The role of thromboxane prostanoid receptor signaling in gastric ulcer healing.

The process of gastric ulcer healing includes cell migration, proliferation, angiogenesis and re-epithelialization. Platelets contain angiogenesis stimulating factors that induce angiogenesis. Thromboxane A2 (TXA2 ) not only induces platelet activity but also angiogenesis. This study investigated the role of TXA2 in gastric ulcer healing using TXA2 receptor knockout (TPKO) mice. Gastric ulcer healing was suppressed by treatment with the TXA2 synthase inhibitor OKY-046 and the TXA2 receptor antagonist S-1452 compared with vehicle-treated mice. TPKO showed delayed gastric ulcer healing compared with wild-type mice (WT). The number of microvessels and CD31 expression were lower in TPKO than in WT mice, and TPKO suppressed the expression of transforming growth factor beta (TGF-ß) and vascular endothelial growth factor A (VEGF-A) in areas around gastric ulcers. Immunofluorescence assays showed that TGF-ß and VEGF-A co-localized with platelets. Gastric ulcer healing was significantly reduced in WT mice transplanted with TPKO compared with WT bone marrow. These results suggested that TP signalling on platelets facilitates gastric ulcer healing through TGF-ß and VEGF-A.

The knee position at tourniquet inflation does not affect the gap balancing during total knee arthroplasty.

INTRODUCTION: The relationship between gap balancing and clinical outcome of total knee arthroplasty (TKA) has been researched. Tourniquet is widely used by most surgeons; however, there are little quantitative data about the gap depending on the tourniquet usage. We aimed to investigate whether the knee position at tourniquet inflation affected the gap measurement intra-operatively. METHODS: TKA was performed for 104 knees and the tourniquet was inflated with the knee at full flexion and extension. The gap was measured in each static knee flexion status (0°, 30°, 45°, 60°, 90°, 120°, and in full flexion) using a tensor. We measured the gap twice; under the tourniquet inflation and release. The gap difference at each static knee flexion status was calculated by subtracting the gap under release from that under inflation. RESULTS: When the tourniquet was inflated with the knee at full flexion, the mean gap differences were < 1 mm and < 1° in each static knee flexion status. When the tourniquet was inflated with the knee at full extension, the mean gap differences were < 1 mm and < 1°, respectively. All values of the gap difference were minimum, and were not affected by the tourniquet, whether the knee position at the tourniquet inflation was flexed or extended. CONCLUSIONS: We postulated that the knee position at tourniquet inflation would affect the gap, which was refuted by our results. This shows that we can measure the gap without considering the knee position at tourniquet inflation.

Accuracy of tibial component placement in unicompartmental knee arthroplasty performed using an accelerometer-based portable navigation system.

PURPOSE: There is a need for new devices to improve the accuracy of implantation in unicompartmental knee arthroplasties (UKAs). The accelerometer-based portable navigation system is expected to improve this accuracy. This study aimed to compare the accuracy of UKAs performed by the portable navigation system with that of the conventional method, and to investigate whether the portable navigation system can complement the surgeon's experience. METHODS: The study comprised of 80 Oxford UKAs. Knees were divided into two groups based on the method of tibial osteotomy: the conventional group (37 UKAs performed by an experienced surgeon using the extra-medullary guide) and the portable navigation group (43 UKAs performed by 2 unaccustomed surgeons using the navigation system). The absolute error from the target angle on the coronal and sagittal plane was measured on whole lower leg X-ray. The incidence of outliers (> 3°) was compared between the groups using Fisher's exact probability test. RESULTS: The incidences of outliers on the coronal plane were 41.0% (15 of 37 knees) in the conventional group and 9.3% (4 of 43 knees) in the portable navigation group (p < 0.0001). The incidences of outliers on the sagittal plane were 13.5% (5 of 37 knees) in the conventional group and 14.0% (6 of 43 knees) in the portable navigation group (p = 0.3772). CONCLUSION: This is the first report on the usefulness of an accelerometer-based portable navigation system in UKA. The use of this system improves the accuracy of implantation of the tibial component beyond the experience of the surgeon. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

[Introduction of Minimally Invasive Thoracoscopic Surgery for the Anterior Mediastinum;Subxiphoid Video-assisted Thoracoscopic Thymectomy and Robot-assisted Thymectomy].

In Japan, robot-assisted surgery for malignant lung tumors, benign mediastinal tumors, and malignant mediastinal tumors has been covered by the national health insurance since 2018. Hence, the number of domestic robotic surgical procedures is increasing. Recently, we introduced endoscopic surgery such as video-assisted thoracoscopic surgery (VATS) via a subxiphoidal approach for thymectomy. Here, we compared VATS and robotic surgery via a subxiphoidal approach in terms of clinical factors. During the study period, 5 consecutive patients who underwent robotic thymectomy and 24 patients who underwent VATS were analyzed. Although the operative time was longer in the robotic group, the intraoperative blood loss, postoperative length of stay, and postoperative complications were favorable in the robotic group. The disadvantage of robotic surgery is the necessity for a reduction in operative time including console duration time. However, future developments in the field of robotic engineering will lead to the creation of systems that allow for more advanced surgical techniques. We must chose procedures in consideration of the best method for each patient, and it is necessary to perform robotic surgery based on the expense and therapeutic effect, social environment, and way of life of each patient.

Changes in postoperative extension angle after total knee arthroplasty: Effect of polyethylene insert thickness.

BACKGROUND: Flexion contracture is a serious complication after total knee arthroplasty (TKA). Polyethylene insert (PE) thicker than the extension gap during surgery causes flexion contracture. The purpose of this study was to identify the changes over time in postoperative extension angle and the correlation between extension gap and PE thickness. METHODS: Overall, 127 knees were analyzed to evaluate the changes in extension angle over time. "Gap difference" was defined as the distance obtained by subtracting the extension gap from the PE thickness. Patients were divided into four groups according to gap difference (0-3 or greater mm). We evaluated the correlation of gap difference and changes in postoperative extension angle over time. RESULTS: The extension angles of all knees were -4.2 ± 3.9 (deg. mean ± s.d.) at surgery, -5.9 ± 5.7 at 3 months, -3.4 ± 5.4 at 6 months, and -1.3 ± 5.4 at 2 years. Gap difference was negatively correlated with the extension angle at surgery and at 2 years (r = 0.40, r = 0.36). The extension angles at 2 years in each group (groups 0, 1, 2, 3 or greater) were 2.0°±4.7°, -0.8°±5.3°, -3.4°±5.3°, -4.0°±4.1° (p < 0.05), respectively. CONCLUSIONS: The extension angle became worse at 3 months compared to that at surgery (p = 0.01) and then improved until 2 years. The correlation between gap difference and extension angle was maintained at 2 years, and thicker PE caused flexion contracture even after 2 years. Hence, PE selection considering the extension gap is important.

Angiotensin II subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation.

Liver metastases from colorectal cancer (CRC) are a clinically significant problem. The renin-angiotensin system is involved in tumor growth and metastases. This study was designed to evaluate the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in CRC. A model of liver metastasis was developed by intrasplenic injection of mouse colon cancer (CMT-93) into AT1a knockout mice (AT1aKO) and wild-type (C57BL/6) mice (WT). Compared with WT mice, the liver weight and liver metastatic rate were significantly lower in AT1aKO. The mRNA levels of CD31, transforming growth factor- ß1 (TGF-ß1), and F4/80 were suppressed in AT1aKO compared with WT. Double immunofluorescence analysis showed that the number of accumulated F4/80+ cells expressing TGF-ß1 in metastatic areas was higher in WT than in AT1aKO. The AT1aKO bone marrow (BM) (AT1aKO-BM)→WT showed suppressed formation of liver metastasis compared with WT-BM→WT. However, the formation of metastasis was further suppressed in WT-BM→AT1aKO compared with AT1aKO-BM→WT. In addition, accumulated F4/80+ cells in the liver metastasis were not BM-derived F4/80+ cells, but mainly resident hepatic F4/80+ cells, and these resident hepatic F4/80+ cells were positive for TGF-ß1. Angiotensin II enhanced TGF-ß1 expression in Kupffer cells. Treatment of WT with clodronate liposomes suppressed liver metastasis by diminishing TGF-ß1+ F4/80+ cells accumulation. The formation of liver metastasis correlated with collagen deposition in the metastatic area, which was dependent on AT1a signaling. These results suggested that resident hepatic macrophages induced liver metastasis formation by induction of TGF-ß1 through AT1a signaling.

Decreased extension gap and valgus alignment after implantation of total knee prosthesis in primary varus knees.

PURPOSE: It was hypothesised that implantation of a total knee prosthesis may change the size and shape of the joint gap. To test this hypothesis, a tensor device was used which was specifically designed to reproduce the conditions before and after implantation, including attachment of the polyethylene insert trial. This study aimed to compare the joint gaps before and after implantation of a total knee prosthesis using this new tensor device. METHODS: A total of 259 primary varus knees were included in this study. Knees were exposed using a medial parapatellar approach, and the anterior and posterior cruciate ligaments were resected. After the trial reduction, the intraoperative joint gap kinematics was measured using the tensor device. RESULTS: Implantation of a total knee prosthesis decreased the size of the extension joint gap and made it valgus, but did not influence the size or shape of the flexion joint gap. CONCLUSIONS: The present findings suggest that the classical gap technique, which creates equal and rectangular extension and flexion joint gaps in the bone cutting surface, results in an imbalance between the extension and flexion joint gaps after implantation. To achieve equal and rectangular extension and flexion joint gaps after implantation, the prepared extension joint gap should be about 2 mm larger than the flexion joint gap and slightly varus before implantation in primary varus knees. LEVEL OF EVIDENCE: Therapeutic study, Level II.

The effect of tourniquets on patellofemoral joint congruity during total knee arthroplasty.

BACKGROUND: Incongruity of the patellofemoral joint after total knee arthroplasty (TKA) causes anterior knee pain. Intraoperative congruity tests are necessary to avoid unnecessary lateral retinacular release, and the usage of tourniquets may influence these results. The purpose of this study was to examine the effect of tourniquets on patellofemoral joint congruity during TKA. MATERIALS AND METHODS: Two hundreds and seventeen knees were examined after TKA. Skyline radiographs at 60° and 90° flexion were taken immediately after wound closure before and after tourniquet deflation to compare changes in patellar tilt angle. RESULTS: In the patellar tilt angle at 60° flexion, lateral tilt was observed in 18 knees. Tourniquet deflation changed the patellar tilt angle by a mean -0.7° ± 1.2° (p = 0.030). Medial tilt was observed in 10 knees. Tourniquet deflation changed the patellar tilt angle by 0.9° ± 0.7° (p = 0.004). Tourniquet deflation improved the degree of lateral and medial patellar tilt. In the patellar tilt angle at 90° flexion, lateral tilt was observed in 118 knees. Tourniquet deflation changed the patellar tilt angle by a mean -1.1° ± 1.2° (p < 0.001). Medial tilt was observed in 71 knees. Tourniquet deflation changed the patellar tilt angle by 0.5° ± 1.0° (p < 0.001). Tourniquet deflation improved the degree of lateral and medial patellar tilt. CONCLUSIONS: Tourniquet deflation improved patellofemoral congruity in a statistically significant way, but only to a small extent, indicating low clinical significance. Therefore, intraoperative congruity tests performed with tourniquets in place are reliable.

The role of vascular endothelial growth factor receptor-1 signaling in compensatory contralateral lung growth following unilateral pneumonectomy.

Compensatory lung growth models have been widely used to investigate alveolization because the remaining lung can be kept intact and volume loss can be controlled. Vascular endothelial growth factor (VEGF) plays an important role in blood formation during lung growth and repair, but the precise mechanisms involved are poorly understood; therefore, the aim of this study was to investigate the role of VEGF signaling in compensatory lung growth. After left pneumonectomy, the right lung weight was higher in VEGF transgenic mice than wild-type (WT) mice. Compensatory lung growth was suppressed significantly in mice injected with a VEGF neutralizing antibody and in VEGF receptor-1 tyrosine kinase-deficient mice (TK(-/-) mice). The mobilization of progenitor cells expressing VEGFR1(+) cells from bone marrow and the recruitment of these cells to lung tissue were also suppressed in the TK(-/-) mice. WT mice transplanted with bone marrow from TK(-/-)transgenic GFP(+) mice had significantly lower numbers of GFP(+)/aquaporin 5(+), GFP(+)/surfactant protein A(+), and GFP(+)/VEGFR1(+) cells than WT mice transplanted with bone marrow from WTGFP(+) mice. The GFP(+)/VEGFR1(+) cells also co-stained for aquaporin 5 and surfactant protein A. Overall, these results suggest that VEGF signaling contributes to compensatory lung growth by mobilizing VEGFR1(+) cells.

Magnetic stripes and skyrmions with helicity reversals.

It was recently realized that topological spin textures do not merely have mathematical beauty but can also give rise to unique functionalities of magnetic materials. An example is the skyrmion--a nano-sized bundle of noncoplanar spins--that by virtue of its nontrivial topology acts as a flux of magnetic field on spin-polarized electrons. Lorentz transmission electron microscopy recently emerged as a powerful tool for direct visualization of skyrmions in noncentrosymmetric helimagnets. Topologically, skyrmions are equivalent to magnetic bubbles (cylindrical domains) in ferromagnetic thin films, which were extensively explored in the 1970s for data storage applications. In this study we use Lorentz microscopy to image magnetic domain patterns in the prototypical magnetic oxide-M-type hexaferrite with a hint of scandium. Surprisingly, we find that the magnetic bubbles and stripes in the hexaferrite have a much more complex structure than the skyrmions and spirals in helimagnets, which we associate with the new degree of freedom--helicity (or vector spin chirality) describing the direction of spin rotation across the domain walls. We observe numerous random reversals of helicity in the stripe domain state. Random helicity of cylindrical domain walls coexists with the positional order of magnetic bubbles in a triangular lattice. Most unexpectedly, we observe regular helicity reversals inside skyrmions with an unusual multiple-ring structure.

Angiotensin II type 1A receptor signaling facilitates tumor metastasis formation through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells.

Angiotensin II is involved in tumor growth; however, the precise mechanism is not known. Platelets also contribute to tumor growth, and angiotensin II type 1 receptor (AT1) is expressed on the platelet surface. We hypothesized that interaction of platelets with tumor cells through AT1 receptor signaling promotes tumor metastasis. B16F1 melanoma cells were intravenously injected into Agtr1a knockout mice (AT1a(-/-)) and wild-type littermates (WT); the AT1a(-/-) mice exhibited a reduction in lung colonies. Angiotensin II induced expression of P-selectin on platelets in WT but not in AT1a(-/-) mice. A selective P-selectin neutralizing antibody decreased lung colony numbers in WT but not in AT1a(-/-) mice. Levels of vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1) receptor in platelets at metastatic locus were lower in AT1a(-/-) mice. Treatment of neutralizing antibodies against VEGF and CXCR4 decreased lung colony numbers in WT but not in AT1a(-/-) mice. In AT1a(-/-) mice, and both mobilization of progenitor cells expressing CXCR4(+)VEGFR1(+) cells from bone marrow and their recruitment to lung tissues were suppressed. These results suggest that AT1A signaling plays a critical role in tumor metastasis through P-selectin-mediated interactions of platelets with tumor and endothelial cells and through the AT1A signaling-dependent production of VEGF and SDF-1, which may be involved in mobilization of CXCR4(+)VEGFR1(+) cells.

Clinical impact of lung age on postoperative complications in non-small cell lung cancer patients aged >70 y.

BACKGROUND: Surgery for elderly patients with primary lung neoplasms has become relatively common as populations age; however, the high frequency of postoperative complications has prevented its broad application. Recently, the Japanese Respiratory Society proposed lung age (LA) as an index of lung function, but reports on the association between LA and the risk factors for postoperative complications with non-small cell lung cancer (NSCLC) surgery have been limited. In this study, we analyzed the clinical applicability of LA for elderly patients with NSCLC. MATERIALS AND METHODS: We studied 320 patients aged >70 y underwent curative resections for NSCLC. LA was calculated based on the formula provided by the Japanese Respiratory Society, which depended on the patient's preoperative respiratory function and was divided into four age gap (AG) groups between the LA and the true age (TA). The categorical data were compared among the four groups. RESULTS: The numbers of patients in groups A, B, C, and D were 80, 77, 79, and 84, respectively. For the univariate analysis, the preoperative factors for postoperative complications were gender, AG, and smoking (P < 0.05). In a multivariate analysis, AG proved to be an independent factor. Although we found no significant differences, there was a tendency for the prognosis to worsen with an increase in the AG (P = 0.06). CONCLUSIONS: The AG was significantly associated with and an independent predictive factor for postoperative complications. We conclude that LA and AG are useful factors for predicting the risk of postoperative complications.

Joint gap measurement in total knee arthroplasty using a tensor device with the same articulating surface as the prosthesis.

BACKGROUND: We developed a new tensor to measure the joint gap throughout knee flexion during total knee arthroplasty (TKA). This tensor has the same articular shape as that of the tibial liner, including the post structure and the curvature of femorotibial articular surface, to measure the gap intraoperatively under the same conditions as after TKA. The present study aimed to examine the precision of the new tensor for gap measurement after implantation. METHODS: We performed TKA using the modified gap technique in four cadaveric knees and measured the gaps using the new tensor. The intra-observer and inter-observer error of the tensor was analyzed using 168 measurements of the gaps as determined at least twice by two surgeons. In addition, the gaps in rotating-platform posterior-stabilized TKA were measured at seven positions with the knee bending from extension to full flexion. RESULTS: The inter-observer and intra-observer errors were 0.8 and 0.3 mm, respectively, indicating precise and reproducible gap measurement. The gaps before implantation in reduced patellar position were 12.1 mm at extension and 12.5 mm at 90° flexion. The gaps after implantation were 9.1, 12.9, 13.1, 13.5, 13.8, 13.3, and 10.1 mm at 0°, 30°, 45°, 60°, 90°, 120°, and full flexion, respectively. CONCLUSIONS: The new tensor provides precise and reproducible measurements. Although the joint gap before implantation was parallel and equal at extension and 90° flexion, the joint gap after implantation was variable throughout knee flexion. This feature of the gap should be considered during the operation.

Element-selective imaging of atomic columns in a crystal using STEM and EELS.

Microstructure characterization has become indispensable to the study of complex materials, such as strongly correlated oxides, and can obtain useful information about the origin of their physical properties. Although atomically resolved measurements have long been possible, an important goal in microstructure characterization is to achieve element-selective imaging at atomic resolution. A combination of scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS) is a promising technique for atomic-column analysis. However, two-dimensional analysis has not yet been performed owing to several difficulties, such as delocalization in inelastic scattering or instrumentation instabilities. Here we demonstrate atomic-column imaging of a crystal specimen using localized inelastic scattering and a stabilized scanning transmission electron microscope. The atomic columns of La, Mn and O in the layered manganite La1.2Sr1.8Mn2O7 are visualized as two-dimensional images.

The intact posterior cruciate ligament not only controls posterior displacement but also maintains the flexion gap.

BACKGROUND: The PCL is a strong stabilizer of the knee and provides posterior stability to the tibia. However, sagittal alignment of the PCL with the knee at 90° flexion suggests the PCL might play a role not only in posterior stabilization but also in maintaining the flexion gap. QUESTIONS/PURPOSES: We determined whether the intact PCL helps maintain the flexion gap. METHODS: We examined axial radiographs and gravity sag views of 17 patients with chronic isolated unilateral PCL injury. The flexion gap was defined as the mean value of the medial and lateral distances between the femoral and tibial bones on the axial radiograph. Increase in the flexion gap and posterior laxity were determined by comparing the patients' injured and contralateral uninjured knees. RESULTS: The flexion gap of PCL injured knees (median, 7.5 mm; range, 5.3-11.5 mm; medial median, 6.2 mm; medial range, 3.7-8.3 mm; lateral median, 7.9 mm; lateral range, 5.3-11.5 mm) was larger than that seen in uninjured knees (median, 5.0 mm; range, 4.0-7.6 mm; medial median, 4.6 mm; medial range 3.4-7.1 mm; lateral median, 5.6; lateral range, 4.5-11.2 mm). The increment in the medial distance was similar to that in the lateral distance. Posterior laxity of injured knees was 9.1 (median); 5.4 to 15.2 (range) mm greater than that of uninjured knees. We found no correlation between posterior laxity and the flexion gap increment. CONCLUSIONS: Our data suggest the intact PCL controls posterior displacement and maintains the flexion gap.

Prognostic implications of prostaglandin E-major urinary metabolite in resected non-small-cell lung cancer.

OBJECTIVES: Cyclooxygenase-2-derived prostaglandin E2 (PGE2) is highly involved in the promotion of cancer progression. The end product of this pathway, PGE-major urinary metabolite (PGE-MUM), is a stable metabolite of PGE2 that can be assessed non-invasively and repeatedly in urine samples. The aim of this study was to assess the dynamic changes in perioperative PGE-MUM levels and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS: Between December 2012 and March 2017, 211 patients who underwent complete resection for NSCLC were analysed prospectively. PGE-MUM levels in 2 spot urine samples taken 1 or 2 days preoperatively and 3-6 weeks postoperatively were measured using a radioimmunoassay kit. RESULTS: Elevated preoperative PGE-MUM levels were associated with tumour size, pleural invasion and advanced stage. Multivariable analysis revealed that age, pleural invasion, lymph node metastasis and postoperative PGE-MUM levels were independent prognostic factors. In matched pre- and postoperative urine samples obtained from patients who are eligible for adjuvant chemotherapy, an increase in PGE-MUM levels following resection was an independent prognostic factor (hazard ratio 3.017, P = 0.005). Adjuvant chemotherapy improved survival in patients with increased PGE-MUM levels after resection (5-year overall survival, 79.0 vs 50.4%, P = 0.027), whereas survival benefit was not observed in those with decreased PGE-MUM levels (5-year overall survival, 82.1 vs 82.3%, P = 0.442). CONCLUSIONS: Increased preoperative PGE-MUM levels can reflect tumour progression and postoperative PGE-MUM levels are a promising biomarker for survival after complete resection in patients with NSCLC. Perioperative changes in PGE-MUM levels may aid in determining the optimal eligibility for adjuvant chemotherapy.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

BACKGROUND: The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. METHODS: From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. RESULTS: We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p = 0.551). CONCLUSION: Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Thromboxane A2 receptor signaling facilitates tumor colonization through P-selectin-mediated interaction of tumor cells with platelets and endothelial cells.

Thromboxane A(2) (TXA(2) ) is a prostanoid formed by thromboxane synthase using the cyclooxygenase product, prostaglandin H(2), as the substrate. TXA(2) was shown to enhance tumor metastasis, but the underlying mechanism remains unclear. B16F1 melanoma cells were intravenously injected into TXA(2) receptor (TP) knockout mice (TP(-/-) ) and wild-type littermates (WT). TP(-/-) showed a reduction in B16F1 lung colonization and mortality rate, which were associated with a decreased number of platelets. Platelet activation as assessed by P-selectin expression was suppressed in TP(-/-) . A selective P-selectin neutralizing antibody decreased the lung colonization in WT mice, but not in TP(-/-) . The expression of P-selectin glycoprotein ligand-1 in B16F1 and HUVEC were enhanced by treatment with U46619, a thromboxane analog. The plasma levels of vascular endothelial growth factor (VEGF) and stromal-derived factor (SDF)-1 were lower in TP(-/-) . In TP(-/-) , the mobilization of progenitor cells expressing CXCR4(+) VEGFR1(+) from bone marrow and the recruitment of those cells to lung tissues were suppressed. These results suggest that TP signaling plays a critical role in tumor colonization through P-selectin-mediated interactions between platelets-tumor cells and tumor cells-endothelial cells through the TP signaling-dependent production of VEGF and SDF-1, which might be involved in the mobilization of VEGFR1(+) CXCR4(+) cells. Blockade of TP signaling might be useful in the treatment of tumor metastasis.

Mid-term clinical results of alumina medial pivot total knee arthroplasty.

PURPOSE: The medial pivot total knee prosthesis has been designed to reproduce physiological knee kinematics. It has been reported that alumina ceramic femoral components reduce polyethylene wear. Thus, medial pivot total knee prostheses with alumina ceramic femoral components were introduced. The purpose of this study was to evaluate the clinical results of patients who underwent newly introduced alumina medial pivot total knee arthroplasties (TKA). METHODS: We evaluated the clinical results of 107 alumina medial pivot TKAs in 80 consecutive patients with a mean follow-up period of 5 years. RESULTS: Alumina medial pivot TKAs provided significant improvements in the patients' Knee Society knee scores, function scores and post-operative ranges of motion compared with their pre-operative statuses (each, P < 0.05). There was no statistical correlation between the change in maximum knee flexion and the increase in posterior condylar offset. Revision surgery was required in one knee due to a post-operative fracture of the tibial plateau after a fall that occurred 2 years postoperatively. No knees had aseptic loosening, osteolysis, or ceramic fractures. The survival rate was 98.6% at 5 years. CONCLUSIONS: This study demonstrates satisfactory mid-term clinical results for patients receiving the alumina medial pivot prosthesis. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

Selection of preoperative stress electrocardiography test for appropriate patients with non-small cell lung cancer.

OBJECTIVE: Lobectomy is an established surgical procedure for treating non-small cell lung cancer; however, it significantly impacts postoperative cardiac function. The stress electrocardiography test is relatively easy to perform and is used to confirm the presence of coronary artery stenotic lesions. However, it has a low pre-test probability and may yield many false positives. We examined the factors that would enable the appropriate selection of patients for stress electrocardiography as a preoperative cardiovascular examination preceding lobectomy for non-small cell lung cancer. METHODS: From June 2016 to July 2018, 240 patients at our institution who underwent stress electrocardiography before lobectomy for primary lung cancer were included in this study. Clinical information was extracted from electronic medical records and evaluated retrospectively. Smoking history, diabetes, hypertension, dyslipidemia, and ischemic heart disease were considered risk factors for coronary artery stenosis. We determined the coronary risk factors that were applicable to each participant and calculated the total number of coronary risk factors as a risk score. RESULTS: Patients with coronary risk factor scores of ≥ 3 were significantly more likely to have abnormal stress electrocardiography results. In addition, these patients also underwent more comprehensive examinations to identify coronary diseases. There were no patients with complications that could be attributed to ischemic heart disease. CONCLUSION: Stress electrocardiography may be more useful before lobectomy in non-small cell lung cancer patients if the patients are appropriately selected, with the test utilized mainly in patients with coronary risk factor scores of ≥ 3.