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Objectives Open reduction and internal fixation of both columns is considered the treatment of choice for displaced anterior column with posterior hemitransverse (ACPHT) fractures in non-geriatric patients. Plate fixation of one column combined with lag screw fixation of the other column allows to decrease operative time and approach-related morbidity compared to conventional both column plating. The aim of this biomechanical study was to evaluate whether single column plate plus other column lag screw fixation confers similar stability to both column plate fixation. Physiological loads were simulated using both the single-leg stance (SLS) as well as the sit-to-stand (STS) loading protocols. Methods A clinically relevant ACPHT fracture model was created using fourth-generation composite hemipelves. Fractures were stabilized with three different fixation constructs: (1) anterior column plate plus posterior column screw fixation (AP+PCS), posterior column plate plus anterior column screw fixation (PP+ACS) and anterior column plate plus posterior column plate fixation (AP+PP). Specimens were loaded from 50 to 750 N with a ramp of 100 N/s. Fracture gap motion (FGM) and relative interfragmentary rotation (RIFR) between the three main fracture fragments were assessed under loads of 750 N using an optical 3D measurement system. Results STS loading generally resulted in higher mean FGM and RIFR than STS loading in the AP+PCS and AP+PP groups, while no significant differences were found in the PP+ACS group. Compared to conventional both column plate fixation (AP+PP), PP+ACS displayed significantly higher FGM and RIFR between the iliac wing and the posterior column during SLS loading. No significant differences in FGM and RIFR were identified between the AP+PCS and the AP+PP group. Conclusion Overall, single column plate plus other column lag screw fixation conferred similar stability to conventional both column plate fixation. From a clinical point of view, AP+PCS appears to be the most attractive alternative to conventional AP+PP for internal fixation of ACPHT fractures.

Objective Preoperative planning of the starting point and safe trajectory for iliosacral screw (SI screw) fixation using CT scans for safe and accurate fluoroscopically controlled percutaneous SI screw placement. Indications Transalar and transforaminal sacral fractures. SI joint disruptions and fracture-dislocations. Non- or minimally displaced spinopelvic dissociation injuries. Contraindications Transiliac instabilities. Sacral fractures with neurological impairment requiring decompression. Relevant residual displacement after closed reduction attempts. Insufficient fluoroscopic visualization of the anatomical landmarks of the upper sacrum. Surgical technique Preoperative planning of the starting point and the safe screw trajectory using CT scans and two-dimensional multiplanar reformation tools. Fluoroscopically guided identification of the starting point using the lateral view according to preoperative planning. Advancing the guidewire under fluoroscopic control using inlet and outlet views according to the planned trajectory. Predrilling and placement of 6.5 mm cannulated screws. Postoperative management Weightbearing as tolerated using crutches. Immediate CT scan in case of postoperative neurological impairment. Generally no screw removal. Results Fifty-nine screws were placed in 34 patients using the described technique. There were 2 cases of screw malpositioning (anatomical landmarks inadequately identified and fluoroscopically controlled SI screw fixation should thus not have been performed at all; in a case with sacral dysmorphism, preoperative planning suggested a posterior and/or caudal S1 starting point, respectively, but intraoperatively, selection of a different starting point and screw trajectory resulted in screw malpositioning with iatrogenic L5 nerve palsy).

Aims The aim of this retrospective study was to compare the correction achieved using a convex pedicle screw technique and a low implant density achieved using periapical concave-sided screws and a high implant density. We hypothesized that there would be no difference in outcome between the two techniques. Methods We retrospectively analyzed a series of 51 patients with a thoracic adolescent idiopathic scoliosis. There were 26 patients in the convex pedicle screw group who had screws implanted periapically (Group 2) and a control group of 25 patients with bilateral pedicle screws (Group 1). The patients’ charts were reviewed and pre- and postoperative radiographs evaluated. Postoperative patient-reported outcome measures (PROMs) were recorded. Results The number of implants (14.5 vs 17.1) and the implant density (1.5 vs 1.9) were significantly lower in Group 2 (p < 0.001). Operating time was 27 minutes shorter in Group 2 than in Group 1, with a mean of 217 minutes (SD 50.5; 120 to 346). The duration of surgery per instrumented vertebra was reduced by 19% in Group 2 (p = 0.011). No statistical difference was found in the postoperative Cobb angle, vertebral rotation, the relative correction achieved, or postoperative PROMs. Conclusion Despite a lower implant density and achieving correction through a convex rod, surgical correction of the Cobb angle and vertebral body rotation was similar in both groups. Periapical pedicle screws and primary correction on the concave side do not seem to be mandatory in order to achieve good surgical results in idiopathic thoracic scoliosis. The operating time was shorter in the group with lower implant density. In conclusion, the technique provided good results and has the potential to reduce complications and costs. Cite this article: Bone Joint J 2021;103-B(3):536–541.

Introduction Open reduction and internal fixation is considered the gold standard of treatment for displaced acetabular fractures in younger patients. For elderly patients with osteoporotic bone quality, however, primary total hip arthroplasty (THA) with the advantage of immediate postoperative mobilization might be an option. The purpose of this study was to evaluate the clinical and radiological outcomes of surgical treatment of displaced osteoporotic acetabular fractures using the acetabular roof reinforcement plate (ARRP) combined with THA. Materials and methods Between 2009 and 2019, 84 patients were operated using the ARRP combined with THA. Inclusion criteria were displaced osteoporotic fractures of the acetabulum with or without previous hemi- or total hip arthroplasty, age above 65 years, and pre-injury ability to walk at least with use of a walking frame. Of the 84 patients, 59 could be followed up after 6 months clinically and radiographically. Forty-nine (83%) were primary fractures and 10 (17%) periprosthetic acetabular fractures. Results The mean age was 80.5 years (range 65–98 years). The average time from injury to surgery was 8.5 days (range 1–28). Mean time of surgery was 167 min (range 100–303 min). Immediate postoperative full weight bearing (FWB) was allowed for 51 patients (86%). At the 6-month follow-up, all 59 patients except one showed bony healing and incorporation of the ARRP. One case developed a non-union of the anterior column. No disruption, breakage or loosening of the ARRP was seen. Additional CT scans performed in 18 patients confirmed bony healing. Twenty-six patients (44%) had regained their pre-injury level of mobility. Complications requiring revision surgery occurred in 8 patients. Five of them were suffering from a prosthetic head dislocation, one from infection, one from hematoma and one from a heterotopic ossification. Conclusions The ARRP has proven to provide sufficient primary stability to allow for immediate FWB in most cases and represents a valuable option for the surgical management of displaced acetabular fractures in this challenging patient group.

Background Cement augmentation of pedicle screws to prevent screw loosening is associated with significant complications, such as cement leakage or bone necrosis. Therefore, an alternative strategy to improve pedicle screw anchorage has been recently developed: Polymer reinforcement of pedicle screws uses an in situ melted polymer sleeve in order to enhance screw anchorage. This biomechanical study evaluated the effect of polymer-reinforcement by comparing polymer-reinforced pedicle screws to non-augmented as well as cement-augmented screws under cyclic loading. Methods For each of the two comparisons (polymer-reinforced vs. non-augmented screws and polymer-reinforced vs. cement-augmented screws), polymer-reinforced screws and control screws were placed into the left and right pedicle of seven vertebrae (mean age: 74.0 (SD 9.3) years) to allow for pairwise left–right comparisons. Each screw was subjected to cyclic cranio-caudal loading with an initial load ranging from −50 N to +50 N and with stepwise increasing compressive loads (5 N every 100 cycles) until screw loosening. Findings Polymer-reinforced pedicle screws resisted a higher number of load cycles until loosening than the contralateral non-augmented control screws (4300 SD 2018 vs. 2457 SD 1116 load cycles, p = 0.015). Screw anchorage of polymer-reinforced pedicle screws was comparable to that of cement augmented control screws (3857 (SD2085) vs. 4300 (SD1257) load cycles until failure, p = 0.64). Interpretation Our findings indicate that polymer-reinforcement significantly enhances pedicle screw anchorage in low quality bone and that its effect is similar in size than that of cement augmentation.

Introduction Nonunion is a common complication after intramedullary nailing of subtrochanteric femoral fractures. A more detailed knowledge, particularly of avoidable risk factors for subtrochanteric fracture nonunion, is thus desired to develop strategies for reducing nonunion rates. The aim of the present study therefore was to analyse a wide range of parameters as potential risk factors for nonunion after intramedullary nailing of subtrochanteric fractures. Materials and methods Seventy-four patients who sustained a subtrochanteric fracture and were treated by femoral intramedullary nailing at a single level 1 trauma centre within a 6-year period were included in this study. A total of 15 patient-related, fracture-related, surgery-related, mechanical and biological parameters were analysed as potential risk factors for nonunion. Furthermore, the accuracy of each of these parameters to predict nonunion was calculated. Results Nonunion occurred in 17 of 74 patients (23.0%). Of the 15 potential risk factors analysed, only 3 were found to have a significant effect on the nonunion rate (p 0.70. Furthermore, the nonunion rate significantly increased with the number of risk factors (no risk factor: 2.9%, one risk factor: 23.8%, two risk factors: 52.9%, and three risk factors: 100% [Chi-square test, p = 0.001)]. Conclusions Our study indicates that intraoperative correction of varus malalignment and restoration of the medial cortical support are the most critical factors to prevent nonunion after intramedullary nailing of subtrochanteric femoral fractures. In addition, autodynamisation of the nail within the first 3 months post-surgery is a strong predictor for failure and should result in revision surgery.

Introduction The classification and management of osteoporotic pelvic ring injuries (OPRI) remain challenging. The fragility fractures of the pelvis (FFP) classification system proposed by Rommens and Hofmann constitutes the first comprehensive classification system of OPRI and may contribute to a more thorough assessment and grading of these injuries. The reliability of the FFP classification system, however, has not been evaluated yet. The purpose of this study therefore was to determine the inter- and intraobserver reliability of the FFP classification system and to critically analyse its strengths and weaknesses. Materials and methods One-hundred pelvic CT scans obtained from a consecutive series of patients aged 70 years and older who sustained a low-energy pelvic ring injury were included in this study. Three orthopaedic traumatologists of varying levels of experience (one experienced pelvic surgeon, one consultant, one resident) and one musculoskeletal radiologist independently classified each OPRI according to the FFP classification in two different sessions. Intra- and interobserver reliability were determined using percentage agreement and Cohen’s Kappa coefficients. Results The observed relative distribution of FFP fracture types was comparable to that reported in the original study by Rommens and Hofmann. Overall interobserver reliability for all 100 cases was moderate with Kappa values from 0.42 to 0.59 (mean percentage agreement: 61% (54%–68%)), while intraobserver reliability was substantial with Kappa values from 0.68 to 0.72 (mean percentage agreement: 77% (76%–78%)). Subgroup analysis revealed lowest reliability for the classification of Type IIc, IIIc and IVb injuries (32 cases). Within this subgroup of combined anterior and posterior OPRI involving a complete nondisplaced or displaced (uni- or bilateral) sacral fracture, Kappa values for interobserver reliability ranged from 0.10 to 0.52, while those for intraobserver reliability ranged from 0.29 to 0.66. Conclusion Overall interobserver reliability of the FFP classification system was moderate, while intraobserver reliability was substantial. Despite the acceptable overall reliability, classification of FFP subtypes involving a complete nondisplaced or displaced sacral fracture showed relatively poor reliability. The latter limits the usefulness of the FFP classification for both clinical and research purposes and needs to be addressed in future studies.

Objectives To biomechanically compare five different fixation techniques for transverse acetabular fractures using both the single-leg stance (SLS) and the sit-to-stand (STS) loading protocols and to directly compare fracture gap motion (FGM) and relative interfragmentary rotation (RIFR). Methods Transtectal transverse acetabular fractures were created on fourth-generation composite hemipelves in a reproducible manner. Five different fixation techniques were biomechanically assessed using both an SLS and STS loading protocol: anterior plate (AP) only, posterior plate (PP) only, anterior plate plus posterior column screw (AP+PCS), posterior plate plus anterior column screw (PP+ACS) and anterior plus posterior plate (AP+PP). After preconditioning, the specimens were loaded from 50 to 750 N with a ramp of 100 N/s. FGM and RIFR under loads of 750 N were measured using an optical 3D measurement system. Results In the three groups of fixation techniques addressing both columns, STS loading resulted in higher mean FGM and in RIFR than SLS loading. No construct failure was observed. In the single plate groups (AP only and PP only), STS loading resulted in failure of all specimens before reaching loads of 750 N, while no failure occurred after SLS loading. No significant differences in FGM and RIFR were found between the double plate (AP+PP) and the single plate plus column screw (AP+PCS and PP+ACS) techniques. Conclusion SLS loading appeared to overestimate the strength of acetabular fracture fixation constructs and STS loading may be more appropriate to provide clinically relevant biomechanical data. Internal fixation of a single column might not provide adequate stability for transverse fractures, while strength of single plate plus column screw fixation and double plate fixation was comparable.

Introduction In combined posterior–anterior stabilization of thoracolumbar burst fractures, the expandable vertebral body replacement device (VBRD) is typically placed bisegmentally for anterior column reconstruction (ACR). The aim of this study, however, was to assess feasibility, outcome and potential pitfalls of monosegmental ACR using a VBRD. In addition, clinical and radiological outcome of monosegmental ACR was related to that of bisegmental ACR using the same thoracoscopic technique. Methods Thirty-seven consecutive neurologically intact patients with burst fractures of the thoracolumbar junction (T11–L2) treated by combined posterior–anterior stabilization were included. Monosegmental ACR was performed in 18 and bisegmental ACR in 19 patients. Fracture type and extent of vertebral body comminution were determined on preoperative CT scans. Monosegmental and bisegmental kyphosis angles were analyzed preoperatively, postoperatively and at final radiological follow-up. Clinical outcome was assessed after a minimum of 2 years (74 ± 45 months; range 24–154; follow-up rate 89.2%) using VAS Spine Score, RMDQ, ODI and WHOQOL-BREF. Results Monosegmental ACR resulted in a mean monosegmental and bisegmental surgical correction of − 15.6 ± 7.7° and − 14.7 ± 8.1°, respectively. Postoperative monosegmental and bisegmental loss of correction averaged 2.7 ± 2.7° and 5.2 ± 3.7°, respectively. Two surgical pitfalls of monosegmental ACR were identified: VBRD positioning (1) onto the weak cancellous bone (too far cranially to the inferior endplate of the fractured vertebra) and (2) onto a significantly compromised inferior endplate with at least two (even subtle) fracture lines. Ignoring these pitfalls resulted in VBRD subsidence in five cases. When relating the clinical and radiological outcome of monosegmental ACR to that of bisegmental ACR, no significant differences were found, except for frequency of VBRD subsidence (5 vs. 0, P = 0.02) and bisegmental loss of correction (5.2 ± 3.7° vs. 2.6 ± 2.5°, P = 0.022). After exclusion of cases with VBRD subsidence, the latter did not reach significance anymore (4.9 ± 4.0° vs. 2.6 ± 2.5°, P = 0.084). Conclusions This study indicates that monosegmental ACR using a VBRD is feasible in thoracolumbar burst fractures if the inferior endplate is intact (incomplete burst fractures) or features only a single simple split fracture line (burst-split fractures). If the two identified pitfalls are avoided, monosegmental ACR may be a viable alternative to bisegmental ACR in selected thoracolumbar burst fractures to spare a motion segment and to reduce the distance for bony fusion.

Pedicle screw loosening is a common and significant complication after posterior spinal instrumentation, particularly in osteoporosis. Radiolucent carbon fiber-reinforced polyetheretherketone (CF/PEEK) pedicle screws have been developed recently to overcome drawbacks of conventional metallic screws, such as metal-induced imaging artifacts and interference with postoperative radiotherapy. Beyond radiolucency, CF/PEEK may also be advantageous over standard titanium in terms of pedicle screw loosening due to its unique material properties. However, screw anchorage and loosening of CF/PEEK pedicle screws have not been evaluated yet. The aim of this biomechanical study therefore was to evaluate whether the use of this alternative nonmetallic pedicle screw material affects screw loosening. The hypotheses tested were that (1) nonmetallic CF/PEEK pedicle screws resist an equal or higher number of load cycles until loosening than standard titanium screws and that (2) PMMA cement augmentation further increases the number of load cycles until loosening of CF/PEEK screws. In the first part of the study, left and right pedicles of ten cadaveric lumbar vertebrae (BMD 70.8 mg/cm3 ± 14.5) were randomly instrumented with either CF/PEEK or standard titanium pedicle screws. In the second part, left and right pedicles of ten vertebrae (BMD 56.3 mg/cm3 ± 15.8) were randomly instrumented with either PMMA-augmented or nonaugmented CF/PEEK pedicle screws. Each pedicle screw was subjected to cyclic cranio-caudal loading (initial load ranging from − 50 N to + 50 N) with stepwise increasing compressive loads (5 N every 100 cycles) until loosening or a maximum of 10,000 cycles. Angular screw motion (“screw toggling”) within the vertebra was measured with a 3D motion analysis system every 100 cycles and by stress fluoroscopy every 500 cycles. The nonmetallic CF/PEEK pedicle screws resisted a similar number of load cycles until loosening as the contralateral standard titanium screws (3701 ± 1228 vs. 3751 ± 1614 load cycles, p = 0.89). PMMA cement augmentation of CF/PEEK pedicle screws furthermore significantly increased the mean number of load cycles until loosening by 1.63-fold (5100 ± 1933 in augmented vs. 3130 ± 2132 in nonaugmented CF/PEEK screws, p = 0.015). In addition, angular screw motion assessed by stress fluoroscopy was significantly smaller in augmented than in nonaugmented CF/PEEK screws before as well as after failure. Using nonmetallic CF/PEEK instead of standard titanium as pedicle screw material did not affect screw loosening in the chosen test setup, whereas cement augmentation enhanced screw anchorage of CF/PEEK screws. While comparable to titanium screws in terms of screw loosening, radiolucent CF/PEEK pedicle screws offer the significant advantage of not interfering with postoperative imaging and radiotherapy. These slides can be retrieved under Electronic Supplementary Material.

Introduction Straight antegrade humeral nailing (SAHN) has become a standard technique for the surgical fixation of proximal humeral fractures, which predominantly affect elderly females. The nail’s proximal anchoring point has been demonstrated to be critical to ensure reliable fixation in osteoporotic bone and to prevent iatrogenic damage to the superior rotator cuff bony insertion. Anatomical variations of the proximal humerus, however, may preclude satisfactory anchoring of the nail’s proximal end and may bare the risk of rotator cuff violation, even though the nail is inserted as recommended. The aim of this study was to evaluate the anatomical suitability of proximal humeri of geriatric females aged 75 years and older for SAHN. Specifically, we sought to assess the proportion of humeri not anatomically amenable to SAHN for proximal humeral fracture. Materials and Methods A total of 303 proximal humeri of 241 females aged 75 years and older (mean age 84.5 ± 5.0 years; range 75–102 years) were analyzed for this study. Multiplanar two-dimensional reformations (true ap, true lateral, and axial) were reconstructed from shoulder computed tomography (CT) data sets. The straight antegrade nail’s ideal entry point, “critical point” (CP), and critical distance (CD; distance between ideal entry point and CP) were determined. The rate of proximal humeri not anatomically suitable for SAHN (critical type) was assessed regarding proximal reaming diameters of currently available straight antegrade humeral nails. Results Overall, 35.6% (108/303) of all proximal humeri were found to be “critical types” (CD

Introduction Classification and management of osteoporotic pelvic ring injuries (OPRI) continue to pose a considerable challenge to orthopaedic traumatologists. The currently used fragility fractures of the pelvis (FFP) classification of OPRI has recently been shown to have significant weaknesses. The aim of this study therefore was to propose a new, simple, yet comprehensive alphanumeric classification (ANC) of OPRI and to assess its intra- and interobserver reliability. Furthermore, its potential advantages over the FFP classification are discussed. Materials and methods One hundred consecutive CT scans from patients with OPRI were evaluated by three orthopaedic traumatologists with varying levels of experience and one musculoskeletal radiologist. Intra- and interobserver reliability of the proposed classification system was assessed using weighted kappa (κ) statistics and percentage agreement. In addition, the Fleiss’ kappa statistic was computed to assess interobserver agreement among all four raters. Results Overall intraobserver reliability of the proposed ANC was substantial [κ ranging from 0.71 to 0.80; percentage agreement: 70% (range, 67–76%)]. Overall interobserver reliability between pairs of raters was substantial as well [κ ranging from 0.61 to 0.68; percentage agreement: 58% (range, 53–61%)]. For ANC types, groups and subgroups, intra- and interobserver reliability were substantial to almost perfect. Interobserver agreement among all four raters was moderate to substantial, with Fleiss’ kappa values of 0.48, 0.69, 0.71 and 0.52 for ANC overall, types, groups and subgroups, respectively. Conclusion The proposed ANC of OPRI demonstrated overall reliability comparable to that of the FFP classification. The ANC, however, is simple, more comprehensive, and consistently relates to injury severity.

Background Severe acetabular bone loss is often treated with reconstruction cages and impaction grafting using allograft bone. Accurate implant positioning is crucial for successful clinical and radiological outcomes. The direct anterior approach (DAA) is a standard approach for primary total hip arthroplasty (THA) that is being used more frequently for revision THA. The aim of this study was to report midterm clinical and radiological outcomes of acetabular revision arthroplasty using the DAA to address large acetabular defects by using a reconstruction cage and impaction grafting. Methods Acetabular cup revisions were performed in 64 patients (64 hips) with severe acetabular bone loss. All patients received reconstruction cages with impaction grafting via the DAA. The stem was also revised in 22 patients. Complications, radiological, and functional outcomes were assessed. Results Six of the 64 patients were revised at a mean follow-up of 27.6 months (range, 11-84 months), two each for implant failure, infection, and recurrent dislocation. One hip showed the radiological failure of the implant, but the patient was asymptomatic and was not revised. The median Western Ontario McMasters Osteoarthritis Score (WOMAC) for the cohort overall improved significantly (P Conclusion Good midterm outcomes can be obtained with the DAA for acetabular cup revisions done to address severe acetabular bone loss by using reconstruction cages and impaction grafting. The number of complications was within the expected range for this type of revision procedure at midterm follow-up, and dislocation rates were low.

The aim of this study was to compare the effects of sequestrectomy versus conventional microdiscectomy on breaking response time (BRT) for lumbar disc herniation (LDH). BRT is the key factor for return to drive recommendations after surgery. A prospective clinical study was conducted. Patients aged 25–65 years who underwent surgery for lumbar disc herniation and held a valid motorcar driving license were recruited in a single institution. The patients were assessed before surgery, immediately after the surgery and at the follow up examination 30 days post-surgery. BRT was measured using a driving simulator, a visual analogue scale (VAS) was used for pain assessment. BRT values were compared with BRT values of a healthy control group. In patients treated with microdiscectomy BRT reduced from 749 (±223) msec before surgery to 649 (±223) msec immediately after the surgery. In the sequestrectomy group BRT reduced from 852 (±561) msec before surgery to 693 (±173) msec immediately after the surgery. BRT at follow up was 610 (±145) msec for patients treated with microdiscectomy and 630 (±98) msec for patients operated with sequestrectomy. BRT for healthy controls was 487 (±116) msec. Pain improved significantly for both patient samples. Sequestrectomy and microdiscectomy were associated with similar effects on pain and BRT after surgery. There was no statistically significant difference between BRT of both patient samples at 30 days follow up examination. Both surgical techniques showed a positive effect on BRT. No statistically significant difference between sequestrectomy and microdiscectomy on BRT could be found.

Introduction The aim of this study was to evaluate results of surgical stabilisation of hyperextension injuries of the thoracolumbar spine in patients with ankylosing spinal disorders using two different treatment strategies: the conventional open rigid posterior instrumentation and percutaneous less rigid posterior instrumentation. Surgical and non-surgical complications, the postoperative radiological course, and clinical outcome at final follow-up were comparatively assessed. Moreover, we sought to discuss important biomechanical and surgical aspects specific to posterior instrumentation of the ankylosed thoracolumbar spine as well as to elaborate on the advantages and limitations of the proposed new treatment strategy involving percutaneous less rigid stabilisation and fracture reduction by postoperative mobilisation. Materials and methods Between January 2006 and June 2012, a consecutive series of 20 patients were included in the study. Posterior instrumentation was performed either using an open approach with rigid 6.0 mm bars (open rigid (OR) group) or via a percutaneous approach using softer 5.5 mm bars (percutaneous less rigid (PLR) group). Complications as well as the radiological course were retrospectively assessed, and patient outcome was evaluated at final follow-up using validated outcome scores (VAS Spine Score, ODI, RMDQ, Parker Mobility Score, Barthel Score and WHOQOL-BREF). Results Surgical complications occurred more frequently in the OR group requiring revision surgery in two patients, while there was no revision surgery in the PLR group. The rate of postoperative complications was lower in the PLR group as well (0.7 vs. 1.3 complications per patient, respectively). Fracture reduction and restoration of pre-injury sagittal alignment by postoperative mobilisation occurred within the first 3 weeks in the PLR group, and within 6 months in the OR group. The clinical outcome at final follow-up was very good in both groups with no relevant loss in VAS Spine Score (pain and function), Parker Mobility Score (mobility), and Barthel Index (social independency) compared to pre-operative values. Conclusions This study indicates that the proposed treatment concept involving percutaneous less rigid posterior instrumentation and fracture reduction by postoperative mobilisation is feasible, seems to facilitate adequate reduction and restoration of pre-injury sagittal alignment, and might have the potential to reduce the rate of complications in the management of hyperextension injuries of the ankylosed thoracolumbar spine.

Background Percutaneous sacroiliac screw fixation under fluoroscopic control is an effective method for posterior pelvic ring stabilization. However, sacral dysmorphism has a high risk of L5 nerve injury. This study describes a simple method for the preoperative assessment of the sacral morphology using CT scans with widely available tools. Materials and methods CT scans of 1000 patients were analyzed. True inlet, outlet, and lateral views of the sacrum were obtained using a two-dimensional reconstruction tool to align the sacrum in a reproducible manner. Corridor morphology in the inlet view was measured to calculate different morphological types: (1) Ascending type, (2) Horizontal type, and (3) Descending type. In a second step, the corridor was analyzed for the presence of an anterior indentation of the sacrum between the SI joint and the midsagittal plane with proximity to the nerve root L5, which, therefore, may be harmed during screw misplacement. Results A notch was found in the majority of cases with relative frequencies ranging from 69 % (upper quartile of S1) to 95 % (upper quartile of S2). Descending types were, by far, the most frequent corridor type with one exception: In the upper quartile of S1, the ascending type was the most frequent corridor (71 %). Horizontal types were less frequent with a relative incidence between 2 and 14 %. Discussion This study should increase the awareness for sacral dysmorphism, emphasize the importance of a preoperative assessment of the osseous corridor, and provide a simple method for the preoperative assessment with widely available tools.

Objective Safe posterior column screw fixation via an anterior approach under two-dimensional fluoroscopic control. Indications Anterior column with posterior hemitransverse fractures (ACPHF); transverse fractures; two-column fractures and T‑type fractures without relevant residual displacement of the posterior column after reduction of the anterior column and the quadrilateral plate. Contraindication Acetabular fractures requiring direct open reduction via a posterior approach; very narrow osseous corridor in preoperative planning; insufficient intraoperative fluoroscopic visualization of the anatomical landmarks. Surgical technique Preoperative planning of the starting point and screw trajectory using a standard pelvic CT scan and a multiplanar reconstruction tool. Intraoperative fluoroscopically controlled identification of the starting point using the anterior–posterior (ap) view. Advancing the guidewire under fluoroscopic control using the lateral–oblique view. Lag screw fixation of the posterior column with cannulated screws. Postoperative management Partial weight bearing as advised by the surgeon. Postoperative CT scan for the assessment of screw position and quality of reduction of the posterior column. Generally no implant removal. Results In a series of 100 pelvic CT scans, the mean posterior angle of the ideal posterior column screw trajectory was 28.0° (range 11.1–46.2°) to the coronal plane and the mean medial angle was 21.6° (range 8.0–35.0°) to the sagittal plane. The maximum screw length was 106.3 mm (range 82.1–135.0 mm). Twelve patients were included in this study: 10 ACPHF and 2 transverse fractures. The residual maximum displacement of the posterior column fracture component in the postoperative CT scan was 1.4 mm (0–4 mm). There was one intraarticular screw penetration and one perforation of the cortical bone in the transition zone between the posterior column and the sciatic tuber without neurological impairment.

To revisit the concept of spondylotic traumatic central cord syndrome (TCCS) by assessing the frequency of discoligamentous injury and to correlate magnetic resonance imaging (MRI) and intraoperative findings. A retrospective analysis of twenty-three consecutive patients (mean age: 62.7 ± 14.8 years) with profound spondylotic TCCS after acute cervical hyperextension trauma but without signs of instability on initial CT scans who underwent anterior surgical decompression and fusion was performed. Sensitivity and specificity of MRI in the detection of anterior longitudinal ligament disruption were calculated. The topographic relations between surgically verified segmental instabilities and spinal cord signals on MRI were analyzed. The cervical MRI scans of all patients were evaluated by the radiologist on call at time of admission, re-assessed by a specialized MRI radiologist for the purpose of this study and compared with intraoperative findings. Intraoperative findings revealed 25 cervical spine segments with hyperextension instability in 22 of 23 (95.7%) patients. The radiologist on call correctly assessed segmental hyperextension instability in 15 of 25 segments (sensitivity: 0.60, specificity: 1.00), while the specialized MRI radiologist was correct in 22 segments (sensitivity: 0.88, specificity: 1.00). In 17 of 23 (73.9%) patients, the level of spinal cord signal on MRI matched the level of surgically verified segmental instability. Our findings challenge the traditional concept of spondylotic TCCS as an incomplete cervical spinal cord injury without discoligamentous injury and emphasize the importance of MRI as well as the radiologist’s level of experience for the assessment of segmental instability in these patients. These slides can be retrieved under Electronic Supplementary Material.

Tumor grade is a traditional prognostic parameter in colorectal cancer. Remarkably, however, there is still no generally accepted consensus how to perform tumor grading. In this study, we systematically compared the prognostic value of traditional grading based upon histological features, that is, gland formation alone with grading based upon both histological and cytological features, such as nuclear pleomorphism and anaplasia (“alternative grade”). Three hundred eighty-one tumors of randomly selected patients were retrospectively reviewed. Traditional and alternative tumor grades were related to various clinicopathological features and to progression-free and cancer-specific survival applying both univariate and multivariate testing. Traditional and alternative tumor grades were significantly associated with T and N classification, tumor size, lymphovascular invasion, as well as both progression-free and cancer-specific survival. In Cox’s proportional hazards regression models, the alternative grade was superior to the traditional tumor grade and was significantly associated with progression-free survival (hazard ratio 1.57, 95 % confidence interval 1.04–2.35; p = 0.031), independent of patients’ age and gender, T and N classification, and lymphovascular invasion. Likewise, patients with tumors with high alternative grade were more likely to die of disease (hazard ratio 1.30, 95 % confidence interval 0.85–2.00), but this difference was not statistically significant (p = 0.22). Tumor grade based upon both histological and cytological features was superior to grade based upon histological features alone and proved to be an independent prognostic parameter. Thus, tumor grade based upon both histological and cytological features may help to improve prognostic stratification and may thereby affect clinical decision-making and patient management.

Behandlung groser dia- und metaphysarer Knochendefekte (> 3 cm) in zwei operativen Eingriffen mit einem zeitlichen Abstand von 4–8 Wochen. Dia- und metaphysare Knochendefekte vorwiegend am Unter- und Oberschenkel. Knochendefekte mit Gelenkbeteiligung, persistierender Knocheninfekt oder Osteomyelitis, insuffiziente Weichteildeckung im Bereich des Knochendefekts, Osteoporose. Ersteingriff: Ausgiebiges Knochendebridement und Weichteildeckung, Einbringen eines Zementspacers in den Knochendefekt zur Induktion einer synovialen Fremdkorpermembran, interne oder externe Stabilisierung. Zweiteingriff: Entfernen des Zementspacers und Fullung des von der induzierten Membran umgebenen Knochendefekts mit autologer Spongiosa, ggf. Verfahrenswechsel auf eine interne Fixation. Schmerzabhangige Teil- bis Vollbelastung nach dem Ersteingriff. Abrollende Mobilisation nach dem Zweiteingriff bis zum Auftreten von radiologischen Zeichen eines Remodellings des Regenerats. In der Regel Belassen des Implantats. Insgesamt wurden 6 Patienten (4 Manner, 2 Frauen) im Alter von 15–66 Jahren mit Knochendefekten von durchschnittlich 7 cm (Spanne 4–10 cm) mit der Masquelet-Technik behandelt. Es handelte sich um 2 femorale aseptische Pseudarthrosen und 4 tibiale Pseudarthrosen (je 2 septische und aseptische Pseudarthrosen), dabei in einem Fall um eine periprothetische Pseudarthrose an der Tibia bei schaftgefuhrter Knieprothese. Die Stabilisierung nach Debridement erfolgte an der Tibia in allen Fallen zunachst mit einem Ringfixateur, am Femur einmal mit einem Marknagel und einmal mit einer winkelstabilen Platte. Der Zweiteingriff wurde zwischen 6 und 9 Wochen nach dem Ersteingriff durchgefuhrt. Dabei wurde in 3 von 4 Fallen an der Tibia ein Verfahrenswechsel auf eine interne Fixation durchgefuhrt. Die Spongiosa wurde entweder vom Beckenkamm oder in RIA-Technik („Reamer-Irrigator-Aspirator“) entnommen. Bei der Patientin mit dem periprothetischen Knochendefekt kam es nach 5 Monaten zu einem Plattenbruch und konsekutiver Unterschenkelamputation. In einem Fall wurde aufgrund einer Pseudarthrose an der Andockstelle eine lokale Spongiosaplastik durchgefuhrt. Alle Patienten waren nach 6 Monaten schmerzfrei und vollbelastend mobil. Der Ilizarov-Fixateur konnte bei einem 15-jahrigen Patienten 5 Monate nach dem Zweiteingriff entfernt werden. Die restlichen Implantate wurden belassen.

Spinal injuries are common and potentially devastating injuries. The thoracolumbar spine constitutes the most common site of spinal injuries. Depending on the mechanism of injury as well as the predominant forces and moments acting on the spine at the time of injury, typical thoracolumbar injury patterns result. The wide spectrum of thoracolumbar injuries is classified according to the AOSpine thoracolumbar spine injury classification system and varies from insignificant transverse process fractures to multidirectionally unstable injuries with complete spinal cord injury. Treatment options range from conservative to combined posteroanterior stabilization depending on the specific injury pattern. Posterior-only fixations using pedicle screw/rod constructs are most widely used to realign and stabilize the injured thoracolumbar spine. However, in thoracolumbar injuries with severe anterior column compromise, combined posteroanterior stabilization represents the treatment of choice.

Percutaneous sacroiliac screw fixation under fluoroscopic control is an effective method for posterior pelvic ring stabilization. However, sacral dysmorphism has a high risk of L5 nerve injury. This study describes a simple method for the preoperative assessment of the sacral morphology using CT scans with widely available tools.CT scans of 1000 patients were analyzed. True inlet, outlet, and lateral views of the sacrum were obtained using a two-dimensional reconstruction tool to align the sacrum in a reproducible manner. Corridor morphology in the inlet view was measured to calculate different morphological types: (1) Ascending type, (2) Horizontal type, and (3) Descending type. In a second step, the corridor was analyzed for the presence of an anterior indentation of the sacrum between the SI joint and the midsagittal plane with proximity to the nerve root L5, which, therefore, may be harmed during screw misplacement.A notch was found in the majority of cases with relative frequencies ranging from 69 % (upper quartile of S1) to 95 % (upper quartile of S2). Descending types were, by far, the most frequent corridor type with one exception: In the upper quartile of S1, the ascending type was the most frequent corridor (71 %). Horizontal types were less frequent with a relative incidence between 2 and 14 %.This study should increase the awareness for sacral dysmorphism, emphasize the importance of a preoperative assessment of the osseous corridor, and provide a simple method for the preoperative assessment with widely available tools.

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. Peri- and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Tumors were diagnosed in American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I in 21%, stage II in 32%, stage III in 33%, and stage IV in 14%. Presence and extent of eosinophils was related to various histopathological parameters as well as patients' outcome. Overall, peri- and intratumoral eosinophils were observed in 86 and 75% cancer specimens. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (R=0.69; P

To study the behavior of bovine disc cells and changes in disc matrix following in vitro compression tests; to compare the findings to investigations on human intervertebral discs (IVD) after burst fracture of the cervical spine. Healthy IVDs (n = 21) from three bovine tails were studied at 6 and 12 h post-mortem, with 16 IVDs subjected to impact loading and five as unloaded controls. IVDs (n = 8) from patients with burst fractures were compared to the bovine compression group. Specimens were studied macroscopically, histologically, and ultrastructurally for healthy cells, balloon cells, and disc cell death (DCD). Annulus ruptures were seen in both post-trauma groups, with radial ruptures being present histologically in all loaded bovine discs. Balloon cells were found in some human IVDs and were induced in vitro in bovine loaded discs within a distinct range of absorbed energy. There was a positive correlation between DCD and absorbed energy in all compartments of bovine discs. Both species showed similar patterns of DCD in the different compartments. This study was able to show similarities between both species in cell morphologies and matrix damage. The survival of the disc after substantial compression trauma thus seems to remain highly questionable. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1198–1207, 2014.

Study Design. Histological and ultrastructural evaluation of cell morphologies at the concave and convex side of apical intervertebral discs (IVD) of adolescent idiopathic scoliosis (AIS). Objective. To determine changes in cell morphology, viability, and cell death after asymmetric disc loading in AIS and to compare the findings with the tilt angles. Summary of Background Data. The reaction of cells to loading stimuli in the IVD seems to be specific. Although dynamic loads are more beneficial to the disc cells and maintain the matrix biosynthesis, static compressive loads suppress gene expression. Methods. Apical IVDs (Th8–Th9 to L1–L2) from 10 patients with AIS were studied histologically (including TUNEL [TdT-mediated dUTP-biotin nick end labeling] staining to identify disc cell death by apoptosis) and ultrastructurally for matrix evaluations and to quantify healthy, balloon, chondroptotic, apoptotic, and necrotic cells on the concave and convex sides. Patients' spines were classified according to the Lenke classification. Degeneration was assessed according to the Pfirrmann grading system. Two groups were established; group 1 (G1) with a tilt of 5° to 9° and group 2 (G2) with a tilt of 10° to 19°. Results. Balloon cells were found in significantly higher numbers at the concave side (G1—annulus fibrosus [AF]: mean 16%), with almost none found at the convex side. Mean numbers of healthy cells did not show differences comparing both sides. Significantly higher numbers of healthy cells were found with increasing tilt angle at the concave side. Necrosis (mean, 47%) increased toward the center of the disc but did not differ between the sides of the IVDs. The fibrils found in the outer AF on the convex side were 30% thinner. Conclusion. This study was able to show significant differences in cell morphologies in the AF on both sides and in correlation to the different tilt angles. The type and magnitude of load seem to influence disc cells. Further studies are required to provide more information on disc and cell changes in scoliosis.

In colorectal cancer, the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth, thus providing important prognostic information. The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage II disease.Tumors of 120 randomly selected patients with AJCC/UICC stage II disease were retrospectively reviewed for tumor growth pattern (expanding vs. infiltrating) and the extent of tumor budding, with high-grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin. Progression-free and cancer-specific survivals were determined by the Kaplan-Meier method. For multivariable analysis, Cox's proportional hazards regression models were performed.The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion, while high-grade budding was significantly associated with tumor grade and lymphovascular invasion. High-grade budding, but not the infiltrating growth pattern, was significantly associated with outcome in univariable analysis. Cox's proportional hazards regression models proved tumor budding to be an independent predictor of disease progression (hazard ratio 3.91, 95 % confidence interval 1.3-11.77; P = 0.02) and cancer-related death (hazard ratio 5.90, 95 % confidence interval 1.62-21.51; P = 0.007). The combination of infiltrating growth pattern and high-grade budding did not have a stronger prognostic significance than tumor budding alone.Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication, patient counseling, and design of clinical trials by using integrated multimodal therapy.

Background The optimal treatment strategy for burst fractures of the thoracolumbar junction is discussed controversially in the literature. Whilst 360° fusion has shown to result in better radiological outcome, recent studies have failed to show its superiority concerning clinical outcome. The morbidity associated with the additional anterior approach may account for these findings. The aim of this prospective observational study was therefore to compare two different techniques for 360° fusion in thoracolumbar burst fractures using either thoracoscopy or a transforaminal approach (transforaminal lumbar interbody fusion (TLIF)) to support the anterior column. Methods Posterior reduction and short-segmental fixation using angular stable pedicle screw systems were performed in all patients as a first step. Monocortical strut grafts were used for the anterior support in the TLIF group, whilst tricortical grafts or titanium vertebral body replacing implants of adjustable height were used in the combined posteroanterior group. At final follow-up, the radiological outcome was assessed by performing X-rays in a standing position. The clinical outcome was measured using five validated outcome scores. The morbidity associated with the approaches and the donor site was assessed as well. Results There were 21 patients in the TLIF group and 14 patients in the posteroanterior group included. The postoperative loss of correction was higher in the TLIF group (4.9° ± 8.3° versus 3.4° ± 6.4°, p > 0.05). There were no significant differences regarding the outcome scores between the two groups. There were no differences in terms of return to employment, leisure activities and back function either. More patients suffered from donor-site morbidity in the TLIF group, whilst the morbidity associated with the surgical approach was higher in the posteroanterior group. Conclusion The smaller donor-site morbidity in the posteroanterior group is counterbalanced by an additional morbidity associated with the anterior approach resulting in similar clinical outcome. Mastering both techniques will allow the spine surgeon to be more flexible in specific situations, for example, in patients with neurological deficits or severe concomitant thoracic trauma.

Langner C, Harbaum L, Pollheimer M J, Kornprat P, Lindtner R A, Schlemmer A, Vieth M & Rehak P (2012) Histopathology 60, 1060–1072 Mucinous differentiation in colorectal cancer – indicator of poor prognosis? Aims: To analyse the prognostic impact of mucinous differentiation in colorectal mucinous adenocarcinomas and adenocarcinomas with a mucinous component. Methods and results: A total of 381 tumours were reviewed for mucinous differentiation by two independent pathologists. Mismatch repair status was assessed by immunohistochemistry. Prognostic significance was assessed by univariate and multivariate analyses. Eighty-one (21%) tumours were Union Internationale Contre le Cancer (UICC) Stage I, 120 (31%) Stage II, 126 (33%) Stage III and 54 (14%) Stage IV. Mucinous adenocarcinomas accounted for 12% and adenocarcinomas with a mucinous component for 19% of tumours. Mucinous differentiation was associated significantly with mismatch repair protein deficiency. The presence of extracellular mucin, regardless of extent, did not affect patients’ outcome, while tumour grade, vascular and perineural invasion, tumour border configuration and budding were associated significantly with outcome. Cox analysis proved venous invasion to be an independent predictor of outcome in mucinous adenocarcinomas and both venous invasion and tumour budding as independent predictors of outcome in adenocarcinomas with any amount of mucin. Conclusions: Mucinous adenocarcinomas and/or adenocarcinomas with mucinous component do not differ from conventional adenocarcinomas with respect to prognosis and histological predictors of outcome. Hence, recording of mucinous differentiation may be used as an indicator of mismatch repair deficiency, but not for prognostic stratification.

BACKGROUND: Blood vessel invasion has been associated with poor outcome in colorectal cancer (CRC), whereas the prognostic impact of lymphatic invasion is less clear. The authors of this report evaluated venous and lymphatic invasion as potential prognostic indicators in patients with CRC focusing on lymph node-negative patients and compared routine and review pathology diagnoses. METHODS: In total, 381 tumors from randomly selected patients were retrospectively reviewed. The presence of vascular invasion was related to disease-free and cancer-specific survival using the Kaplan-Meier method. For multivariable analysis, Cox proportional hazards regression models were performed. RESULTS: Lymphatic invasion and venous invasion were observed in 126 patients (33%) and 87 patients (23%), respectively, and were associated significantly with tumor classification, lymph node status, American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) disease stage, tumor differentiation, pattern of invasion, and extent of tumor budding. The detection of vascular invasion was related to the number of examined tissue blocks. Venous and lymphatic invasion proved to be significant prognostic variables in univariable and multivariable analyses. Extramural vascular involvement was of particular significance. When the analysis was restricted to patients with (AJCC/UICC) stage II disease, venous invasion, but not lymphatic invasion, was identified as an independent prognostic variable. Review pathology diagnoses differed significantly from routine diagnoses with respect to prognostic impact. CONCLUSIONS: Venous and lymphatic invasion proved to be significant prognostic variables in patients with CRC. The detection of vascular invasion and, consequently, risk stratification of affected patients were related to the quality of pathology workup, ie, the number of examined tissue blocks. Observed differences between review and routine pathology diagnoses illustrated the need for high-quality pathology reporting and also for standardized quality control. Cancer 2012;. © 2011 American Cancer Society.

Vertical tumor growth, reflected by T classification, represents the most important prognostic variable in colorectal cancer. Our study aimed to investigate the impact of tumor size, particularly the maximum tumor diameter, on outcome of affected patients.A total of 381 colorectal cancer specimens were re-evaluated. Tumor size and location were extracted from the medical history and were known for 359 patients (94%). Receiver-operator characteristic analysis was applied to identify the optimal (maximum of sum of sensitivity and specificity) cut-off values with respect to prognostic impact.Median tumor size was 4.5 cm (range, 0.6-15). Tumor size exceeding 4.5 cm was observed in 159 patients (44%) and was associated with high T and N classification, UICC stage, and tumor grade. At median follow-up of 45 months (range, 0-180), 141 patients (40%) showed tumor progression. Although 4.5 cm was identified as the optimal cut-off value within the whole group of patients, receiver-operator characteristic analysis restricted to different parts of the large bowel determined 5 cm, 5.3 cm, 3.9 cm, and 3.4 cm as cut-off values with the strongest discriminatory capacity in colon, right-sided colon, left-sided colon, and rectum cancers, respectively. Applying these cut-off values, tumor size was significantly associated with progression-free and cancer-specific survival in univariate and multivariate analyses in colon, yet not in rectum cancers.Tumor size proved to be an independent prognostic parameter for patients with colorectal cancer. Optimal cut-off values vary among different parts of the large bowel. Whereas prognostic significance is strong within the colon, it appears to be of minor value within the rectum.

In the first 24 h post-intervertebral disc (IVD) trauma, up to 75 % cell death has been reported. In addition, burst fractures cause post-traumatic disc degeneration by elevated pro-apoptotic and pro-inflammatory gene transcription. Moreover, some patients have pre-trauma degenerative disc disease. The aim of the study was to assess histological changes and cell-death over a time period of up to 1 year caused by mechanical and structural factors. 116 anterior portions of IVDs of the cervical spine were studied histologically by light microscopy and ultrastructurally by transmission electron microscopy (TEM). The group was investigated with regard to three main parameters: fracture mechanism (compressive vs. tensile/shear loads), degeneration grade (low vs. high) and endplate fracture (with vs. without). Disc architecture (e.g. ruptures) was studied histologically. Cell morphology was examined ultrastructurally to quantify cell-death, healthy and balloon cells. According to ultrastructural observations, two time-groups (up to 6 days vs. later) were established. Statistical analyses were carried out within and between time-groups. Histological changes were obvious in the annulus fibrosus where ruptures with haematoma were replaced by granulation tissue. Significant differences in cell-death were seen in the first few days due to different loads. In contrast to the more degenerated segments, low degenerated ones revealed significantly less cell death with time post-trauma. Interestingly, no difference was found between groups after the sixth day. Cell-death (mean 44 % for all investigated groups) remained high after day 6 post-trauma. IVDs retrieved from low grade degenerated segments revealed a significant recovery, with less cell-death and a partially restored disc matrix, although cell-death remained high. Long-term clinical studies of stabilized segments arising from different fracture mechanisms are required.

This study aimed to assess the clinicopathological significance of tumour differentiation of metastatic lymph node tissue in patients with American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) stage III colorectal cancer. In a cohort of 145 patients, lymph node grades were G1 in 77 (53.1%), G2 in 41 (28.3%) and G3 in 27 (18.6%) cases, respectively. Despite differences in 77 (53.1%) cases, primary tumour and lymph node grade correlated significantly (Somer's D=0.639; p

Adipose-derived stromal cells (ASCs) are increasingly being used for orthopedic-based tissue engineering approaches due to their ability to readily undergo osteogenic differentiation. In the present study, we used in vitro and in vivo approaches to evaluate the use of ASCs as a treatment strategy for age-related osteoporosis. Molecular, histological and micro-computed tomography (micro-CT) based approaches confirmed that ASCs isolated from 18-week-old osteoporotic senescence-accelerated mice (SAMP6) were capable of undergoing osteogenesis when cultured in either silk fibroin (SF) scaffolds or scaffold-free microtissues (ASC-MT). A single intratibial injection of CM-Dil-labeled isogeneic ASCs or ASC-MT into SAMP6 recipients significantly improved trabecular bone quality after 6 weeks in comparison to untreated contralateral bones, as determined by micro-CT. Injected ASCs could be observed in paraffin wax bone sections at 24 h and 6 weeks post treatment and induced a significant increase in several molecular markers of bone turnover. Furthermore, a significant improvement in the osteogenic potential of osteoporotic patient-derived human bone marrow stromal cells (BMSCs) was observed when differentiated in conditioned culture media harvested from osteoporotic patient-derived human ASCs. These findings therefore support the use of ASCs as an autologous cell-based approach for the treatment of osteoporosis.

Summary: In the present study, we evaluated the potential for aminobisphosphonates to enhance the development of bone-forming osteoblasts from progenitor cells isolated from aged female osteoporotic patients. The aminobisphosphonates tested significantly enhanced osteoblast formation and thus lend further insights into their possible mode of action in the treatment of osteoporosis. Introduction: The primary aim of this study was to evaluate the influence of aminobisphosphonates on the osteogenesis of human bone marrow stromal cells (hBMSCs) and mineralization of differentiating bone-forming cells isolated from osteoporotic patients. Methods: The influence of aminobisphosphonate treatment on hBMSC osteogenesis was assessed by the quantitative measurement of alkaline phosphatase (ALP) activity, in addition to quantitative reverse transcription polymerase chain reaction and Western blot analysis of known osteogenic markers. Mineralized matrix formation by hBMSC-derived osteoblasts was visualized and quantified using Alizarin red staining. Results: hBMSC cultures treated with osteogenic medium supplemented with zoledronate demonstrated a significant increase in Alizarin red staining after 3weeks as compared to cells cultured in osteogenic medium alone. Similarly, cultures of differentiating hBMSCs isolated from patients receiving alendronate treatment also demonstrated an increased propensity for mineralization, even in the absence of further in vitro stimulation by zoledronate. The stimulatory effects of aminobisphosphonate treatment on hBMSC-derived osteoblast-mediated mineralization were independent of any alterations in ALP activity, although significant decreases in the expression levels of osteopontin (SPP1) were evident in hBMSCs following exposure to aminobisphosphonates. Further analysis including Western blotting and loss-of-function studies revealed osteopontin as having a negative influence on the mineralization of differentiating osteoporotic bone-forming cells. Conclusions: The results presented here demonstrate for the first time that aminobisphosphonate treatment of osteoporotic hBMSCs enhances their capacity for osteoblast formation and subsequent mineral deposition, thus supporting the concept of aminobisphosphonates as having an osteoanabolic effect in osteoporosis.

This study aimed to evaluate the prognostic significance of lymphatic invasion in colorectal cancers that have already spread to regional lymph nodes. 168 patients with node-positive tumours (colon, n=98; rectum, n=70) were retrospectively evaluated. Lymphatic invasion was assessed on HE stained slides and univariable and multivariable analyses were applied. Lymphatic invasion was detected in 95 (57%) cases and was significantly associated with tumour and node classification and tumour differentiation. Patients with tumours showing lymphatic invasion had decreased progression-free survival (p=0.025) and cancer-specific survival (p=0.082). Stratified by location, lymphatic invasion was significantly associated with decreased progression-free (p=0.010) and cancer-specific (p=0.023) survival in colon cancers, yet not in rectal cancers. Multivariable analysis proved T4 (HR 2.18, 95% CI 1.40 to 3.39; p0.001) and N2 (HR 1.68, 95% CI 1.07 to 2.66; p=0.03) as independent predictors of progression-free survival and T4 (HR 1.90, 95% CI 1.17 to 3.07; p=0.009), N2 (HR 2.27, 95% CI 1.38 to 3.73; p=0.001) and poor tumour differentiation (HR 2.18, 95% CI 1.39 to 3.43; p0.001) as independent predictors of cancer-specific survival, while for lymphatic invasion no influence on outcome was noted. In conclusion, only tumour and node classification, and tumour differentiation proved to be independent prognostic variables in node-positive colorectal cancer and merit special attention in clinical decision-making.

The prognostic significance of tumor necrosis in colorectal cancer is unclear. Our study aimed to analyze the prognostic value of tumor necrosis with respect to progression-free and cancer-specific survival and to relate findings to expression of proteins involved in the control of cancer cell death, such as p53 and bcl-2. A total of 381 colorectal cancer specimens were retrospectively reevaluated. The extent of tumor necrosis was semiquantitatively assessed and recorded as either absent, focal (≤10% of the tumor area), moderate (10%-30%), or extensive (≥30%). Expression of p53 and bcl-2 was assessed immunohistochemically and recorded as either positive (using a cutoff value of 10%) or negative. In addition, mismatch repair protein status was assessed by immunohistochemistry using antibodies directed against hMLH1, hMSH2, and hMSH6. Tumor necrosis was observed in 365 (96%) cases, with 180 (47%) tumors showing focal necrosis, 119 (31%) moderate necrosis, and 66 (17%) extensive necrosis, respectively. Extent of necrosis was significantly associated with high T classification (P < .001), high N classification (P = .005), high International Union Against Cancer stage (P < .001), poor tumor differentiation (P < .001), large tumor size (P < .001), and blood vessel invasion (P = .01). No association of tumor necrosis with expression of p53, bcl-2, and mismatch repair protein status was observed. Tumor necrosis proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. In conclusion, tumor necrosis showed significant impact on prognosis of colorectal cancer patients. Its presence is readily assessable in hematoxylin and eosin-stained sections and should therefore routinely be commented upon in the pathology report.

Tumour stage is the strongest prognostic parameter in colorectal cancer. The study aimed to evaluate the prognostic impact of pT2, pT3, and pT4 sub-classification. Three hundred eighty-one surgical colorectal cancer specimens were retrospectively re-evaluated. pT2 tumours were sub-classified according to infiltration of the inner circumferential (pT2a) or outer longitudinal (pT2b) layer of the muscularis propria. pT3 tumours were sub-classified by measuring the maximal tumour invasion beyond the outer border of the muscularis propria (pT3a ≤ 1 mm, pT3b > 1–5 mm, pT3c > 5–15 mm, and pT3d > 15 mm). pT4 tumours were sub-classified according to invasion of other organs or structures (pT4a) or perforation of the visceral peritoneum (pT4b). Data were correlated with other pathological parameters and patient outcome. Seventy pT2 tumours were re-classified as 37 pT2a and 33 pT2b tumours. There was no significant association with tumour grade, angioinvasion, or lymph node involvement and no significant impact on prognosis. Two hundred eighteen pT3 tumours were re-classified as 49 pT3a, 83 pT3b, 53 pT3c, and 33 pT3d tumours. pT3 sub-classification was significantly associated with tumour grade, angioinvasion, and lymph node involvement and proved to be an independent prognostic variable with respect to progression-free and cancer-specific survival. A cut-off level of 5 mm is recommended. Sixty-five pT4 tumours were re-classified as 15 pT4a and 50 pT4b tumours. There was no significant association with tumour grade, angioinvasion, or lymph node involvement and no significant impact on prognosis. pT3 sub-classification was significantly associated with patient outcome. In contrast, pT2 and pT4 sub-classification did not show clinical significance.

Purpose The study aimed to analyze clinicopathological factors that determine the extent of lymph node retrieval and to evaluate its prognostic impact in patients with colorectal cancer (CRC). Methods The number of retrieved lymph nodes was analyzed in 381 CRC specimens. Lymph node count was related to different clinicopathological variables by binary logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method and Cox regression models. Results The median number of retrieved lymph nodes was 20 (mean 21 ± 10, range 1–65) in right-sided, 13 (16 ± 10, 1–66) in left-sided, and 15 (18 ± 11, 3–64) in rectal tumors. The number of retrieved lymph nodes was independently associated with T-classification (p

Objectives Bone bridge formation occurs after physeal lesions and can lead to growth arrest if not reversed. Previous investigations on the underlying mechanisms of this formation used histological methods. Therefore, this study aimed to apply a minimally invasive method using dynamic contrast-enhanced MRI (DCE-MRI). Materials and methods Changes in functional parameters related to the microvessel system were assessed in a longitudinal study of a cohort of an animal model applying a reference region model. The development of morphology of the injured physis was investigated with 3D high-resolution MRI. To acquire complementary information for MRI-related findings qRT-PCR and immunohistochemical data were acquired for a second cohort of the animal model. Results The evaluation of the pharmacokinetic parameters showed a first rise of the transfer coefficient 7 days post-lesion and a maximum 42 days after operation. The analysis of the complementary data showed a connection of the first rise to microvessel proliferation while the maximum value was linked to bone remodeling. Conclusion The pharmacokinetic analysis of DCE-MRI provides information on a proliferation of microvessels during the healing process as a sign for bone bridge formation. Thereby, DCE-MRI could identify details, which up to now required analyses of highly invasive methods.