Investigation of cell signalings and therapeutic targets in PTPRK-RSPO3 fusion-positive colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. MATERIALS AND METHOD: The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. RESULTS: 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways.

Nanomicelle-generating Microneedles Loaded With Tranilast for Treatment of Hypertrophic Scars in a Rabbit Model.

BACKGROUND/AIM: Hypertrophic scars (HS) are the result of pathological wound healing characterized by a red, raised scar formation. The goal of this research was development of a new method for treatment of HS formation. MATERIALS AND METHODS: A tranilast-loaded microneedle (TMN) was developed and applied in a rabbit ear model to treat an induced HS. Scar elevation index, the thickness of dorsal skin by hematoxylin and eosin staining, collagen deposition by Masson trichrome staining and expression of myofibroblast biomarker proteins were evaluated. RESULTS: The 12×12 array of the TMN containing 2.9 µg tranilast per needle released more than 80% of the drug within 30 min. During the procedure, control, non-loaded MN and TMN loaded with three different doses of tranilast (low: 2.5-3, medium: 25-30, and high: 100-150 µg) were applied to the HS in rabbit ears. High-level TMN led to a clear and natural appearance of skin, a decrease in scar elevation index by 47% and decline in the thickness of the epidermis from 69.27 to 15.92 µm when compared to the control group. Moreover, the collagen density also decreased in groups treated with medium- or high-level TMNs, by 10.2% and 9.06%, respectively. Furthermore, the expression of transforming growth factor-ß, collagen-1, and α-smooth muscle actin proteins was reduced in TMN-treated HSs compared to the control. CONCLUSION: The findings show the overall efficacy of TMNs in inhibiting HS. Thus, use of TMN is a simple and cosmetic remedy for HS, with good protection and reliability.

Elucidation of Novel Therapeutic Targets for Breast Cancer with ESR1-CCDC170 Fusion.

Among the various types of breast cancer, the luminal B subtype is the most common in young women, and ESR1-CCDC170 (E:C) fusion is the most frequent oncogenic fusion driver of the luminal B subtype. Nevertheless, treatments targeting E:C fusion has not been well established yet. Hence, the aim of this study is to investigate potential therapies targeting E:C fusion based on systematic bioinformatical analysis of the Cancer Genome Atlas (TCGA) data. One thousand related genes were extracted using transcriptome analysis, and major signaling pathways associated with breast cancer were identified with over-representation analysis. Then, we conducted drug-target network analysis based on the OncoKB and CIViC databases, and finally selected potentially applicable drug candidates. Six major cancer-related signaling pathways (p53, ATR/ATM, FOXM1, hedgehog, cell cycle, and Aurora B) were significantly altered in E:C fusion-positive cases of breast cancer. Further investigation revealed that nine genes (AURKB, HDAC2, PLK1, CENPA, CHEK1, CHEK2, RB1, CCNA2, and MDM2) in coordination with E:C fusion were found to be common denominators in three or more of these pathways, thereby making them promising gene biomarkers for target therapy. Among the 21 putative actionable drugs inferred by drug-target network analysis, palbociclib, alpelisib, ribociclib, dexamethasone, checkpoint kinase inhibitor AXD 7762, irinotecan, milademetan tosylate, R05045337, cisplatin, prexasertib, and olaparib were considered promising drug candidates targeting genes involved in at least two E:C fusion-related pathways.

Real-time visualization of two-photon fluorescence lifetime imaging microscopy using a wavelength-tunable femtosecond pulsed laser.

A fluorescence lifetime imaging microscopy (FLIM) integrated with two-photon excitation technique was developed. A wavelength-tunable femtosecond pulsed laser with nominal pulse repetition rate of 76-MHz was used to acquire FLIM images with a high pixel rate of 3.91 MHz by processing the pulsed two-photon fluorescence signal. Analog mean-delay (AMD) method was adopted to accelerate the lifetime measurement process and to visualize lifetime map in real-time. As a result, rapid tomographic visualization of both structural and chemical properties of the tissues was possible with longer depth penetration and lower photo-damage compared to the conventional single-photon FLIM techniques.

High-speed time-resolved laser-scanning microscopy using the line-to-pixel referencing method.

Fluorescence lifetime imaging microscopy (FLIM) is a powerful technique to visualize photophysical characteristics of biological targets. However, conventional FLIM methods have some limitations that restrict obtaining high-precision images in real time. Here, we propose a high-speed time-resolved laser-scanning microscopy by incorporating a novel line-to-pixel referencing method into the previously suggested analog mean-delay (AMD) method. The AMD method dramatically enhances the photon accumulation speed for achieving the certain precision compared to the time-correlated single-photon counting (TCSPC) method while maintaining high photon efficiency. However, its imaging pixel rate can still be restricted by the rearm time of the digitizer when it is triggered by laser pulses. With our line-to-pixel referencing method, the pulse train repeats faster than the trigger rearm time can be utilized by generating a line trigger, which is phase-locked with only the first pulse in each horizontal line composing an image. Our proposed method has been tested with a pulsed laser with 40 MHz repetition rate and a commercial digitizer with a 500 ns trigger rearm time, and a frame rate of 3.73 fps with a pixel rate of 3.91 MHz was accomplished while maintaining the measurement precision under 20 ps.

Comparison of results of medial opening-wedge high tibial osteotomy with and without subchondral drilling.

PURPOSE: The purposes of this study were to compare the results of medial opening-wedge high tibial osteotomy (MOWHTO) with and without subchondral drilling and to assess the formation of fibrocartilage at 2 years postoperatively. METHODS: Patients were divided into 2 groups. Thirty knees were treated with osteotomy and subchondral drilling (group 1), and 31 knees were treated with osteotomy alone (group 2). Clinical evaluations were performed by use of Knee Society scores preoperatively and at 2 years postoperatively. For evaluation of cartilage degeneration, the International Cartilage Repair Society grading system was used for arthroscopic grading on initial arthroscopy during high tibial osteotomy. The patients underwent a second-look arthroscopic evaluation of the articular cartilage at the time of removal of the plate, an average of 2 years after the initial osteotomy. For evaluation of formation of fibrocartilage on second-look arthroscopy, the articular cartilage was classified as having either no change from initial surgery (grade I) or white scattering with fibrocartilage, partial coverage with fibrocartilage, or even coverage with fibrocartilage (grade II). In addition, maturation of the appearance of the cartilage was defined. The appearance was considered mature if the chondral defects were evenly covered with fibrocartilage. It was considered immature if there was white scattering or only partial coverage with fibrocartilage. RESULTS: In group 1 the mean Knee Society knee score and function score were 67.3 ± 8.2 points and 66.5 ± 14.3 points, respectively, preoperatively. At 2 years postoperatively, they improved to 91.2 ± 6.4 and 92.8 ± 10.0, respectively (P = .001 and P = .001, respectively). In group 2 the mean Knee Society knee score and function score were 63.7 ± 13.9 points and 66.8 ± 9.1 points, respectively, preoperatively. At 2 years postoperatively, they improved to 92.5 ± 5.3 points and 92.2 ± 8.0 points, respectively (P = .001 and P = .001, respectively). There were no significant differences in the postoperative Knee Society knee score and function score at 2 years' follow-up between the groups (P = .389 and P = .806, respectively). Grade II regeneration was achieved in the medial femoral condyle articular cartilage in 100% of knees in group 1 and 94% of knees in group 2 (P = .492). Maturation of the cartilage was found in the medial femoral condyle articular cartilage in 10% of knees in group 1 and 3% of knees in group 2 (P = .354). There was no significant difference in the formation of fibrocartilage between the groups. CONCLUSIONS: Subchondral drilling had no effect on the outcome at 2 years after MOWHTO. In addition, there was no significant difference in the formation of fibrocartilage with or without subchondral drilling. Therefore subchondral drilling is not necessary after MOWHTO. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Efficacy of periarticular multimodal drug injection after medial opening-wedge high tibial osteotomy: a randomized, controlled study.

PURPOSE: The purpose of this study was to evaluate the efficacy of periarticular multimodal drug injection after medial opening-wedge high tibial osteotomy regarding the postoperative pain level. METHODS: From January 2011 to January 2012, 70 patients underwent medial opening-wedge high tibial osteotomy. Thirty-five patients were randomly assigned to receive no injection (group I), and 35 patients were assigned to receive periarticular multimodal drug injection (group II). These 2 groups were compared regarding the postoperative pain level, frequency of additional nonsteroidal anti-inflammatory drug injections, total amount of patient-controlled analgesia, and number of times that patients pushed the patient-controlled analgesia button at each time interval. Statistical results were based on multivariate analysis of variance and repeated-measures analyses. RESULTS: Multivariate analysis of variance of mean visual analog scale (VAS) scores over the 2-week postoperative period showed statistical significance (P < .001). Repeated-measures analysis yielded a statistically significant difference (P = .001) for the time-by-treatment interaction, showing a clear periarticular multimodal drug injection benefit over time based on VAS scores. In addition, the mean number of times that patients pushed the patient-controlled analgesia button differed significantly between groups over time (P = .01). The VAS scores, frequency of additional nonsteroidal anti-inflammatory drug injections, mean number of times that patients pushed the patient-controlled analgesia button, and mean total amount of fentanyl consumption differed significantly within each group over time (P < .001 for all variables). However, the frequency of additional nonsteroidal anti-inflammatory drug injections and mean total amount of fentanyl consumption did not differ significantly between groups over time (P = .822, P = .529, and P = .282). Opioid- and injection-related complications were not found. CONCLUSIONS: This prospective randomized study shows that intraoperative periarticular multimodal drug injections in patients undergoing medial opening-wedge high tibial osteotomy for unicompartmental osteoarthritis of the knee could result in significant reductions in VAS scores at 2 weeks postoperatively. LEVEL OF EVIDENCE: Level I, high-quality randomized controlled trial with statistically significant differences.

Labrenzia suaedae sp. nov., a marine bacterium isolated from a halophyte, and emended description of the genus Labrenzia.

An endophytic, Gram-staining-negative bacterium was isolated from sterilized roots of a plant, Suaeda maritima, growing on tidal flats. Cells of the strain were motile by means of a single polar flagellum and colonies were pigmented light brown. Strain YC6927(T) was able to grow at 15-37 °C (optimum at 28-30 °C) and at pH 5.0-10.0 (optimum at pH 7.0-8.0). The strain was able to grow at NaCl concentrations of 0-9.0 % (w/v), with optimum growth at 0-5.0 % NaCl. Comparison of 16S rRNA gene sequences showed that the strain was a member of the genus Labrenzia, exhibiting the highest similarity to Labrenzia marina mano18(T) (97.6 % sequence similarity). Strain YC6927(T) produced light-brown carotenoid pigments. The major respiratory quinone was Q-10 and the DNA G+C content was 58.5 mol%. The DNA-DNA relatedness between strain YC6927(T) and closely related strains was between 8.2±1.8 and 20.3±1.5 %. Strain YC6927(T) contained summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C14 : 0 3-OH as major fatty acids, confirming the affiliation of the strain with the genus Labrenzia. The polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylmonomethylethanolamine, an unknown aminolipid, an unknown phospholipid and five unknown lipids. On the basis of phylogenetic analysis, physiological and biochemical characterization and DNA-DNA hybridization data, strain YC6927(T) should be assigned to a novel species of the genus Labrenzia, for which the name Labrenzia suaedae sp. nov. is proposed. The type strain is YC6927(T) ( = KACC 13772(T) = DSM 22153(T)). An emended description of the genus Labrenzia is also proposed.

Second-look arthroscopic assessment of cartilage regeneration after medial opening-wedge high tibial osteotomy.

PURPOSE: The purposes of this study were to evaluate regeneration of the articular cartilage after medial opening-wedge high tibial osteotomy for knees with medial-compartment osteoarthritis and to assess the clinical outcome and cartilage regeneration according to the postoperative limb alignment at 2 years postoperatively. METHODS: The study involved 159 knees in 159 patients. For evaluation of cartilage degeneration, the International Cartilage Repair Society grading system was used for arthroscopic grading on initial arthroscopy during high tibial osteotomy. The patients underwent a second-look arthroscopic evaluation of the articular cartilage at the time of removal of the plate, an average of 2 years after the initial osteotomy. For evaluation of cartilage regeneration, the articular cartilage was classified into 2 stages as no regenerative change (grade 1) or white scattering with fibrocartilage, partial coverage with fibrocartilage, or even coverage with fibrocartilage (grade 2) on second-look arthroscopy. Maturation of the cartilage regeneration was defined as even coverage with fibrocartilage. "Immaturation" of the cartilage regeneration was defined as white scattering with fibrocartilage or partial coverage with fibrocartilage. Clinical evaluations were performed by use of Knee Society scores preoperatively and at 2 years postoperatively. We divided the knees into 3 groups according to the postoperative limb alignment. Group A comprised knees with a mechanical tibiofemoral angle of 0° or less. Group B comprised knees with a mechanical tibiofemoral angle greater than 0° and less than 6°. Group C comprised knees with a mechanical tibiofemoral angle of 6° or greater. RESULTS: Grade 2 regeneration was achieved in the medial femoral condyle articular cartilage in 92% of knees and in the medial tibial plateau articular cartilage in 69% of knees. Maturation of the cartilage regeneration was found in the medial femoral condyle articular cartilage in 4% of knees and in the medial tibial plateau articular cartilage in 1% of knees. At follow-up, no significant differences were seen between clinical outcomes and initial cartilage degeneration (P = .338) or cartilage regeneration (P = .699). Regeneration of the medial femoral condyle articular cartilage was found in 75% of group A knees, 95% of group B knees, and 92% of group C knees. Significant differences were seen between cartilage regeneration and clinical outcomes (P = .001), as well as postoperative limb alignment (P = .018). Clinical and regeneration results were better in group B than in groups A and C. CONCLUSIONS: The degenerated cartilage of the medial femoral condyle and medial tibial plateau could be partially or entirely covered by newly regenerated cartilage at 2 years after adequate correction of varus deformity by medial opening-wedge high tibial osteotomy without cartilage regeneration strategies. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Transglutaminase 2 expression predicts progression free survival in non-small cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitor.

Transglutaminase 2 (TG2), a cross-linking enzyme, is involved in drug resistance and in the constitutive activation of nuclear factor kappa B (NF-κB). We investigated the association of non-small cell lung cancer (NSCLC) treatment efficacy with TG2 and NF-κB expression in 120 patients: 102 with adenocarcinoma and 18 with other histologic types. All patients underwent surgery; 88 received adjuvant chemotherapy, with 28 receiving platinum-based doublet chemotherapy as first-line treatment and 29 receiving epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy. Patients' TG2 and NF-κB expression values were calculated semiquantitatively. The median TG2 value was 50 (range, 0-300) and the median NF-κB value was 20 (range, 0-240). Disease-free survival did not differ between the low- and high-TG2 groups. Among patients who received palliative platinum-based doublet chemotherapy, progression free survival (PFS) was longer in the low-TG2 group than in the high-TG2 group (11.0 vs. 7.0 months; P=0.330). Among those who received EGFR-TKI therapy, PFS was also longer in the low-TG2 group than in the high-TG 2 group (11.0 vs. 2.0 months; P=0.013). Similarly, in EGFR wild-type patients treated with EGFR-TKI, PFS was longer in patients with low TG2 expression (9.0 vs. 2.0 months; P=0.013). TG2 expression levels can predict PFS in patients with NSCLC treated with EGFR-TKI.

Amorphus suaedae sp. nov., isolated from the root of a tidal flat plant, Suaeda maritima.

A novel bacterial strain, YC6899(T), was isolated from the root of Suaedae maritima growing on a tidal flat of Namhae Island, Korea. Cells were Gram-reaction-negative, rod-shaped, non-motile, slightly halophilic and heterotrophic. Strain YC6899(T) grew optimally at a salinity of 2-4 %, at 25-37 °C and at pH 6.5-8.0. Phylogenetic analysis of 16S rRNA gene sequences demonstrated that strain YC6899(T) was closely related to Amorphus orientalis YIM D10(T) (96.1 % similarity) and Amorphus coralli RS.Sph.026(T) (95.9 %). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unknown aminolipids, an unknown aminophospholipid, an unknown aminoglycolipid, unknown glycolipids and unknown lipids. The major fatty acids of strain YC6899(T) were C19 : 0 cyclo ω8c and C18 : 1ω7c. The G+C content of the genomic DNA was 61.3 mol%. Strain YC6899(T) contained ubiquinone-10 (Q-10) as the major respiratory quinone system. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain YC6899(T) represents a novel species within the genus Amorphus, for which the name Amorphus suaedae sp. nov. is proposed. The type strain is YC6899(T) ( = KACC 14912(T) = NBRC 107845(T)).

Comparative study of medial opening-wedge high tibial osteotomy using 2 different implants.

PURPOSE: The purpose of this study was to perform a retrospective clinical and radiographic evaluation after opening-wedge high tibial osteotomy (HTO) using a short spacer plate (Aescula; B. Braun Korea, Seoul, South Korea) and rigid long plate (TomoFix plate; Mathys, Bettlach, Switzerland) at follow-up 2 years postoperatively. METHODS: We performed 94 opening-wedge HTOs with the Aescula plate (group I) and 92 HTOs with the TomoFix plate (group II). Patients underwent clinical and radiographic evaluations preoperatively and at 2 years postoperatively. Clinical evaluations were performed with Knee Society scores. Radiographic analysis included the mechanical tibiofemoral angle (mTFA) and the slope of the tibia angle with preoperative and postoperative full weight-bearing anteroposterior whole-leg views, as well as anteroposterior, lateral, and Merchant views of the knee. We measured the mTFA. In addition, we evaluated the complications in each group. The follow-up period was 2 years. RESULTS: At follow-up 2 years postoperatively, we observed an overall complication rate of 38% in group I and 26% in group II (P = .083). We found plate-related complication rates of 20% in group I and 9% in group II (P = .039). Plate-related complications included loss of correction, fracture of the tibial plateau, screw failure, malunion, and fracture of the lateral cortical bone. The mean mTFA was -6.0° ± 3.2° in group I and -4.6° ± 2.8° in group II preoperatively (P = .262). The mean mTFA was 1.0° ± 3.1° in group I and 1.5° ± 2.3° in group II at the latest follow-up (P = .034). In group I, the mean Knee Society knee score and function score were 60.0 ± 12.9 and 57.9 ± 26.8, respectively, preoperatively. They improved to 92.1 ± 8.1 and 89.0 ± 15.1, respectively, at follow-up (P = .001 and P = .001, respectively). In group II, the mean Knee Society knee score and function score were 57.5 ± 14.8 and 57.4 ± 22.1, respectively, preoperatively. They improved to 95.5 ± 5.4 and 95.0 ± 7.6, respectively, at follow-up (P = .001 and P = .001, respectively). In addition, the mean postoperative knee score and function score in group II were higher than those in group I (P = .001 and P = .001, respectively). CONCLUSIONS: We have shown a high plate-related complication rate and a significant loss of correction during a short-term follow-up period (2 years) after opening-wedge HTO using the new short spacer HTO plate compared with the rigid long plate. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

A phase I trial of gefitinib and nimotuzumab in patients with advanced non-small cell lung cancer (NSCLC).

BACKGROUND: Nimotuzumab (TheraCIM®) is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with minimal skin toxicity. Combining a different class of anti-EGFR drug with gefitinib is a new strategy to overcome intrinsic and acquired resistance to gefitinib. The aim of this phase I trial was to determine recommended phase II dose (RPIID) and the safety of gefitinib and nimotuzumab combination treatment. METHODS: Patients with advanced/metastatic NSCLC were treated with escalating doses of weekly nimotuzumab (100mg or 200mg, IV) and fixed doses of daily gefitinib (250 mg/day, PO) until disease progression or unacceptable toxicity. We planned to enroll 10 additional patients at RPIID to ascertain the safety of treatment. EGFR mutations and KRAS mutations were analyzed from available tumor samples. RESULTS: A total of 16 patients were enrolled (3 in 100mg cohort, 13 in 200mg cohort). Six patients (37.5%) were female, and 5 (31.3%) were never smokers. Adenocarcinoma was the major histologic type (13 patients, 81.3%). Treatment was well-tolerated without dose-limiting toxicity (DLT). Four patients (25.0%) experienced grade 2 skin toxicity (1 in 100mg cohorts, 3 in 200mg cohort). Other common grade 1/2 toxicities were fatigue (37.5%) and diarrhea (25.0%). Among 16 evaluable patients, four patients (25.0%) achieved partial response and 7 patients (43.8%) had stable disease. Two of 4 responders had EGFR mutation (exon 19 deletion). CONCLUSIONS: Dual agent molecular targeting of EGFR with nimotuzumab and gefitinib in patients with advanced NSCLC is well-tolerated. The RPIID for nimotuzumab is 200mg weekly IV and for gefitinib 250 mg/day PO. Based upon this phase I trial, we are planning to conduct a randomized phase II trial comparing gefitinib and nimotuzumab with gefitinib alone in patients with advanced NSCLC.

No difference in total blood loss, haemoglobin and haematocrit between continues and intermittent wound drainage after total knee arthroplasty.

PURPOSE: The purpose of this prospective randomized study was to compare the visible, hidden, total blood loss and postoperative haemodynamic change of 4-h clamping and nonclamping of the drain after TKA. The hypothesis in the present study was that intermittent drain clamping with injection of diluted epinephrine solution would decrease the visible, hidden blood loss and reduction of postoperative haemoglobin or haematocrit change after TKA. METHODS: From January 2010 to January 2011, 100 TKAs were performed at our hospital. In group I (50 knees), drainage was clamped for the first 4 postoperative hours with injection of diluted epinephrine solution. In group II (50 knees), drainage was not clamped without injection of diluted epinephrine solution. Two drains with an external diameter of 3.2 mm were inserted into the knee joint. We checked the amount of drainage recorded at 6, 12, 24, and 48 h postoperatively. Also, we checked the haemoglobin and haematocrit on the preoperation, first, 5th and 10th postoperative days. We analysed the transfusion rate, the possible adverse issues with clamping drainage, and the range of motion of the knee. RESULTS: The mean total bloody drainage was significantly less in group I than group II (560.7 ± 249.9 mL vs 978.3 ± 327.5 mL) (p < 0.001). The decrease of haemoglobin and haematocrit after surgery was not significant between the two groups (n.s.). The hidden blood loss was significantly more in group I than group II (541.1 ± 439.4 mL vs 32.1 ± 21.9 mL) (p < 0.001). So, total blood loss showed no significant difference between the two groups (1,101.8 ± 373.6 mL vs 1,010.4 ± 385.9 mL) (n.s.). The postoperative range of motion and transfusion rate between the two groups were not significant (n.s.). But immediate wound problem, such as oozing, was significantly more in group I (p < 0.001). CONCLUSION: It is not necessary to perform the intermittent drain clamping with injection of the diluted epinephrine solution in TKA because there is no impact on the postoperative haemoglobin and haematocrit. If anything, the intermittent drain clamping with injection of the diluted epinephrine solution increased the hidden blood loss and immediate wound problem than nonclamping without injection of the diluted epinephrine solution.

The accuracy of the extramedullary and intramedullary femoral alignment system in total knee arthroplasty for varus osteoarthritic knee.

PURPOSE: The intramedullary (IM) femoral alignment system does not alway guarantee accuracy of the component position in the total knee arthroplasty (TKA). In some cases, the extramedullary (EM) femoral alignment system in total knee arthroplasty (TKA) is a useful alternative surgical option to adjust femoral component alignment. In the EM technique, accuracy of the femoral head center location is mandatory. The purpose of this prospective randomized study was to compare the alignment after TKA using two different femoral alignment systems. METHODS: From January 2009 to December 2009, 91 patients (106 knees) with osteoarthritis underwent TKA. The IM femoral alignment system was used in 50 TKAs, and the EM system was used in 56 TKAs. We measured the coronal, sagittal alignment of the femoral component, and overall alignment from full-length standing. Anteroposterior radiographs were taken 1 year after surgery. RESULTS: The overall limb alignment was 0.2° ± 1.9° varus in the EM group and 1.1° ± 1.9° valgus in the IM group (p = 0.001). The coronal alignment of the femoral component was 90.0° ± 1.1° in the EM group and 90.3° ± 1.2° in the IM group, not statistically different (n.s.). The sagittal alignment of the femoral component was 2.3° ± 1.7° in the EM group and 2.5° ± 1.0° in the IM group (n.s.). Clinically acceptable overall limb alignment was achieved in 91.1 % of EM group and 84.0 % of IM group (n.s.). CONCLUSION: The present study suggests that by applying our EM technique that uses a newly designed mechanical axis marker system, the alignment of the femoral component and overall limb alignment is reliable and at least as accurate as the standard IM technique. LEVEL OF EVIDENCE: I.

Comparison of the clinical outcomes after total knee arthroplasty with the LCS rotating platform mobile bearing knee system and the PFC Sigma RP-F mobile bearing knee system.

BACKGROUND: We compared clinical outcomes after total knee arthroplasty with the Low Contact Stress (LCS) rotating platform mobile bearing knee system and the Press Fit Condylar Sigma rotating platform high flexion (PFC Sigma RP-F) mobile bearing knee system. METHODS: Fifty cases of total knee arthroplasty were performed with the PFC Sigma RP-F mobile bearing knee system and sixty-one cases were performed with the LCS mobile bearing total knee arthroplasty. The average duration of follow-up was 2.9 years. RESULTS: The mean Hospital for Special Surgery (HSS) knee score was 62.1 (range, 52 to 75) in the LCS group and 61.9 (range, 50 to 74) in the Sigma RP-F group preoperatively, and 90.1 (range, 84 to 100) in the LCS group and 89.8 (range, 83 to 100) in the Sigma RP-F group at the final follow-up. The mean preoperative flexion contracture was 6.7° (range, 0° to 10°) in the LCS group and 9.3° (range, 0° to 15°) in the Sigma RP-F group preoperatively. The mean range of motion was 124.6° (range, 105° to 150°) in the LCS group and 126.1° (range, 104° to 145°) in the Sigma RP-F group at the final follow-up. CONCLUSIONS: After a minimum duration of follow-up of two years, we found no significant differences between the two groups with regard to the range of knee motion or the clinical or radiographic results.

Comparison of two inflammation-based prognostic scores in patients with unresectable advanced gastric cancer.

OBJECTIVES: The objective of this study was to compare the usefulness of two inflammation-based prognostic scores, neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS), assessed at diagnosis in stage IV advanced gastric cancer (AGC). METHODS: We retrospectively reviewed the medical records of 104 patients with newly diagnosed metastatic AGC treated with palliative chemotherapy. RESULTS: In the univariate analysis, the following variables were associated with shorter overall survival (OS): poor or undifferentiated histology (p = 0.013), more than 1 metastasis (p = 0.004), the presence of lymph node metastasis (p = 0.003), the presence of bone metastasis (p = 0.019), a lower albumin level (p < 0.001), elevated C-reactive protein (p < 0.001), a high absolute neutrophil count (p = 0.016), NLR ≥3 (p < 0.001) and higher mGPS (p < 0.001 and p = 0.007, respectively). In the multivariate analysis, high NLR and mGPS were independent prognostic factors for shorter OS (p = 0.037, p < 0.001 and p = 0.010, respectively), along with lymph node metastasis (p = 0.005) and histological subtype (p = 0.048). CONCLUSION: This study suggests that the inflammatory markers, NLR and mGPS, are independent prognostic factors for OS in patients with unresectable AGC treated with palliative chemotherapy.

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL).

BACKGROUND: The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. METHODS: Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. RESULTS: Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001). CONCLUSIONS: Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.