Kinematic Alignment Achieves a More Balanced Total Knee Arthroplasty Than Mechanical Alignment among CPAK Type I Patients: A Simulation Study.

Background: There is no consensus on whether mechanical alignment (MA) or kinematic alignment (KA) should be chosen for total knee arthroplasty (TKA) for coronal plane alignment of the knee (CPAK) Type I with a varus arithmetic HKA (aHKA) and apex distal joint line obliquity (JLO). The aim of this study was to investigate whether MA or KA is preferable for soft tissue balancing in TKA for this phenotype. Method: This prospective cohort study included 64 knees with CPAK Type I osteoarthritis that had undergone cruciate-retaining TKA. Using optical tracking software, we simulated implant placement in the Mako system before making the actual bone cut and compared the results between MA and KA. Extension balance (the difference between medial and lateral gaps in extension) and medial balance (the difference in medial gaps in flexion and extension) were examined. These gap differences within 2 mm were defined as good balance. Achievement of overall balance was defined as an attainment of good extension and medial balance. The incidence of balance in each patient was compared with an independent sample ratio test. Results: Compared with the MA group, the KA group achieved better soft tissue balance in extension balance (p < 0.001). A total of 75% of the patients in the KA group achieved overall balance, which was greater than the 38% achieved in the MA group (p < 0.001). Conclusions: In robot-assisted TKA for CPAK Type I osteoarthritis, KA achieved knee balance during extension without soft tissue release in a greater percentage of patients than MA.

Distribution of Coronal Plane Alignment of the Knee Classification in Patients with Knee Osteoarthritis in Japan.

Coronal plane alignment of the knee (CPAK) has recently been proposed as a simple and universal classification system to determine the suitability of a particular phenotype of the knee to a specific alignment strategy for knee replacement surgery. Although racial differences may affect knee alignment, there are no reports on the racial distribution of this classification system. We aimed to clarify the distribution of CPAK classification in patients with osteoarthritis who underwent total knee arthroplasty (TKA) in Japan. Consecutive patients who underwent primary TKA were analyzed retrospectively. The knees were categorized according to the CPAK classification system which comprised of two independent variables (arithmetic hip-knee-ankle [aHKA] angle and joint-line obliquity [JLO]) with three respective subgroups to create the following nine phenotypes of the knee: type I (varus aHKA and apex distal JLO), type II (neutral aHKA and apex distal JLO), type III (valgus aHKA and apex distal JLO), type IV (varus aHKA and neutral JLO), type V (neutral aHKA and neutral JLO), and type VI (valgus aHKA and neutral JLO), type VII (varus aHKA and apex proximal), type VIII (neutral aHKA and apex proximal), and type IX (valgus aHKA and apex proximal). The distribution of the phenotypes in the Japanese population was investigated as a primary outcome. To accurately compare the results with previous studies conducted on non-Japanese patients, a sex-matched distribution was investigated as a secondary outcome. A total of 570 knees were investigated of which 500 knees were examined after exclusions. The most common distribution was type I (53.8%), followed by type II (25.4%), type III (8.2%), type IV (7.2%), type V (4.4%), and type VI (1.0%). Types VII, VIII, and IX were not distributed. The sex-matched distribution was nearly identical to the overall distribution in Japan. The majority of patients with knee osteoarthritis in Japan had medially tilted joints with constitutional varus alignment.

Preoperative Magnetic Resonance Imaging as a Diagnostic Aid for Hypermobile Lateral Meniscus.

BACKGROUND: Hypermobile lateral meniscus is difficult to diagnose with imaging due to its absence of tears or anomalies. We aimed to clarify the accuracy of the preoperative diagnosis using magnetic resonance imaging (MRI). METHODS: The preoperative MRI status of the posterosuperior popliteomeniscal fascicle (sPMF), anteroinferior popliteomeniscal fascicle (iPMF), and popliteal hiatus were examined retrospectively on sagittal images in the hypermobile lateral meniscus group (n = 22) and an age- and gender-matched control group (n = 44). These statuses were evaluated by a logistic regression analysis to assess their degree of diagnostic accuracy. RESULTS: The area under the curve (AUC) of the sPMF, iPMF, popliteal hiatus, and all three criteria combined was 0.66, 0.74, 0.64, and 0.77, respectively (low, moderate, low, and moderate accuracy, respectively). The odds ratios of the most severe type 3 forms of the sPMF, iPMF, and popliteal hiatus for hypermobile lateral meniscus were significantly high (5.50, 12.20, and 5.00, respectively). Although the diagnostic accuracy was not high enough, the significantly higher odds ratio for type 3 may indicate a hypermobile lateral meniscus. CONCLUSION: a definitive diagnosis of hypermobile lateral meniscus is difficult with MRI findings alone; however, MRI evaluations of the iPMF, sPMF, and the widening of popliteal hiatus can be used as an adjunct to diagnosis.

CCL3-CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways.

Tumor-associated macrophages (TAMs) contribute to the progression and mortality of various malignancies. We reported that high numbers of infiltrating TAMs were significantly associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma (ESCC). In our previous investigation of TAMs' actions in ESCC, we compared gene expression profiles between peripheral blood monocyte (PBMo)-derived macrophages and TAM-like macrophages stimulated with conditioned media of ESCC cell lines. Among the upregulated genes in the TAM-like macrophages, we focused on CC chemokine ligand 3 (CCL3), which was reported to contribute to tumor progression in several malignancies. Herein, we observed that not only TAMs but also ESCC cell lines expressed CCL3. A CCL3 receptor, CC chemokine receptor 5 (CCR5) was expressed in the ESCC cell lines. Treating the ESCC cell lines with recombinant human (rh)CCL3 induced the phosphorylations of Akt and ERK, which were suppressed by CCR5 knockdown. Migration and invasion of ESCC cells were promoted by treatment with rhCCL3 and co-culture with TAMs. TAMs/rhCCL3-promoted cell migration and invasion were suppressed by inhibition of the CCL3-CCR5 axis, PI3K/Akt, and MEK/ERK pathways. Treatment with rhCCL3 upregulated MMP2 and VEGFA expressions in ESCC cell lines. Our immunohistochemical analysis of 68 resected ESCC cases showed that high expression of CCL3 and/or CCR5 in ESCC tissues was associated with poor prognosis. High CCR5 expression was associated with deeper invasion, presence of vascular invasion, higher pathological stage, higher numbers of infiltrating CD204+ TAMs, and higher microvascular density. High expression of both CCL3 and CCR5 was an independent prognostic factor for disease-free survival. These results suggest that CCL3 derived from both TAMs and cancer cells contributes to the progression and poor prognosis of ESCC by promoting cell migration and invasion via the binding of CCR5 and the phosphorylations of Akt and ERK. The CCL3-CCR5 axis could become the target of new therapies against ESCC.

NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells.

Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs.

Software-assisted morphometric and phenotype analyses of human peripheral blood monocyte-derived macrophages induced by a microenvironment model of human esophageal squamous cell carcinoma.

Human macrophages play important roles in tumor promotion and are called tumor-associated macrophages (TAMs). We previously demonstrated that human esophageal squamous cell carcinomas (ESCCs) contain TAMs and that these TAMs tend to have tumor-supporting features. Here we exposed human macrophages to conditioned media of TE-series human ESCC cell lines (TECMs) to generate an ESCC extracellular stimuli-influenced TAM model. CD14(+) peripheral blood monocytes (PBMos) from healthy donors were treated with M-CSF and with additional IL-4 or TECM exposure. Morphological changes of the cells and the induction of CD163/CD204 proteins were detected in the TECM-exposed model TAMs by immunofluorescence. A software-assisted immunofluorescent cell image analysis showed increased CD163/CD204 positivity in the model TAMs and a weak to moderate positive correlation between the cytoplasmic area and the sum fluorescent intensity of CD204. Morphological changes of the cells were significantly reflected by several cytomorphometric parameters. PBMos were elongated with M-CSF treatment, then enlarged with TECM exposure. The cytoplasmic aspect ratio was decreased by M-CSF treatment and slightly increased by TECM exposure. The nuclear-cytoplasmic ratio decreased during the whole process of cell differentiation. This system is useful for quantitative assessments of TAM-like morphological changes of macrophages and the induction of CD163/CD204 in a model ESCC microenvironment.

GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways.

Tumor-associated macrophages (TAMs) are known to be involved in the progression, angiogenesis, and motility of various cancers. We previously reported the association between an increased number of infiltrating TAMs with tumor progression and poor prognosis in esophageal squamous cell carcinomas (ESCCs). To study the roles of TAMs in ESCC, we first exposed peripheral blood monocyte (PBMo)-derived macrophages from healthy volunteers to conditioned media of TE series human ESCC cell line (TECM) and confirmed the induction of the expression of the M2 macrophage marker CD204 and the protumorigenic factors interleukin (IL)-10, VEGFA, and MMPs. Next, we compared gene expression profiles between PBMo-derived macrophages stimulated with or without TECM by cDNA microarray and focused on growth differentiation factor 15 (GDF15) among the highly expressed genes including IL-6, IL-8, and CXCL1. Our immunohistochemical study of 70 surgically resected ESCCs revealed that GDF15 was present not only in cancer cells but also in macrophages. The high expression of GDF15 in the ESCCs was significantly correlated with several more malignant phenotypes including vessel invasion, lymph node metastasis, and clinical stages. Patients with high GDF15 expression showed significantly poorer disease-free survival (P=0.011) and overall survival (P=0.041). We also found that recombinant human GDF15 promotes cell proliferation and the phosphorylation of both Akt and Erk1/2 in ESCC cell lines in vitro. These results indicate that GDF15 is secreted by both TAMs and cancer cells in the tumor microenvironment and is associated with aberrant growth and a poor prognosis in human ESCC.

Application of gel permeation HPLC for lipoprotein profiling in dogs.

A high performance liquid chromatography system with a gel permeation column (GP-HPLC) and an on-line dual enzymatic system was applied to lipoprotein analysis in dogs. A high density lipoprotein (HDL) fraction obtained by conventional ultracentrifugation gave a single peak at around 28-29 min. Similarly, a low density lipoprotein (LDL) fraction gave single peak at around 24-25 min. The lipoprotein profiles of healthy dogs were contained large HDL peaks and small LDL peaks, and VLDL and CM were only marginally detected. In diabetic dogs, concentrations of VLDL-triglyceride and VLDL-total-cholesterol were elevated significantly. The lipoprotein profile analysis by GP-HPLC method would be useful in explication of abnormality of lipid metabolism in dogs.