv/metastatic BC resistant to T (progression while on T, or within 4 wks [metastatic] or 12 mths [adjuvant] of last T dose) received daily BKM120 (100 mg) and the standard wkly dose of T. Ph II eligibility criteria: ≥1 measurable lesion, ≥1 but ≤4 prior anti-HER2 regimens (incl. trastuzumab [required], lapatinib, and/or T-DM1), and ≤3 lines of prior chemotherapy for metastatic disease. Ph IB pts treated at the RP2D who met Ph II eligibility criteria were included in the analysis. Results As of 23 March 2012, 53 pts were included in the Ph II analysis (safety set; incl. 8 pts from Ph IB). 49 pts were evaluable for response (full analysis set); median age 52 yrs (28–75); median no. prior antineoplastic regimens 4 (1–10); 5 pts had a baseline CNS lesion (3 measurable target; 2 non-target). At data cut-off, 9 pts were still on study. Most pts discontinued treatment due to disease progression (55%); 8 pts (16%) withdrew due to AEs. Mean duration of BKM120 exposure was 11 wks (0.1–41). Most common suspected study-drug related G3/4 AEs: ALT increased (5 pts); rash (5 pts); AST increased (4 pts); asthenia (3 pts); nausea, anxiety, skin photosensitivity, hyperglycemia (2 pts each). Partial responses (RECIST) were seen in 4 pts (8%), and stable disease (SD) was noted in 20 pts (41%); the disease control rate (CR, PR, or SD) was 49%. Preliminary results indicate that, of the 5 pts with baseline brain mets (BM), 2 pts had SD in the CNS without evidence of progression at study withdrawal; 2 pts had overall SD (1 for 90 days and 1 for 106 days) before progression in the CNS; 1 pt was not evaluated in the CNS after study entry. Conclusion BKM120 in combination with T has an acceptable safety profile, and has shown encouraging preliminary activity in heavily pretreated HER2+ metastatic BC pts with T resistance, including pts with BM. Disclosure Q. Ru: Employee of Novartis. S. Ruquet: Employee of Novartis. D.W. Sternberg: Employee of Novartis. All other authors have declared no conflicts of interest.

4094 Background: Despite potentially curative resection for pancreatic carcinoma the 5-year survival in these patients is less than 20%. Progression of disease can occur both locally and in distant...

Purpose: Nutritional risk screening has been emphasized to predict those patients who are malnourished or at high nutritional risk. In 2006, we developed the Seoul National University Bundang Hospital Nutrition Screening Tool (SNUBHNST) using a nutritional screening index (NSI) based on the predictors of the nutritional status. The aim of this study was to compare the SNUBH-NST and the Nutritional Risk Screening 2002 (NRS 2002) recommended by the European Society for Parenteral and Enteral Nutrition (ESPEN) as the preferred nutritional risk screening tool for hospitalized patients. Methods: Three hundred and eighty two patients hospitalized in medical and surgical wards were screened and classified as being well nourished or at nutritional risk by the SNUBH-NST and the NRS 2002 within 48 h of admission. The anthropometric measurements and laboratory data were assessed and the length of hospital stay was obtained from the medical chart. Differences between independent groups were assessed with Student's t test and the agreement between both tools was analyzed by the χ-test. Spearman's rank correlation coefficients were calculated for the correlation between the nutritional risk and the variables. Results: The SNUBH-NST and the NRS 2002 identified 14.7% and 20.9% of all the assessed patients as being at nutritional risk, respectively, and agreement was observed for 340 of the 382 (89%) patients with using both tools (κ=0.627, P