The Significance of Removing Ruptured Intervertebral Discs for Interbody Fusion in Treating Thoracic or Lumbar Type B and C Spinal Injuries through a One-Stage Posterior Approach

Objectives

To identify the negative effect on treatment results of reserving damaged intervertebral discs when treating type B and type C spinal fracture-dislocations through a one-stage posterior approach.

Methods

This is a retrospective review of 53 consecutive patients who were treated in our spine surgery center from January 2005 to May 2012 due to severe thoracolumbar spinal fracture-dislocation. The patients in Group A (24 patients) underwent long-segment instrumentation laminectomy with pedicle screw-rod fixators for neural decompression. In Group B (29 patients), the patients underwent long-segment instrumentation laminectomy with pedicle screw-rod fixators for neural decompression evacuating of the ruptured disc and inserting of a bone graft into the evacuated disc space for interbody fusion. The mean time between injury and operation was 4.1 days (range 2–15 days). The clinical, radiologic and complication outcomes were analyzed retrospectively.

Results

Periodic follow-ups were carried out until an affirmative union or treatment failure took place. A progressive kyphosis angle larger than 10°, loss of disc height, pseudoarthrosis, recurrence of dislocation or subluxation, or instrument failure before fusion were considered treatment failures. Treatment failures were detected in 13 cases in Group A (failure rate was 54.2%). In Group B, there were 28 cases in which definitive bone fusion was demonstrated on CT scans, and CT scans of the other cases demonstrated undefined pseudoarthrosis without hardware failure. There were statistically significant differences between the two groups (p<0.001 chi-square test). The neurologic recoveries, assessed by the ASIA scoring system, were not satisfactory for the neural deficit patients in either group, indicating there was no significant difference with regard to neurologic recovery between the two groups (p>0.05 Fisher''s exact test).

Conclusion

Intervertebral disc damage is a common characteristic in type B and C spinal fracture-dislocation injuries. The damaged intervertebral disc should be removed and substituted with a bone graft because reserving the damaged disc in situ increases the risk of treatment failure.     

Trans-Endplate Pedicle Pillar System in Unstable Spinal Burst Fractures: Design,Technique, and Mechanical Evaluation

Background

Short-segment pedicle screw instrumentation (SSPI) is used for unstable burst fractures to correct deformity and stabilize the spine for fusion. However, pedicle screw loosening, pullout, or breakage often occurs due to the large moment applied during spine motion, leading to poor outcomes. The purpose of this study was to test the ability of a newly designed device, the Trans-Endplate Pedicle Pillar System (TEPPS), to enhance SSPI rigidity and decrease the screw bending moment with a simple posterior approach.

Methods

Six human cadaveric spines (T11-L3) were harvested. A burst fracture was created at L1, and the SSPI (Moss Miami System) was used for SSPI fixation. Strain gauge sensors were mounted on upper pedicle screws to measure screw load bearing. Segmental motion (T12-L2) was measured under pure moment of 7.5 Nm. The spine was tested sequentially under 4 conditions: intact; first SSPI alone (SSPI-1); SSPI+TEPPS; and second SSPI alone (SSPI-2).

Results

SSPI+TEPPS increased fixation rigidity by 41% in flexion/extension, 28% in lateral bending, and 37% in axial rotation compared with SSPI-1 (P<0.001), and it performed even better compared to SSPI-2 (P<0.001 for all). Importantly, the bending moment on the pedicle screws for SSPI+TEPPS was significantly decreased 63% during spine flexion and 47% in lateral bending (p<0.001).

Conclusion

TEPPS provided strong anterior support, enhanced SSPI fixation rigidity, and dramatically decreased the load on the pedicle screws. Its biomechanical benefits could potentially improve fusion rates and decrease SSPI instrumentation failure.     

A Systematic Review and Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Transforaminal Lumbar Interbody Fusion

Background

Transforaminal lumbar interbody fusion (TLIF) has become one of the most widely used procedures for lumbar spinal disorders. However, it is still unclear whether TLIF with unilateral pedicle screw (PS) fixation is as effective as that with bilateral PS fixation. We performed a meta-analysis of the literatures and aimed to gain a better understanding of whether TLIF with unilateral PS fixation was safe and effective for lumbar diseases.

Methodology/Principal Findings

We systematically searched Ovid, Springer, and Medline databases for relevant randomized controlled trials (RCTs) that compared the clinical and radiological outcomes of unilateral versus bilateral PS fixation in TLIF. Risk of bias in included studies was assessed using the Cochrane Risk of Bias tool. We generated pooled risk ratios or weighted mean differences across studies. According to our predefined inclusion criteria, seven RCTs with a total of 441 patients were included in this study. Baseline characteristics were similar between the unilateral and bilateral groups. Our meta-analysis showed that no significant difference was detected between the two groups in terms of postoperative clinical function, fusion status, reoperation rate, complication rate, and hospital stay (p>0.05). Pooled estimates revealed that the unilateral group was associated with significantly reduced implant cost, operative time and blood loss (p<0.05).

Conclusions/Significances

Our meta-analysis suggested TLIF with unilateral PS fixation was as safe and effective as that with bilateral PS fixation for lumbar diseases in selected patients. Despite these findings, our meta-analysis was based on studies with small sample size and different study characteristics that might lead to the inconsistent results such as various functional outcomes among the included studies. Therefore, high-quality randomized controlled trials with larger sample size are also needed to further clarify these issues and to provide the long-term outcomes.     

A Robot-Assisted Surgical System Using a Force-Image Control Method for Pedicle Screw Insertion

Objective

To introduce a robot-assisted surgical system for spinal posterior fixation that can automatically recognize the drilling state and stop potential cortical penetration with force and image information and to further evaluate the accuracy and safety of the robot for sheep vertebra pedicle screw placement.

Methods

The Robotic Spinal Surgery System (RSSS) was composed of an optical tracking system, a navigation and planning system, and a surgical robot equipped with a 6-DOF force/torque sensor. The robot used the image message and force signals to sense the different operation states and to prevent potential cortical penetration in the pedicle screw insertion operation. To evaluate the accuracy and safety of the RSSS, 32 screw insertions were conducted. Furthermore, six trajectories were deliberately planned incorrectly to explore whether the robot could recognize the different drilling states and immediately prevent cortical penetration.

Results

All 32 pedicle screws were placed in the pedicle without any broken pedicle walls. Compared with the preoperative planning, the average deviations of the entry points in the axial and sagittal views were 0.50±0.33 and 0.65±0.40 mm, and the average deviations of the angles in the axial and sagittal views were 1.9±0.82° and 1.48±1.2°. The robot successfully recognized the different drilling states and prevented potential cortical penetration. In the deliberately incorrectly planned trajectory experiments, the robot successfully prevented the cortical penetration.

Conclusion

These results verified the RSSS’s accuracy and safety, which supported its potential use for the spinal surgery.     

Phenotyping community-acquired pneumonia according to the presence of acute respiratory failure and severe sepsis

Background

Acute respiratory failure (ARF) and severe sepsis (SS) are possible complications in patients with community-acquired pneumonia (CAP). The aim of the study was to evaluate prevalence, characteristics, risk factors and impact on mortality of hospitalized patients with CAP according to the presence of ARF and SS on admission.

Methods

This was a multicenter, observational, prospective study of consecutive CAP patients admitted to three hospitals in Italy, Spain, and Scotland between 2008 and 2010. Three groups of patients were identified: those with neither ARF nor SS (Group A), those with only ARF (Group B) and those with both ARF and SS (Group C) on admission.

Results

Among the 2,145 patients enrolled, 45% belonged to Group A, 36% to Group B and 20% to Group C. Patients in Group C were more severe than patients in Group B. Isolated ARF was correlated with age (p < 0.001), COPD (p < 0.001) and multilobar infiltrates (p < 0.001). The contemporary occurrence of ARF and SS was associated with age (p = 0.002), residency in nursing home (p = 0.007), COPD (p < 0.001), multilobar involvement (p < 0.001) and renal disease (p < 0.001). 4.2% of patients in Group A died, 9.3% in Group B and 26% in Group C, p < 0.001. After adjustment, the presence of only ARF had an OR for in-hospital mortality of 1.85 (p = 0.011) and the presence of both ARF and SS had an OR of 6.32 (p < 0.001).

Conclusions

The identification of ARF and SS on hospital admission can help physicians in classifying CAP patients into three different clinical phenotypes.     

Preoperative Measurement of Breast Cancer Overestimates Tumor Size Compared to Pathological Measurement

Background

Tumor size is one of the most important factors in making clinical and pathological assessment of breast cancer. In the present study, we aimed to determine whether the preoperative measurement of tumor size, by imaging modalities, deviate from the postoperative pathological measurement in breast cancer.

Patients and Methods

1296 patients diagnosed with invasive ductal breast carcinoma (IDC) during 2007 and 2009 were involved. Pre- and postoperative measurements of tumor size were compared using paired t-test and Chi-square test.

Results

The mean maximum diameters of tumors by imaging modalities and pathology were 27.9 mm and 22.4 mm, respectively. There was a statistically significant difference of 5.5 mm (95% CI: 4.7–6.2, p<0.001) between them. The discordance between pre- and post-surgical measurements of tumor size had significant effect on choosing surgery type, causing less application of breast conserving therapy (p<0.0001).

Conclusion

Compared to pathological size, preoperative measurement by imaging modalities tends to overestimate tumor size. These differences could have implications in the treatment of patients with breast cancer.     

Can Contemporary Patients with Biopsy Gleason Score 3+4 Be Eligible for Active Surveillance?

Introduction

We analyzed whether expansion of existing active surveillance (AS) protocols to include men with biopsy Gleason score (GS) 3+4 prostate cancer (PCa) would significantly alter pathologic and biochemical outcomes of potential candidates of AS.

Methods

Among patients who underwent radical prostatectomy at our center between 2006 and 2013, we identified 577 patients (group A) who preoperatively fulfilled at least one of 6 different AS criteria. Also, we identified 217 patients (group B) with biopsy GS 3+4 but fulfilled non-GS criteria from at least one of 6 AS criteria. Designating group C as expanded group incorporating all patients in group A and B, we compared risk of unfavorable disease (pathologic GS ≥4+3 and/or pathologic T stage ≥pT3a) and biochemical recurrence (BCR)-free survival between groups.

Results

Rates of unfavorable disease were not significantly different between patients of group A and C who met AS criteria from 5 institutions (all p>0.05), not including University of Toronto (p<0.001). Also BCR-free survivals were not significantly different between patients in group A and C meeting each of 6 AS criteria (all p>0.05). Among group B, PSAD>0.15 ng/mL/cm³ (p = 0.011) and tumor length of biopsy GS 3+4 core>4 mm (p = 0.007) were significant predictors of unfavorable disease. When these two criteria were newly applied in defining group B, rates of unfavorable disease in group A and B was 15.6% and 14.7%, respectively (p = 0.886).

Conclusion

Overall rate of pathologically aggressive PCa harbored by potential candidates for AS may not be increased significantly with expansion of criteria to biopsy GS 3+4 under most contemporary AS protocols. PSAD and tumor length of biopsy GS 3+4 core may be useful predictors of more aggressive disease among potential candidates for AS with biopsy GS 3+4.     

Biomechanical Analysis of a Newly Developed Shape Memory Alloy Hook in a Transforaminal Lumbar Interbody Fusion (TLIF) In Vitro Model

Objective

The objective of this biomechanical study was to evaluate the stability provided by a newly developed shape memory alloy hook (SMAH) in a cadaveric transforaminal lumbar interbody fusion (TLIF) model.

Methods

Six human cadaveric spines (L1-S2) were tested in an in vitro flexibility experiment by applying pure moments of ±8 Nm in flexion/extension, left/right lateral bending, and left/right axial rotation. After intact testing, a TLIF was performed at L4-5. Each specimen was tested for the following constructs: unilateral SMAH (USMAH); bilateral SMAH (BSMAH); unilateral pedicle screws and rods (UPS); and bilateral pedicle screws and rods (BPS). The L3–L4, L4–L5, and L5-S1 range of motion (ROM) were recorded by a Motion Analysis System.

Results

Compared to the other constructs, the BPS provided the most stability. The UPS significantly reduced the ROM in extension/flexion and lateral bending; the BSMAH significantly reduced the ROM in extension/flexion, lateral bending, and axial rotation; and the USMAH significantly reduced the ROM in flexion and left lateral bending compared with the intact spine (p<0.05). The USMAH slightly reduced the ROM in extension, right lateral bending and axial rotation (p>0.05). Stability provided by the USMAH compared with the UPS was not significantly different. ROMs of adjacent segments increased in all fixed constructs (p>0.05).

Conclusions

Bilateral SMAH fixation can achieve immediate stability after L4–5 TLIF in vitro. Further studies are required to determine whether the SMAH can achieve fusion in vivo and alleviate adjacent segment degeneration.     

Therapeutic Efficacy of Combining PEGylated Liposomal Doxorubicin and Radiofrequency (RF) Ablation: Comparison between Slow-Drug-Releasing,Non-Thermosensitive and Fast-Drug-Releasing,Thermosensitive Nano-Liposomes

Aims

To determine how the accumulation of drug in mice bearing an extra-hepatic tumor and its therapeutic efficacy are affected by the type of PEGylated liposomal doxorubicin used, treatment modality, and rate of drug release from the liposomes, when combined with radiofrequency (RF) ablation.

Materials and Methods

Two nano-drugs, both long-circulating PEGylated doxorubicin liposomes, were formulated: (1) PEGylated doxorubicin in thermosensitive liposomes (PLDTS), having a burst-type fast drug release above the liposomes’ solid ordered to liquid disordered phase transition (at 42°C), and (2) non-thermosensitive PEGylated doxorubicin liposomes (PLDs), having a slow and continuous drug release. Both were administered intravenously at 8 mg/kg doxorubicin dose to tumor-bearing mice. Animals were divided into 6 groups: no treatment, PLD, RF, RF+PLD, PLDTS, and PLDTS+RF, for intra-tumor doxorubicin deposition at 1, 24, and 72 h post-injection (in total 41, mice), and 31 mice were used for randomized survival studies.

Results

Non-thermosensitive PLD combined with RF had the least tumor growth and the best end-point survival, better than PLDTS+RF (p<0.005) or all individual therapies (p<0.001). Although at 1 h post-treatment the greatest amount of intra-tumoral doxorubicin was seen following PLDTS+RF (p<0.05), by 24 and 72 h the greatest doxorubicin amount was seen for PLD+RF (p<0.05); in this group the tumor also has the longest exposure to doxorubicin.

Conclusion

Optimizing therapeutic efficacy of PLD requires a better understanding of the relationship between the effect of RF on tumor microenvironment and liposome drug release profile. If drug release is too fast, the benefit of changing the microenvironment by RF on tumor drug localization and therapeutic efficacy may be much smaller than for PLDs having slow and temperature-independent drug release. Thus the much longer circulation time of doxorubicin from PLD than from PLDTS may be beneficial in many therapeutic instances, especially in extra-hepatic tumors.     

Trends in Condom Use and Risk Behaviours after Sexual Exposure to HIV: A Seven-Year Observational Study

Objective

We aimed to determine the trends in numbers and percentages of sexually exposed persons to HIV (SE) consulting an ED for post-exposure prophylaxis (PEP), as well as predictors of condom use.

Study Design

We conducted a prospective-observational study.

Methods

We included all SE attendances in our Emergency Department (ED) during a seven-year study-period (2006–2012). Trends were analyzed using time-series analysis. Logistic Regression was used to define indicators of condom use.

Results

We enrolled 1851 SE: 45.7% reported intercourse without condom-use and 12.2% with an HIV-infected partner. Significant (p<0.01) rising trends were observed in the overall number of SE visits (+75%), notably among men having sex with men (MSM) (+126%). There were rising trends in the number and percentage of those reporting intercourse without condom-use in the entire population +91% (p<0.001) and +1% (p>0.05), in MSM +228% (p<0.001) and +49% (p<0.001), in Heterosexuals +68% (p<0.001) and +10% (p = 0.08). Among MSM, significant rising trends were found in those reporting high-risk behaviours: anal receptive (+450% and +76%) and anal insertive (+l33% and +70%) intercourses. In a multivariate logistic regression analysis, heterosexuals, vaginal intercourse, visit during the night-shift and short time delay between SE and ED visit, were significantly associated with condom-use.

Conclusion

We report an increasing trend in the number of SE, mainly among MSM, and rising trends in high-risk behaviours and unprotected sexual intercourses among MSM. Our results indicate that SE should be considered as a high-risk population for HIV and sexually transmitted diseases.     

A Combined Supplementation of Omega-3 Fatty Acids and Micronutrients (Folic Acid,Vitamin B12) Reduces Oxidative Stress Markers in a Rat Model of Pregnancy Induced Hypertension

Objectives

Our earlier studies have highlighted that an altered one carbon metabolism (vitamin B₁₂, folic acid, and docosahexaenoic acid) is associated with preeclampsia. Preeclampsia is also known to be associated with oxidative stress and inflammation. The current study examines whether maternal folic acid, vitamin B₁₂ and omega-3 fatty acid supplementation given either individually or in combination can ameliorate the oxidative stress markers in a rat model of pregnancy induced hypertension (PIH).

Materials and Methods

Pregnant Wistar rats were assigned to control and five treatment groups: PIH; PIH + vitamin B₁₂; PIH + folic acid; PIH + Omega-3 fatty acids and PIH + combined micronutrient supplementation (vitamin B₁₂ + folic acid + omega-3 fatty acids). L-Nitroarginine methylester (L-NAME; 50 mg/kg body weight/day) was used to induce hypertension during pregnancy. Blood Pressure (BP) was recorded during pregnancy and dams were dissected at d20 of gestation.

Results

Animals from the PIH group demonstrated higher (p<0.01 for both) systolic and diastolic BP; lower (p<0.01) pup weight; higher dam plasma homocysteine (p<0.05) and dam and offspring malondialdehyde (MDA) (p<0.01), lower (p<0.05) placental and offspring liver DHA and higher (p<0.01) tumor necrosis factor–alpha (TNF–ά) levels as compared to control. Individual micronutrient supplementation did not offer much benefit. In contrast, combined supplementation lowered systolic BP, homocysteine, MDA and placental TNF-ά levels in dams and liver MDA and protein carbonyl in the offspring as compared to PIH group.

Conclusion

Key constituents of one carbon cycle (folic acid, vitamin B₁₂ and DHA) may play a role in reducing oxidative stress and inflammation in preeclampsia.     

CT Morphometric Analysis to Determine the Anatomical Basis for the Use of Transpedicular Screws during Reconstruction and Fixations of Anterior Cervical Vertebrae

Background

Accurate placement of pedicle screw during Anterior Transpedicular Screw fixation (ATPS) in cervical spine depends on accurate anatomical knowledge of the vertebrae. However, little is known of the morphometric characteristics of cervical vertebrae in Chinese population.

Methods

Three-dimensional reconstructions of CT images were performed for 80 cases. The anatomic data and screw fixation parameters for ATPS fixation were measured using the Mimics software.

Findings

The overall mean OPW, OPH and PAL ranged from 5.81 to 7.49 mm, 7.77 to 8.69 mm, and 33.40 to 31.13 mm separately, and SPA was 93.54 to 109.36 degrees from C3 to C6, 104.99 degrees at C7, whereas, 49.00 to 32.26 degrees from C4 to C7, 46.79 degrees at C3 (TPA). Dl/rSIP had an increasing trend away from upper endplate with mean value from 1.87 to 5.83 mm. Dl/rTIP was located at the lateral portion of the anterior cortex of vertebrae for C3 to C5 and ipsilateral for C6 to C7 with mean value from −2.70 to −3.00 mm, and 0.17 to 3.18 mm. The entrance points for pedicular screw insertion for C3 to C5 and C6 to C7 were recommended −2∼−3 mm and 0–4 mm from the median sagittal plane, respectively, 1–4 mm and 5–6 mm from the upper endplate, with TPA being 46.79–49.00 degrees and 40.89–32.26 degrees, respectively, and SPA being 93.54–106.69 degrees and 109.36–104.99 degrees, respectively. The pedicle screw insertion diameter was recommended 3.5 mm (C3 and C4), 4.0 mm (C5 to C7), and the pedicle axial length was 21–24 mm for C3 to C7 for both genders. However, the ATPS insertion in C3 should be individualized given its relatively small anatomical dimensions.

Conclusions

The data provided a morphometric basis for the ATPS fixation technique in lower cervical fixation. It will help in preoperative planning and execution of this surgery.     

Dynamic Biomechanical Examination of the Lumbar Spine with Implanted Total Spinal Segment Replacement (TSSR) Utilizing a Pendulum Testing System

Background

Biomechanical investigations of spinal motion preserving implants help in the understanding of their in vivo behavior. In this study, we hypothesized that the lumbar spine with implanted total spinal segment replacement (TSSR) would exhibit decreased dynamic stiffness and more rapid energy absorption compared to native functional spinal units under simulated physiologic motion when tested with the pendulum system.

Methods

Five unembalmed, frozen human lumbar functional spinal units were tested on the pendulum system with axial compressive loads of 181 N, 282 N, 385 N, and 488 N before and after Flexuspine total spinal segment replacement implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5°; resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode.

Results

The total spinal segment replacement reached equilibrium with significantly fewer cycles to equilibrium compared to the intact functional spinal unit at all loads in flexion (p<0.011), and at loads of 385 N and 488 N in lateral bending (p<0.020). Mean bending stiffness in flexion, extension, and lateral bending increased with increasing load for both the intact functional spinal unit and total spinal segment replacement constructs (p<0.001), with no significant differences in stiffness between the intact functional spinal unit and total spinal segment replacement in any of the test modes (p>0.18).

Conclusions

Lumbar functional spinal units with implanted total spinal segment replacement were found to have similar dynamic bending stiffness, but absorbed energy at a more rapid rate than intact functional spinal units during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices is not fully known, these results provide further insight into the biomechanical behavior of this device under approximated physiologic loading conditions.     

A Meta-Analysis of Unilateral versus Bilateral Pedicle Screw Fixation in Minimally Invasive Lumbar Interbody Fusion

Study Design

Meta-analysis.

Background

Bilateral pedicle screw fixation (PS) after lumbar interbody fusion is a widely accepted method of managing various spinal diseases. Recently, unilateral PS fixation has been reported as effective as bilateral PS fixation. This meta-analysis aimed to comparatively assess the efficacy and safety of unilateral PS fixation and bilateral PS fixation in the minimally invasive (MIS) lumbar interbody fusion for one-level degenerative lumbar spine disease.

Methods

MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched through March 30, 2014. Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on unilateral versus bilateral PS fixation in MIS lumbar interbody fusion that met the inclusion criteria and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.2.

Results

Six studies (5 RCTs and 1 CCT) involving 298 patients were selected. There were no significant differences between unilateral and bilateral PS fixation procedures in fusion rate, complications, visual analogue score (VAS) for leg pain, VAS for back pain, Oswestry disability index (ODI). Both fixation procedures had similar length of hospital stay (MD = 0.38, 95% CI = −0.83 to 1.58; P = 0.54). In contrast, bilateral PS fixation was associated with significantly more intra-operative blood loss (P = 0.002) and significantly longer operation time (P = 0.02) as compared with unilateral PS fixation.

Conclusions

Unilateral PS fixation appears as effective and safe as bilateral PS fixation in MIS lumbar interbody fusion but requires less operative time and causes less blood loss, thus offering a simple alternative approach for one-level lumbar degenerative disease.     

Acylation Stimulating Protein,Complement C3 and Lipid Metabolism in Ketosis-Prone Diabetic Subjects

Background

Ketosis-prone diabetes (KPDM) is new-onset diabetic ketoacidosis without precipitating factors in non-type 1 diabetic patients; after management, some are withdrawn from exogenous insulin, although determining factors remain unclear.

Methods

Twenty KPDM patients and twelve type 1 diabetic patients (T1DM), evaluated at baseline, 12 and 24 months with/without insulin maintenance underwent a standardized mixed-meal tolerance test (MMTT) for 2 h.

Results

At baseline, triglyceride and C3 were higher during MMTT in KPDM vs. T1DM (p<0.0001) with no differences in non-esterified fatty acids (NEFA) while Acylation Stimulating Protein (ASP) tended to be higher. Within 12 months, 11 KPDM were withdrawn from insulin treatment (KPDM-ins), while 9 were maintained (KPDM+ins). NEFA was lower in KPDM-ins vs. KPDM+ins at baseline (p = 0.0006), 12 months (p<0.0001) and 24 months (p<0.0001) during MMTT. NEFA in KPDM-ins decreased over 30–120 minutes (p<0.05), but not in KPDM+ins. Overall, C3 was higher in KPDM-ins vs KPDM+ins at 12 months (p = 0.0081) and 24 months (p = 0.0019), while ASP was lower at baseline (p = 0.0024) and 12 months (p = 0.0281), with a decrease in ASP/C3 ratio.

Conclusions

Notwithstanding greater adiposity in KPDM-ins, greater NEFA decreases and lower ASP levels during MMTT suggest better insulin and ASP sensitivity in these patients.     

Bilateral C1–C2 Transarticular Screw and C1 Laminar Hook Fixation and Bone Graft Fusion for Reducible Atlantoaxial Dislocation: A Seven-Year Analysis of Outcome

Background

Bilateral C1-2 transarticular screw and C1 laminar hook fixation was developed on the basis of transarticular screws fixation. The modified technique has showed a better biomechanical stability than established techniques in previous study. However, long-term (minimum follow-up 7 years) outcomes of patients with reducible atlantoaxial dislocation who underwent this modified fixation technique have not still been reported.

Methods

A retrospective study was conducted to evaluate the outcome of 36 patients who underwent this modified technique. Myelopathy was assessed using the Ranawat myelopathy score and Myelopathy Disability Index. Pain scores were assessed using Visual Analogue Scale. Radiological imaging was assessed and the following data were extracted: the atlantodental intervals, the space available for cord, presence of spinal cord signal change on T2 weighted image, C1–C2 angle, C2–C7 angle and fusion rates.

Findings

All patients achieved a minimum seven-year follow up. 95% patients with neck and suboccipital pain improved after surgery; in their Visual Analogue pain scores, there was a greater than 50% improvement in their VAS scores with a drop of 5 points on the VAS (P<0.05). 92% of patients improved in the Ranawat myelopathy grade; the Myelopathy Disability Index assessment showed a preoperative mean score of 35.62 with postoperative mean 12.75(P<0.05). There was not any significant atlantoaxial instability at each follow-up time. The space available for cord increased in all patients. Postoperative sagittal kyphosis of the subaxial spine was not observed. After six months after surgery, bone grafts of all patients were fused. No complications related to surgery were found in the period of follow-up.

Conclusions

The long-term outcomes of this case series demonstrate that under the condition of thorough preoperative preparations, bilateral C1–C2 transarticular screw and C1 laminar hook fixation and bone graft fusion is a reliable posterior atlantoaxial fusion technique for reducible atlantoaxial dislocation.     

Concomitant Tumor Expression of EGFR and TATI/SPINK1 Associates with Better Prognosis in Colorectal Cancer

Background

Epidermal growth factor receptor (EGFR) activation plays a role in colorectal cancer (CRC) carcinogenesis, and anti-EGFR drugs are used in treatment of advanced CRC. One of the EGFR ligands is tumor-associated trypsinogen inhibitor TATI, also called serine protease inhibitor Kazal type1 (SPINK 1), which we recently showed to be an independent prognostic marker in CRC.

Methods

We studied the prognostic value of immunohistochemical expression of EGFR and concomitant expression of EGFR and TATI/SPINK1 in a series of 619 colorectal cancer patients.

Results

Of the samples, 92% were positive for EGFR. EGFR+/TATI+ was seen in 62.8%, EGFR+/TATI− in 29.5%, EGFR−/TATI+ in 4.9%, and EGFR−/TATI− in 2.7% of patients. EGFR expression correlated with WHO grade (p = 0.040). In univariate analysis, EGFR expression correlated with favourable survival (p = 0.006). EGFR+/TATI+ patients showed better survival than did those with other combinations (p<0.001). In multivariate analysis, EGFR+/TATI+ was an independent prognostic factor of favourable prognosis (p<0.001).

Conclusion

Concomitant positivity of EGFR and TATI/SPINK1 predicts favourable prognosis in CRC.     

Low Frequency Magnetic Fields Enhance Antitumor Immune Response against Mouse H22 Hepatocellular Carcinoma

Objective

Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear.

Methods

In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured.

Results

MF treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced production of cytokines including interleukin-6 (IL-6), granulocyte colony- stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9–10, p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4⁺ T and CD8⁺ T lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg cells (n = 9–10, p<0.05 or 0.01) in the mice model.

Conclusion

The inhibitory effect of MF on tumor growth was related to the improvement of immune function in the tumor-bearing mice.     

Regulatory T Lymphocytes Are Associated with Less Aggressive Histologic Features in Microsatellite-Unstable Colorectal Cancers

Background

Colorectal cancers (CRCs) with microsatellite instability (MSI) are associated with a good prognosis and a high density of tumor-infiltrating lymphocytes (TILs). We have undertaken to determine the link between TIL densities and MSI CRC histologic features.

Patients and Methods

Using tissue microarrays, T-cell sub-population infiltration, including T cells (CD3), cytotoxic T cells (CD8) and regulatory T cells (FoxP3) were studied in 86 MSI CRCs. We separately analyzed TILs of the stromal and epithelial compartments in the tumor center, the tumoral invasion margin and associated normal tissue.

Results

For FoxP3+ TIL density in the tumor center stromal compartment, we found a strong negative correlation with T4 stage (p = 0.01), node invasion (p<0.001) and VELIPI (vascular emboli, lymphatic invasion and perinervous invasion) criteria (p = 0.002).

Conclusion

The strong correlation between regulatory T cell density and the absence of VELIPI criteria suggests that this sub-group of T cells is preferentially associated with less invasive tumors.     

CD166/ALCAM Expression Is Characteristic of Tumorigenicity and Invasive and Migratory Activities of Pancreatic Cancer Cells

Background

CD166, also known as activated leukocyte cell adhesion molecule (ALCAM), is expressed by various cells in several tissues including cancer. However, the role of CD166 in malignant tumors is controversial, especially in pancreatic cancer. This study aimed to clarify the role and significance of CD166 expression in pancreatic cancer.

Methods

We performed immunohistochemistry and flow cytometry to analyze the expression of CD166 in surgical pancreatic tissues and pancreatic cancer cell lines. The differences between isolated CD166+ and CD166- pancreatic cancer cells were analyzed by invasion and migration assays, and in mouse xenograft models. We also performed quantitative RT-PCR and microarray analyses to evaluate the expression levels of CD166 and related genes in cultured cells.

Results

Immunohistochemistry revealed high expression of CD166 in pancreatic cancer tissues (12.2%; 12/98) compared with that in normal pancreas controls (0%; 0/17) (p = 0.0435). Flow cytometry indicated that CD166 was expressed in 33.8–70.2% of cells in surgical pancreatic tissues and 0–99.5% of pancreatic cancer cell lines. Invasion and migration assays demonstrated that CD166- pancreatic cancer cells showed stronger invasive and migratory activities than those of CD166+ cancer cells (p<0.05). On the other hand, CD166+ Panc-1 cells showed a significantly stronger colony formation activity than that of CD166- Panc-1 cells (p<0.05). In vivo analysis revealed that CD166+ cells elicited significantly greater tumor growth than that of CD166- cells (p<0.05) in both subcutaneous and orthotopic mouse tumor models. mRNA expression of the epithelial-mesenchymal transition activator Zeb1 was over-expressed in CD166- cells (p<0.001). Microarray analysis showed that TSPAN8 and BST2 were over-expressed in CD166+ cells, while BMP7 and Col6A1 were over-expressed in CD166- cells.

Conclusions

CD166+ pancreatic cancer cells are strongly tumorigenic, while CD166- pancreatic cancer cells exhibit comparatively stronger invasive and migratory activities. These findings suggest that CD166 expression is related to different functions in pancreatic cancer cells.