Tsunemitsu Soeda

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine

The liver and exocrine pancreas share a common structure, with functioning units (hepatic plates and pancreatic acini) connected to the ductal tree. Here we show that Sox9 is expressed throughout the biliary and pancreatic ductal epithelia, which are connected to the intestinal stem-cell zone. Cre-based lineage tracing showed that adult intestinal cells, hepatocytes and pancreatic acinar cells are supplied physiologically from Sox9-expressing progenitors. Combination of lineage analysis and hepatic injury experiments showed involvement of Sox9-positive precursors in liver regeneration. Embryonic pancreatic Sox9-expressing cells differentiate into all types of mature cells, but their capacity for endocrine differentiation diminishes shortly after birth, when endocrine cells detach from the epithelial lining of the ducts and form the islets of Langerhans. We observed a developmental switch in the hepatic progenitor cell type from Sox9-negative to Sox9-positive progenitors as the biliary tree develops. These results suggest interdependence between the structure and homeostasis of endodermal organs, with Sox9 expression being linked to progenitor status.

Wwp2 is essential for palatogenesis mediated by the interaction between Sox9 and mediator subunit 25.

Sox9 is a direct transcriptional activator of cartilage-specific extracellular matrix genes and has essential roles in chondrogenesis. Mutations in or around the SOX9 gene cause campomelic dysplasia or Pierre Robin Sequence. However, Sox9-dependent transcriptional control in chondrogenesis remains largely unknown. Here we identify Wwp2 as a direct target of Sox9. Wwp2 interacts physically with Sox9 and is associated with Sox9 transcriptional activity via its nuclear translocation. A yeast two-hybrid screen using a cDNA library reveals that Wwp2 interacts with Med25, a component of the Mediator complex. The positive regulation of Sox9 transcriptional activity by Wwp2 is mediated by the binding between Sox9 and Med25. In zebrafish, morpholino-mediated knockdown of either wwp2 or med25 induces palatal malformation, which is comparable to that in sox9 mutants. These results provide evidence that the regulatory interaction between Sox9, Wwp2 and Med25 defines the Sox9 transcriptional mechanisms of chondrogenesis in the forming palate.

Sox9-expressing precursors are the cellular origin of the cruciate ligament of the knee joint and the limb tendons

Sox9 expression defines cell progenitors in a variety of tissues during mouse embryogenesis. To establish a genetic tool for cell‐lineage tracing and gene‐function analysis, we generated mice in which the CreERT2 gene was targeted to the endogenous mouse Sox9 locus. In Sox9CreERT2/+;R26R embryos, tamoxifen activated Cre recombinase exclusively in Sox9‐expressing tissues. To determine the suitability of this mouse line for developmental stage‐specific gene recombination, we investigated the cellular origins of the cruciate ligaments of the knee joint and the limb tendons, in which precursor cells have not been defined. The cells in these tissues were labeled after tamoxifen treatment before or at the stage of chondrogenic mesenchymal condensation, indicating that ligament and tendon cells originated from Sox9‐expressing cells and that cell fate determination occurred at mesenchymal condensation. This mouse line is a valuable tool for the temporal genetic tracing of the progeny of, and inducible gene modification in Sox9‐expressing cells. genesis 48:635–644, 2010.

Risk Factors for Cage Retropulsion After Posterior Lumbar Interbody Fusion Analysis of 1070 Cases

Study Design. Single-center retrospective study. Objective. We examined the risk factors for cage retropulsion after posterior lumbar interbody fusion (PLIF) performed for patients with degenerative lumbar spinal diseases. Summary of Background Data. Although PLIF is a widely accepted procedure, problems remain regarding perioperative and postoperative complications. There are few reported studies identifying specific risk factors for cage retropulsion, one of the implant-related complications after PLIF, although several case reports have been published. Methods. Between April 2006 and July 2010, 1070 patients with various degenerative lumbar spinal diseases underwent single- or multilevel PLIF combined with posterolateral fusion, using posterior pedicle screw fixation and box-type cages. Their medical records and preoperative radiographs were reviewed and the factors influencing the incidence of cage retropulsion were analyzed. Results. There were 9 cases of cage retropulsion (7 men and 2 women; mean age, 68.2 yr), and it developed within 2 months after surgery in all cases. Five patients had low back pain or leg pain, 3 of whom required revision surgery. The mean fusion level was 3.9 (range, 2–5); in 6 of the 9 patients, the cage had migrated at L5/S, 2 at L4/5, and 1 at L3/4. All of the cages were inserted at the end disc level of multilevel fusion procedures. The disc heights and ranges of motion were significantly greater in patients with cage retropulsion, and patients with a pear-shaped disc space also showed a higher rate of cage retropulsion. Conclusion. These results indicate that PLIF at L5/S, a wide disc space with instability, multilevel fusion surgery, and a pear-shaped disc space on lateral radiographs are risk factors for cage retropulsion. The identification of these risk factors should allow us to avoid this complication, and the use of expandable cages is an effective option for such cases.

Extremely wide and asymmetric anterior decompression causes postoperative C5 palsy: an analysis of 32 patients with postoperative C5 palsy after anterior cervical decompression and fusion.

Study Design. Single-center retrospective study. Objective. We examined whether extremely wide and asymmetric anterior decompression causes postoperative C5 palsy. Summary of Background Data. Postoperative C5 palsy is a complication of cervical decompression surgery. We hypothesized that C5 palsy may be caused by nerve root impairment through extremely wide and asymmetric dural expansion due to unilateral predominant wide anterior decompression with concomitant C4–C5 foraminal stenosis. Methods. The study included 32 patients with postoperative C5 palsy from a cohort of 459 patients who underwent anterior cervical decompression and fusion at the C4–C5 disc level for cervical myelopathy. The 64 upper extremities were divided into 2 groups according to palsy side (n = 35) or nonpalsy side (n = 29). Also, to correlate radiological findings, 66 consecutive patients who underwent anterior cervical decompression and fusion without postoperative C5 palsy were selected as control. Results. In patients with C5 palsy, the unilateral decompression width on the palsy side was significantly larger than that on the nonpalsy side (8.63 vs. 6.92 mm, P = 0.0003). In addition, the decompression width was significantly larger (15.69 vs. 14.38 mm, P = 0.02), the diameter of the C4–C5 foramen was significantly smaller (2.73 vs. 3.24 mm, P = 0.0008), the anterior spinal cord shift was significantly smaller (0.14 vs. 0.73 mm, P< 0.0001), and significant decompression asymmetry (0.74 vs. 0.89, P = 0.0003) was present in the patients with C5 palsy compared with controls. Conclusion. Extremely wide and asymmetric decompression concomitant with pre-existing C4–C5 foraminal stenosis may cause postoperative C5 palsy. Our findings should be valuable for surgeons considering anterior cervical decompression and fusion that includes the C4–C5 level. Surgeons should consider restriction of the decompression width to less than 15 mm and avoiding asymmetric decompression to reduce the incidence of C5 palsy. Level of Evidence: 4STUDY DESIGN Single-center retrospective study. OBJECTIVE We examined whether extremely wide and asymmetric anterior decompression causes postoperative C5 palsy. SUMMARY OF BACKGROUND DATA Postoperative C5 palsy is a complication of cervical decompression surgery. We hypothesized that C5 palsy may be caused by nerve root impairment through extremely wide and asymmetric dural expansion due to unilateral predominant wide anterior decompression with concomitant C4-C5 foraminal stenosis. METHODS The study included 32 patients with postoperative C5 palsy from a cohort of 459 patients who underwent anterior cervical decompression and fusion at the C4-C5 disc level for cervical myelopathy. The 64 upper extremities were divided into 2 groups according to palsy side (n = 35) or nonpalsy side (n = 29). Also, to correlate radiological findings, 66 consecutive patients who underwent anterior cervical decompression and fusion without postoperative C5 palsy were selected as control. RESULTS In patients with C5 palsy, the unilateral decompression width on the palsy side was significantly larger than that on the nonpalsy side (8.63 vs. 6.92 mm, P = 0.0003). In addition, the decompression width was significantly larger (15.69 vs. 14.38 mm, P = 0.02), the diameter of the C4-C5 foramen was significantly smaller (2.73 vs. 3.24 mm, P = 0.0008), the anterior spinal cord shift was significantly smaller (0.14 vs. 0.73 mm, P< 0.0001), and significant decompression asymmetry (0.74 vs. 0.89, P = 0.0003) was present in the patients with C5 palsy compared with controls. CONCLUSION Extremely wide and asymmetric decompression concomitant with pre-existing C4-C5 foraminal stenosis may cause postoperative C5 palsy. Our findings should be valuable for surgeons considering anterior cervical decompression and fusion that includes the C4-C5 level. Surgeons should consider restriction of the decompression width to less than 15 mm and avoiding asymmetric decompression to reduce the incidence of C5 palsy.

Hybrid Decompression and Fixation Technique Versus Plated 3-vertebra Corpectomy for 4-segment Cervical Myelopathy: Analysis of 81 Cases With a Minimum 2-year Follow-up

Study Design:A retrospective comparative study. Objective:The purpose of this study was to compare the stability and outcomes of a hybrid technique with those of a 3-vertebra corpectomy in the management of 4-segment cervical myelopathy. Summary of Background Data:Patients with primarily ventral disease and loss of cervical lordosis are considered good candidates for anterior surgery. Cervical corpectomy is commonly performed in patients with multilevel cervical myelopathy. Corpectomies including >3 vertebraes entail an extremely high risk of reconstruction failure. To avoid the need to perform a 3-vertebra corpectomy, we use a hybrid decompression and fixation technique. This hybrid technique is a technique to obtain optimum decompression and fixation in patients with multilevel cervical myelopathy. Methods:A total of 81 patients with multilevel cervical myelopathy who underwent 4-segment cervical fixation with a minimum 2-year follow-up were included. Results:The hybrid technique involved combining a plated 2-vertebra corpectomy and single-level discectomy with stand-alone cage fixation. This technique was performed in 39 patients, and the plated 3-vertebra corpectomy was performed in 42 patients. Nine patients (21%) who underwent the plated 3-vertebra corpectomy were treated with halo immobilization, but no patient in the hybrid group required this treatment (P=0.002). There were fewer instances of reconstruction failure in the hybrid group than in the 3-vertebra corpectomy group (0% vs. 10%, respectively; P=0.048) and fewer instances of C5 palsy (3% vs. 17%, respectively; P <0.0001). The incidence of postoperative C5 palsy was 25% for C3–C5 corpectomy, 19% for C4–C6 corpectomy, and 11% for C4–C5 corpectomy+C6–C7 discectomy. Conclusions:The hybrid technique has the following advantages over 3-vertebra corpectomy for 4-segment cervical fixation: a shorter graft bone and plate are required; the fixed segment has greater initial stability; postoperative external immobilization is simplified; and the risk of reconstruction failure and postoperative C5 palsy is reduced markedly.

Sacral fracture after instrumented lumbosacral fusion: analysis of risk factors from spinopelvic parameters.

Study Design. Retrospective comparative study. Objective. To examine the incidence and characteristics of key spinopelvic parameters that are correlated with sacral fracture development after lumbosacral fusion. Summary of Background Data. Sacral fracture is a possible complication of instrumented lumbosacral fusion and this has recently been documented in the literature. Preoperative awareness of risk factors concerning spinopelvic parameters and sacral fracture may aid in surgical planning to prevent its occurrence. Methods. All patients who underwent instrumented lumbosacral fusion from L2 or above, between 2010 and 2011 at Gakkentoshi Hospital, were included. Results. A total of 116 patients (47 men and 69 women) were evaluated in this study. Average age at surgery was 71 years, and the average follow-up period was 19 months. The average number of fixed segments was 5, and the average time interval between index surgery and sacral fracture development was 42 days. Notably, sacral fractures were identified in 5 patients (4.3%), all of whom were women. We, therefore, compared the 2 groups of female patients (fracture group, n = 5 vs. nonfracture group, n = 64). The fracture group had a substantially higher mean pelvic incidence (PI) than the nonfracture group (72° ± 8° vs. 51° ± 12°, respectively, P < 0.01). The fracture group also had a larger postoperative lumbar lordosis (LL)–PI mismatch than the nonfracture group (−26° ± 7° vs. −7° ± 18°, respectively, P < 0.01). Conclusion. The current review of our patients informs appropriate preoperative planning in cases involving lumbosacral fusion for postmenopausal women with a high PI. Surgeons should plan to achieve large increases in LL to restore not only spinopelvic harmony but also to avoid postoperative sacral fracture. For such patients, because it is difficult to consistently achieve a sufficiently large LL, we recommend prophylactic iliosacral fixation to protect the sacrum. Level of Evidence: 4

Recurrent throwing fracture of the humerus in a baseball player : case report and review of the literature.

The powerful twisting of the humerus that occurs during throwing can lead to spiral fractures. Fractures of the humerus that occur during throwing, such as in baseball, are not uncommon and have been well described. Baseball is now an international sport and reports of baseballrelated injuries are increasing. However, recurrent fractures caused by throwing are rare. We present the case of a baseball player who sustained a spiral fracture of the humerus while pitching and then suffered a second throwing fracture after the first had healed.

Pedicle Screw Fluid Sign: An Indication on Magnetic Resonance Imaging of a Deep Infection After Posterior Spinal Instrumentation.

Study Design: A single-center case-referent study. Objective: To assess whether the “pedicle screw (PS) fluid sign” on magnetic resonance imaging (MRI) can be used to diagnose deep surgical site infection (SSI) after posterior spinal instrumentation (PSI). Summary of Background Data: MRI is a useful tool for the early diagnosis of a deep SSI. However, the diagnosis is frequently difficult with feverish patients with clear wounds after PSI because of artifacts from the metallic implants. There are no reports on MRI findings that are specific to a deep SSI after PSI. We found that fluid collection outside the head of the PS on an axial MRI scan (PS fluid sign) strongly suggested the possibility of an abscess. Methods: The SSI group comprised 17 patients with a deep SSI after posterior lumbar spinal instrumentation who had undergone an MRI examination at the onset of the SSI. The non-SSI group comprised 64 patients who had undergone posterior lumbar spinal instrumentation who did not develop an SSI and had an MRI examination within 4 weeks after surgery. The frequency of a positive PS fluid sign was compared between both groups. Results: The PS fluid sign had a sensitivity of 88.2%, specificity of 89.1%, positive predictive value of 68.1%, and negative predictive value of 96.6%. The 2 patients with a false-negative PS fluid sign in the SSI group had an infection at the disk into which the interbody cage had been inserted. Three of the 7 patients with a false-positive PS fluid sign in the non-SSI group had a dural tear during surgery. Conclusions: The PS fluid sign is a valuable tool for the early diagnosis of a deep SSI. The PS fluid sign is especially useful for diagnosing a deep SSI in difficult cases, such as feverish patients without wound discharge.

Catastrophic Dropped Head Syndrome Requiring Multiple Reconstruction Surgeries after Cervical Laminoplasty

Introduction Dropped head syndrome (DHS) after cervical laminoplasty (LAMP) is a rare complication, and no etiologies or surgical strategies have been reported. We present a patient who developed catastrophic DHS after LAMP despite having preoperative cervical lordosis that is known to be suitable for LAMP. We describe a hypothesis concerning the possible mechanism responsible for the DHS and a surgical strategy for relieving it. Case Report A 76-year-old woman underwent LAMP for cervical spondylotic myelopathy. She achieved satisfactory improvement of neurological symptoms immediately after surgery. However, her neurological symptoms began to gradually deteriorate. She exhibited a dropped head and complained of difficulty maintaining horizontal gaze. Postoperative images showed a focal cervical kyphotic deformity causing anterior shift of the head, and recurrence of spinal cord compression was observed. She underwent additional surgeries for three times, but none of them restored her to baseline status. Retrospectively, the preoperative loading axis of the head existed anteriorly, and she also had a high T1 slope because of rigid thoracic kyphosis. Her preoperative hyper cervical lordosis was compensation for the global spinal malalignment. After LAMP, in accordance with decreases in her cervical lordosis, her head shifted anteriorly. The abnormal lever arm acting on the neck put further stress on the neck extensors, and the overstretched neck extensors possibly no longer generated enough power to raise the head. Uncompensated very high T1 slope because of marked thoracic kyphosis plus invasion of the posterior extensor mechanism by LAMP may have contributed to her catastrophic DHS development. Conclusions In the treatment of cervical myelopathy, posterior decompression alone should be applied carefully to elderly patients with cervical sagittal imbalance even if they have apparent cervical lordosis. Once DHS occurs because of cervical sagittal imbalance, normalization of global spinal balance through corrective osteotomy may be indispensable for a successful outcome.