Progressive Bone Destruction in Rapidly Destructive Coxopathy Is Characterized by Elevated Serum Levels of Matrix Metalloprotease-3 and C-Reactive Protein.

OBJECTIVE: Rapidly destructive coxopathy (RDC) is a rare condition characterized by rapid joint space narrowing; however, its pathology remains unclear. This study aimed to clarify the association of laboratory biomarkers with the radiological progression of RDC. METHODS: We examined 34 female and 4 male patients with RDC between October 2010 and April 2018. Patients were divided into 3 groups according to the progressive radiographic staging of RDC. Group 1 patients had progressive obliteration of the joint space without subchondral destruction (n = 11), group 2 had progressed subchondral destruction (n = 18), and group 3 had cessation of bone destruction observed for more than 6 months (n = 9). Clinical evaluation results were assessed using the Japanese Orthopedic Association hip score. Blood test results, including serum matrix metalloproteinase-3 (MMP-3), and C-reactive protein (CRP), were also evaluated. RESULTS: There were no significant differences in patient background or Japanese Orthopedic Association hip scores among the groups. However, there were significant differences in MMP-3 levels among groups, with MMP-3 levels in group 2 being significantly higher than those in group 3 (group 2, 118.4 ± 81.2 ng/mL; group 3, 42.5 ± 15.1 ng/mL, p < 0.001). The CRP levels in group 2 were also significantly higher than those in group 3 (group 2, 0.77 ± 0.92 mg/dL; group 3, 0.13 ± 0.07 mg/dL, p = 0.019), but elevated CRP levels in group 2 decreased back to the reference range. CONCLUSIONS: Matrix metalloproteinase-3 and CRP are the biomarkers of RDC progression but not of its occurrence. Severe inflammatory response may be associated with bone destruction in RDC.

Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats.

The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6 h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.

Causes of peritoneal injury during laparoscopic totally extraperitoneal inguinal hernia repair and methods of repair.

INTRODUCTION: Peritoneal injury during laparoscopic totally extraperitoneal (TEP) inguinal hernia repair is an intraoperative complication that affects accomplishment. We retrospectively examined the causes of peritoneal injury and methods of TEP repair. METHODS: This study examined 58 patients with inguinal hernia (43 unilateral, 15 bilateral) who had undergone TEP repair; all procedures were performed by the same surgeon. The incidence of peritoneal injury, clinical characteristics that could have influenced peritoneal injury, and management of the injury were analyzed. RESULTS: Peritoneal injury was noted in 16 inguinal hernias (21.9%, 16 /73). Injury occurred more frequently in right-sided hernias than in left-sided hernias (31.6% vs 11.4%, P = .049). No other factors were related to injury. Peritoneal injury occurred due to anatomical misrecognition in five hernias (31.3%, 5/16) and unintentional dissection in six hernias (37.5%, 6/16). All injuries due to unintentional dissection occurred in right-sided hernias. The procedures used for peritoneal injury repair were endoscopic suturing for 4 hernias, pre-tied loop ligation for 1 hernia, and ligation clips in 11 hernias. Additional techniques were required in three hernias repaired by endoscopic suturing (75% 3/4). After introduction of the ligation clips, endoscopic suturing was discontinued, and no additional techniques were needed. CONCLUSION: Peritoneal injury more frequently occurred in right-sided inguinal hernia than in left-sided inguinal hernia during TEP repair. The common reasons for peritoneal injury were anatomical misrecognition and unintentional dissection. Repair using ligation clips is the best option for peritoneal injuries that occur during TEP repair.

Tailor-made Surgical Guide Reduces Incidence of Outliers of Cup Placement.

UNLABELLED: Malalignment of the cup in total hip arthroplasty (THA) increases the risks of postoperative complications such as neck cup impingement, dislocation, and wear. We asked whether a tailor-made surgical guide based on CT images would reduce the incidence of outliers beyond 10 degrees from preoperatively planned alignment of the cup compared with those without the surgical guide. We prospectively followed 38 patients (38 hips, Group 1) having primary THA with the conventional technique and 31 patients (31 hips, Group 2) using the surgical guide. We designed the guide for Group 2 based on CT images and fixed it to the acetabular edge with a Kirschner wire to indicate the planned cup direction. Postoperative CT images showed the guide reduced the number of outliers compared with the conventional method (Group 1, 23.7%; Group 2, 0%). The surgical guide provided more reliable cup insertion compared with conventional techniques. LEVEL OF EVIDENCE: Level II, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Therapeutic experience with tramadol for opioid dependence in a patient with chronic low back pain: a case report.

BACKGROUND: Long-term opioid treatment for chronic non-cancer pain has become controversial, given the increasing prevalence of opioid dependence. However, there is little information on therapeutic strategies for this condition in Japanese patients. Here, we present a case of successful management of iatrogenic opioid dependence with tramadol in a patient with chronic low back pain. CASE PRESENTATION: A 68-year-old male suffering from intractable low back pain was referred to our pain clinic. He was previously treated in another hospital with transdermal fentanyl patches 6 mg/day and fentanyl sublingual tablets (100 µg as required) for this condition. On the basis of medical examination, including a review of the patient's medical history, physical examination, X-ray, and his family statement, we diagnosed him with iatrogenic opioid dependence due to inadequate fentanyl use. Then, we developed a treatment plan consisting in fentanyl detoxification with a weak opioid, tramadol. At first, the use of fentanyl sublingual tablets was interrupted after obtaining informed consent. Then, we reduced the dose of transdermal fentanyl 1 mg per 4-5 days replacing with oral sustained-release tramadol. The patient developed mild to moderate withdrawal symptoms during this period, which could be effectively managed by supportive treatments. The hospital psychiatry liaison team continuously provided the patient and his wife with information, counseling, and education regarding the treatment of opioid dependence. Throughout the detoxification process, his reported pain did not exacerbate, even slightly improved over time. The final prescription was sustained-release tramadol 300 mg/day without fentanyl, and his activities of daily living drastically improved. However, unfortunately, he died due to an aortic dissection of stent-graft edge 65 days after surgery. CONCLUSIONS: Our case highlighted that sustained-release tramadol could be effectively applied as a detoxification agent for iatrogenic opioid dependence in patients with chronic non-cancer pain.

Immunoglobulin G4-Related Disease of the Hip.

The authors report a case of immunoglobulin G4-related disease (IgG4-RD) of the hip. A 60-year-old man diagnosed with osteoarthritis of the right hip was referred to the authors' outpatient clinic for surgical intervention. Laboratory test results revealed elevated C-reactive protein and serum IgG levels. A subsequent laboratory test revealed an IgG4 level of 318 mg/dL. Magnetic resonance imaging revealed an abnormal mass in the right hip joint. The authors suspected IgG4-RD of the hip. The mass was resected during total hip arthroplasty. Immunohistochemical analysis for IgG revealed positive staining of many plasma cells. Most of the IgG-positive plasma cells were positive for IgG4, and the ratio of IgG4/IgG-positive cells was 51%. This case met all criteria for IgG4-RD; thus, the authors made a definitive diagnosis of IgG4-RD of the hip. The C-reactive protein level decreased to a negative value, and the IgG level decreased to a normal range at 3 weeks postoperatively. The IgG4 level gradually decreased to 152 mg/dL at 5 months postoperatively. This is the first reported case of IgG4-RD of the hip joint. [Orthopedics. 2018; 41(6):e876-e879.].

Fluoroscopic bone fragment tracking for surgical navigation in femur fracture reduction by incorporating optical tracking of hip joint rotation center.

A new method for fluoroscopic tracking of a proximal bone fragment in femoral fracture reduction is presented. The proposed method combines 2-D and 3-D image registration from single-view fluoroscopy with tracking of the head center position of the proximal femoral fragment to improve the accuracy of fluoroscopic registration without the need for repeated manual adjustment of the C-arm as required in stereo-view registrations. Kinematic knowledge of the hip joint, which has a positional correspondence with the femoral head center and the pelvis acetabular center, allows the position of the femoral fragment to be determined from pelvis tracking. The stability of the proposed method with respect to fluoroscopic image noise and the desired continuity of the fracture reduction operation is demonstrated, and the accuracy of tracking is shown to be superior to that achievable by single-view image registration, particularly in depth translation.

[MRI-based surgical simulation of transtrochanteric rotational osteotomy for osteonecrosis of the femoral head].

Transtrochanteric rotational osteotomy (TRO) is one of the joint-preserving surgical treatments for osteonecrosis of the femoral head (ONFH). It can prevent collapse of the femoral head as necrotic lesions in the weight-bearing portion can be moved sufficiently to less weight-bearing portion by anterior rotation, posterior rotation or varus angulation. Patient selection and preoperative planning are important to determine indications for TRO. It has been reported that successful TRO requires at least 34% of the weight-bearing area supported by the intact part of the femoral head. However, this ratio is difficult to preoperatively quantify according to the rotation angle using conventional two-dimensional MR images or X-rays. Therefore, we developed a method of simulating TRO using three-dimensional (3-D) models reconstructed from 3-D MR images and applied it to serial patients with types C1 and C2 osteonecrosis at stage 1 or 2. The simulation visualized positional changes of the necrotic lesion in the weight-bearing area and enabled quantitation of the postoperative intact ratio. Our surgical simulation is useful for evaluating the postoperative intact ratio and for determining indications for TRO as well as the optimal angle of femoral head rotation and varus angulation.

Radiologic and Clinical Features of Misdiagnosed Idiopathic Osteonecrosis of the Femoral Head.

Idiopathic osteonecrosis of the femoral head (ONFH) can be correctly diagnosed in accordance with the established criteria. However, some general orthopedic physicians have misdiagnosed patients as having ONFH. The goal of this study was to clarify the radiologic and clinical features of misdiagnosed patients. This study included 50 patients who were referred to the authors' hospital by general physicians with a diagnosis of ONFH. The correct diagnosis was made based on the Japanese Investigation Committee diagnostic criteria for ONFH. Demographic data were compared between patients with and without ONFH. Of the 50 patients, 24 were diagnosed with other diseases: 10 with osteoarthritis, 7 with transient osteoporosis of the femoral head, 4 with rapidly destructive coxopathy, and 3 with subchondral insufficiency fracture. Seventeen patients who did not have ONFH had magnetic resonance imaging findings that showed a bone marrow edema pattern at the femoral head. The mean age of 62.9 years among patients without ONFH was significantly higher than that of 45.2 years among patients with ONFH. There were 18 female patients in the non-ONFH group and 5 female patients in the ONFH group. Bilateral disease was found in 1 patient in the non-ONFH group and 17 patients in the ONFH group. No patients in the non-ONFH group had a history of systemic steroid administration compared with 11 patients in the ONFH group. Clinical features associated with the non-ONFH group were female sex, older age, unilateral disease, and no history of systemic steroid administration. For patients with these features, the diagnosis of ONFH should be made carefully. [Orthopedics. 2017; 40(1):e117-e123.].

Chronic Expanding Hematoma After Metal-on-Metal Total Hip Arthroplasty.

A 76-year-old woman who underwent bilateral metal-on-metal total hip arthroplasty fell 3 years after this procedure and subsequently incurred continuous pain in her buttock. Plain radiographs showed no fracture and no loosening of the hip prosthesis. Magnetic resonance imaging revealed an abnormal, large, thick-walled mass with heterogeneous signal intensity at the right buttock. The prerevision diagnosis was adverse reaction to metal debris. The mass was surgically resected, and the metal femoral head was replaced by a dual-mobility prosthesis. The intraoperative and histological analyses indicated an expanding hematoma. Cobalt ion concentrations of whole blood and effusion around the hematoma-1.9 µg/L and 1.3 µg/L, respectively-were not indicative of adverse reaction to metal debris. Transcatheter arterial embolization was performed 2 days postoperatively. The hematoma was reduced and was not present after 9 months. The diagnosis of a periprosthetic soft tissue mass after metal-on-metal total hip arthroplasty should be carefully reached with magnetic resonance imaging and assessment of blood metal ion concentrations. Expanding hematoma should be considered a potential diagnosis if metal ion concentrations are not increasing and magnetic resonance imaging shows a periprosthetic mass with a heterogeneous lesion. Embolization is useful for the management of an expanding hematoma. [Orthopedics. 2017; 40(6):e1103-e1106.].

Computer-assisted spherical osteotomy with a curved-bladed Tuke Saw.

Techniques for spherical osteotomy, such as rotational acetabular osteotomy, can help orthopaedic surgeons correct bony deformities and remove spherical acetabular components. Curved chisels are used during a spherical osteotomy, but they require skill and have a potential risk of damaging blood vessels or nerves. In order to perform a precise, quick and safe spherical osteotomy, we have developed a novel computer-assisted surgical tool using a vibrating bone saw, the Tuke Saw, with a curved blade that operates under the guidance of an optical navigation system. In this study, the accuracy and ease of use of this curved-bladed Tuke Saw in spherical osteotomy were examined in comparison with the conventional curved chisel. Using these surgical tools, hemispherical osteotomies were performed on rectangular parallelepiped Sawbones blocks and rotational acetabular osteotomies were performed on cadaveric pelves. The distance error with the curved-bladed Tuke Saw was significantly smaller than that with the curved chisel, and the procedure time with the Tuke Saw was approximately half that with the chisel. It can thus be concluded that the curved-bladed Tuke Saw is more accurate and easier to use than the conventional curved chisel.

Antitumor Effects of Eribulin Mesylate in Gemcitabine-resistant Pancreatic Cancer Cell Lines.

BACKGROUND/AIM: One reason of poor survival rate of patients with pancreatic cancer is the development of chemoresistance. The aim of the present study was to investigate the effects of eribulin mesylate in gemcitabine-refractory advanced pancreatic cancer cell lines. MATERIALS AND METHODS: Three human pancreatic cancer cell lines (AsPC-1, Panc-1, and SUIT-2) and human pancreatic endoderm (hPE) cells were used to evaluate the antitumor effects of gemcitabine and eribulin mesylate. Cell viability after treatment of cells with different concentrations of gemcitabine and eribulin mesylate was evaluated using water-soluble tetrazolium salts (WST) assays; cytotoxic effects were evaluated on the basis of morphological changes to cells. RESULTS: Gemcitabine had no effect on cell viability of AsPC-1 nor Panc-1 cells, whereas gemcitabine reduced cell viability of SUIT-2 cells in a dose-dependent manner. Eribulin mesylate significantly reduced cell viability of both AsPC-1 and Panc-1 cells (p<0.001 and p=0.002, respectively), but had no effect on hPE cells. Microscopic examination of AsPC-1 and Panc-1 cells after treatment with eribulin mesylate revealed morphological changes that included cell shrinkage, membrane blebbing, and fragmentation of the cells after drug exposure, and these were concentration-dependent effects. CONCLUSION: The findings of the present study suggest that eribulin mesylate may be a promising potential anticancer drug for gemcitabine-refractory advanced pancreatic cancer.

Establishment of a new scirrhous gastric carcinoma cell line with microsatellite instability.

We report on the establishment of a new scirrhous gastric cancer cell line with microsatellite instability (MSI), designated OCUM-7. This cell line was derived from a primary scirrhous gastric carcinoma. The cells were floating and round shape in culture. Histologic findings of xenografted tumor obtained from OCUM-7 cells showed a poorly differentiated adenocarcinoma with medullary growth. DNA histograms of OCUM-7 cells showed an aneuploid pattern. MSI status of OCUM-7 was analyzed using 8 microsatellite markers. Five of 8 microsatellite loci showed a novel band shift, which demonstrated that OCUM-7 cells were MSI-high. MSI-positive cell lines established from a primary scirrhous gastric carcinoma have not been reported, while several reports of the establishment of a scirrhous gastric cancer cell line are available. OCUM-7 might be beneficial for analyzing the mechanisms of MSI in scirrhous gastric carcinoma.

Tranilast (N-3,4-dimethoxycinamoyl anthranilic acid): a novel inhibitor of invasion-stimulating interaction between gastric cancer cells and orthotopic fibroblasts.

BACKGROUND: Fibroblasts produce various cytokines that affect the invasion ability of cancer cells. We have previously reported that gastric fibroblasts play an important role in the metastatic process of gastric cancer. Tranilast is a clinical drug for inhibition of fibroblast growth. To develop a drug for cancer invasion, the effect of Tranilast on the invasion-stimulating interaction was examined. MATERIALS AND METHODS: The human gastric carcinoma cell line, OCUM-2D, and the gastric fibroblast cell line, NF-10, were used. The effect of Tranilast on the invasion ability of OCUM-2D cells with NF-10 cells was examined by invasion assay. RESULTS: The invasion ability of OCUM-2D cells was significantly increased by co-culturing with NF-10 cells (p < 0.01). Tranilast, at concentrations of more than 0.01 mM, significantly suppressed the invasion ability of OCUM-2D cells co-cultured with NF-10 cells. Tranilast decreased matrix metalloproteinase-2 (MMP-2) and transforming growth factor-beta 1 (TGF-beta 1) production from fibroblasts. TGF-beta 1 enhanced the MMP-2 production from fibroblasts. The invasion ability of gastric cancer cells was increased by MMP-2 and TGF-beta 1 from fibroblasts and this effect was inhibited by Tranilast, which decreased the MMP-2 and TGF-beta 1 production from fibroblasts. CONCLUSION: Tranilast may be a promising new drug for preventing the metastasis of gastric cancer.

Surgical tool alignment guidance by drawing two cross-sectional laser-beam planes.

Conventional surgical navigation requires for surgeons to move their sight and conscious off the surgical field when checking surgical tool's positions shown on the display panel. Since that takes high risks of surgical exposure possibilities to the patient's body, we propose a novel method for guiding surgical tool position and orientation directly in the surgical field by a laser beam. In our navigation procedure, two cross-sectional planar laser beams are emitted from the two laser devices attached onto both sides of an optical localizer, and show surgical tool's entry position on the patient's body surface and its orientation on the side face of the surgical tool. In the experiments, our method gave the surgeons precise and accurate surgical tool adjusting and showed the feasibility to apply to both of open and percutaneous surgeries.

Safety of autologous bone marrow-derived mesenchymal stem cell transplantation for cartilage repair in 41 patients with 45 joints followed for up to 11 years and 5 months.

Among autologous somatic stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) are the most widely used worldwide to repair not only mesenchymal tissues (bone, cartilage) but also many other kinds of tissues, including heart, skin, and liver. Autologous BMSCs are thought to be safe because of the absence of immunological reaction and disease transmission. However, it is possible that they will form tumours during long-term follow-up. In 1988, we transplanted autologous BMSCs to repair articular cartilage, which was the first such trial ever reported. Subsequently we performed this procedure in about 40 patients. Demonstration that neither partial infections nor tumours appeared in these patients provided strong evidence for the safety of autologous BMSC transplantation. Thus, in this study we checked these patients for tumour development and infections. Between January 1998 and November 2008, 41 patients received 45 transplantations. We checked their records until their last visit. We telephoned or mailed the patients who had not visited the clinics recently to establish whether there were any abnormalities in the operated joints. Neither tumours nor infections were observed between 5 and 137 (mean 75) months of follow-up. Autologous BMSC transplantation is a safe procedure and will be widely used around the world.

Tailor-made surgical guide based on rapid prototyping technique for cup insertion in total hip arthroplasty.

BACKGROUND: A surgical guide made by the rapid prototyping (RP) technique for cup insertion in total hip arthroplasty might be useful to avoid malalignment of the cup, which indicates postoperative complications. METHODS: To address this research question, we applied a RP-based guide to 24 patients with their CT images. We designed it to fit onto the acetabular edge and to insert a Kirschner wire (K-wire) which indicated a planned cup direction. We intraoperatively placed it on the acetabular edge, inserted the K-wire through the guide on the superior acetabulum and implanted the cup while observing the alignment of the K-wire. We also recorded the additional time needed to use the guide. RESULTS: The mean cup accuracy between planned and postoperative alignments was 2.8 degrees (SD = 2.1 degrees ) for abduction and 3.7 degrees (SD = 2.7 degrees ) for anteversion. The mean additional time was 3.5 (range 2-6) min. CONCLUSION: We can use this guide with acceptable accuracy and without consuming an excessive amount of time.

Computer-assisted preoperative planning for reduction of proximal femoral fracture using 3-D-CT data.

This paper describes procedures for repositioning calculations of fractured bone fragments using 3-D-computed tomography (CT), aimed at preoperative planning for computer-guided fracture reduction of the proximal femur. Fracture boundaries of the bone fragments, as "fracture lines (FLs)," and the mirror-transformed contralateral femur shape extracted from 3-D-CT were used for repositioning of the fragments. We first describe a method for extracting FLs based on 3-D curvature analysis and then formulate repositioning methods based on registration of bone fragments using the following three constraints: 1) contralateral (CL) femur shape; 2) FLs; and 3) both CL femur shape and fracture lines, as "both constraints". We performed experiments using CT datasets from five simulated and four real patients with proximal femoral fracture. We evaluated the rotation error in reposition calculations and the contact ratio between repositioned fragment boundaries, which are crucial for the recovery of proper functional axes and bone adhesion of fragments, respectively. Experimental results showed that good accuracy and stability were attainable when registration using both constraints was performed after registration using the fracture-line constraint. On average, 6.0 degrees +/-0.8 degrees in rotation error and 89%+/-3 % in contact ratio were obtained without providing precise initial values.

MRI-based surgical simulation of transtrochanteric rotational osteotomy for femoral head osteonecrosis.

Transtrochanteric rotational osteotomy (TRO) is one of the joint-preserving surgical treatments for osteonecrosis of the femoral head (ONFH). It can prevent collapse of the femoral head as necrotic lesions in the weight-bearing portion can be moved sufficiently to a less weight-bearing portion by anterior rotation, posterior rotation, or varus angulation. Patient selection and preoperative planning are important to determine indications for TRO. It has been reported that successful TRO requires at least 34% of the weight-bearing area supported by the intact part of the femoral head. However, this ratio is difficult to preoperatively quantify according to the rotation angle using conventional two-dimensional MR images or X-rays. Therefore, we developed a method of simulating TRO using three-dimensional (3D) models reconstructed from 3D MR images and applied it to serial patients with types C1 and C2 osteonecrosis at stage 1 or 2. The simulation visualized positional changes of the necrotic lesion in the weight-bearing area and enabled quantitation of the postoperative intact ratio. Our surgical simulation is useful for evaluating the postoperative intact ratio and for determining indications for TRO as well as the optimal angle of femoral head rotation and varus angulation.

A robot assisted hip fracture reduction with a navigation system.

A fracture reduction robot is described as assisting in safe and precise fracture reduction. The robot is connected with pins that are inserted into the patient's bone fragments, together with a customized jig. The robot has six degrees of freedom with high precision, so that precise fracture reduction can be conducted. The failsafe unit of the fracture reduction robot can mitigate excessive reduction force that may cause complications such as avascular necrosis. We have integrated the fracture reduction robot with a navigation system that tracks the relative position of the bone fragments and generates the reduction path. The integrated system is evaluated with the simulated fracture reduction of a hip fracture model (n = 8). Three-dimensional parameters related to the mechanical axis--the proximal femur angle, the distal femur angle, and the length of the mechanical axis--were evaluated by comparing the normal values with those after reduction; these average differences are 1.76 degrees , 0.28 degrees and 0.76mm, respectively. The automated fracture reduction feature makes it possible for medical staff to work at a distance from radiation sources; for patients, the integrated fracture reduction system has the potential to reduce fractures with high precision.