Biomechanical investigation of long spinal fusion models using three-dimensional finite element analysis.

BACKGROUND: This study represents the first finite element (FE) analysis of long-instrumented spinal fusion from the thoracic vertebrae to the pelvis in the context of adult spinal deformity (ASD) with osteoporosis. We aimed to evaluate the von Mises stress in long spinal instrumentation for models that differ in terms of spinal balance, fusion length, and implant type. METHODS: In this three-dimensional FE analysis, FE models were developed based on computed tomography images from a patient with osteoporosis. The von Mises stress was compared for three different sagittal vertical axes (SVAs) (0, 50, and 100 mm), two different fusion lengths (from the pelvis to the second [T2-S2AI] or 10th thoracic vertebra [T10-S2AI]), and two different types of implants (pedicle screw or transverse hook) in the upper instrumented vertebra (UIV). We created 12 models based on combinations of these conditions. RESULTS: The overall von Mises stress was 3.1 times higher on the vertebrae and 3.9 times higher on implants for the 50-mm SVA models than that for the 0-mm SVA models. Similarly, the values were 5.0 times higher on the vertebrae and 6.9 times higher on implants for the 100-mm SVA models than that for the 0-mm SVA models. Higher SVA was associated with greater stress below the fourth lumbar vertebrae and implants. In the T2-S2AI models, the peaks of vertebral stress were observed at the UIV, at the apex of kyphosis, and below the lower lumbar spine. In the T10-S2AI models, the peaks of stress were observed at the UIV and below the lower lumbar region. The von Mises stress in the UIV was also higher for the screw models than for the hook models. CONCLUSION: Higher SVA is associated with greater von Mises stress on the vertebrae and implants. The stress on the UIV is greater for the T10-S2AI models than for the T2-S2AI models. Using transverse hooks instead of screws at the UIV may reduce stress in patients with osteoporosis.

Clinical outcomes following total en bloc spondylectomy for spinal metastases from lung cancer.

BACKGROUND: The current guidelines for the treatment of non-small cell lung cancer encourage local curative treatment for selected patients with oligometastases. This study evaluated the surgical results of total en bloc spondylectomy (TES) for isolated spinal metastases originating from lung cancer in carefully selected patients. METHODS: We retrospectively reviewed 14 patients (7 men and 7 women) who underwent TES for spinal metastases originating from lung cancer between 2000 and 2017. The primary outcome measure was the postoperative overall survival time. The histological types included adenocarcinoma (n = 12), pleomorphic carcinoma (n = 1), and small cell lung carcinoma (SCLC) (n = 1 patient). We assessed postoperative survival using Kaplan-Meier analysis and the log-rank test. RESULTS: The median postoperative survival time was 83.0 months (6-162 months) in 13 patients with non-small cell lung carcinoma (NSCLC) and 6 months in 1 patient with SCLC. The 3-, 5-, and 10-year overall survival rates in patients with NSCLC were 61.5%, 53.8%, and 15.4%, respectively. Poor postoperative performance status (PS) and Frankel grade, and preoperative irradiation to the vertebrae to be resected were significantly associated with short-term survival after TES in patients with NSCLC (p < 0.05). CONCLUSIONS: The surgical results of TES for spinal metastases of lung cancer were relatively favorable among carefully selected patients. TES may be indicated for spinal metastases of lung cancer in patients with controlled primary lung cancer, NSCLC histology, prospect of good postoperative PS, and preferably no irradiation to the target vertebrae.

A randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab versus dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent, or persistent cervical carcinoma (JCOG1311): Primary analysis.

OBJECTIVE: To assess the efficacy and safety of dose-dense weekly paclitaxel plus carboplatin (ddTC) with or without bevacizumab compared to conventional, tri-weekly paclitaxel plus carboplatin (cTC) with or without bevacizumab, in metastatic or recurrent cervical carcinoma not amenable to curative local therapy. METHODS: Patients were randomly assigned to either the cTC or ddTC arm. The cTC regimen was paclitaxel 175 mg/m2 and carboplatin at an area under the curve (AUC) of 5 on day 1. The ddTC regimen was paclitaxel 80 mg/m2 on day 1, 8, 15 and carboplatin at AUC of 5 on day 1. Both cTC and ddTC treatments were repeated every 3 weeks for up to 9 cycles. After bevacizumab was approved in Japan, patients in both arms received bevacizumab 15 mg/kg if not contraindicated. The primary endpoint of phase II part was response rate (RR). If the RR of ddTC+bevacizumab was found to be at least 5% better than to cTC + bevacizumab, the study would proceed to phase III part, which had overall survival as its primary endpoint. CLINICAL TRIAL INFORMATION: jRCTs031180007. RESULTS: In total, 122 patients were randomly assigned to either the cTC arm (cTC + bevacizumab: 32; cTC:29) or the ddTC arm (ddTC+bevacizumab: 30; ddTC:31). The RR for patients on cTC + bevacizumab was 67.9%, and for patients on ddTC+bevacizumab 60.7%, cTC: 55.2%, and ddTC: 50.0%. CONCLUSIONS: The study did not meet the primary endpoint of phase II portion. Dose-dense, weekly paclitaxel plus carboplatin is not promising for metastatic or recurrent cervical carcinoma.

Radiation Disrupts the Protective Function of the Spinal Meninges in a Mouse Model of Tumor-induced Spinal Cord Compression.

BACKGROUND: Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. QUESTIONS/PURPOSES: To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier's ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier's ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? METHODS: Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier's ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson's trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 µm × 300 µm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss'κ coefficient. P values < 0.05 were considered statistically significant. RESULTS: There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15]; χ2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12]; χ2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 µm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. CONCLUSION: Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. CLINICAL RELEVANCE: We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.

The efficacy of surgical treatment on locomotive syndrome and physical function in patients with lumbar spinal canal stenosis.

BACKGROUND: Locomotive syndrome is a condition of reduced mobility due to problems with locomotive organs. Although lumbar spinal canal stenosis is one of the major diseases constituting locomotive syndrome, only few studies have focused on the association between the two pathologies. We aimed to investigate the effect of surgery on lumbar spinal canal stenosis with respect to locomotive syndrome using various physical function tests, including locomotive syndrome risk tests, before and after surgery. METHODS: Clinical data of 101 consecutive patients (male = 46; female = 55; mean age, 69.3 years) who underwent surgery for lumbar spinal canal stenosis at our institute were prospectively collected. Results of physical function tests, including stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale, and the sagittal vertical axis were evaluated before and 1 year after surgery. The association between several parameters and improvement of risk level in locomotive syndrome was evaluated. RESULTS: In the total assessment, 93.1% of cases were in stage 2 and 6.9% in stage 1 preoperatively, while 72.4% were in stage 2, 22.4% in stage 1, and 5.2% in stage 0 at 1 year postoperatively. Postoperative improvement in the total assessment was observed in 28.7% of cases. Several physical function tests and sagittal vertical axis showed significant improvement after surgery. On multiple logistic regression analysis, age >75 years (odds ratio = 10.9, confidence interval = 1.09-109) and postoperative sagittal vertical axis >40 mm (odds ratio = 17.8, confidence interval = 1.78-177) were significant risk factors associated with non-improvement in risk level of locomotive syndrome. CONCLUSIONS: Surgical treatment for lumbar spinal canal stenosis improved physical function, including locomotive syndrome. Risk factors associated with non-improvement of locomotive syndrome were later-stage elderly and postoperative sagittal balance impairment.

Abscopal Effect of Frozen Autograft Reconstruction Combined with an Immune Checkpoint Inhibitor Analyzed Using a Metastatic Bone Tumor Model.

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6-8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect.

Propensity score-matched analysis of systemic chemotherapy versus salvage hysterectomy for persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy.

BACKGROUND: The aim of the current study was to evaluate oncologic outcomes of patients who were treated with salvage hysterectomy (HT), compared to systemic chemotherapy (CT) for persistent cervical cancer after definitive radiotherapy (RT)/ concurrent chemoradiotherapy (CCRT). METHODS: Patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions from 2005 to 2014 were reviewed retrospectively (n = 317). Those who underwent a HT for persistent cervical cancer after definitive RT/CCRT were matched with propensity scores for patients who underwent systemic CT. Oncologic outcomes between the two groups using a propensity score matched-cohort analysis were compared. RESULTS: A total of 142 patients with persistent cervical cancer after definitive RT/CCRT were included after matching (HT: 71, systemic CT: 71). All background factors between HT and CT groups were well balanced. Median overall survival was 3.8 and 1.5 years in the HT and CT groups, respectively (p = 0.00193, hazards ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.73), Increasing residual tumor size was significantly associated with a high incomplete resection rate (p = 0.016, Odds Ratio 1.11, 95%CI 1.02-1.22). Severe late adverse events occurred in 7 patients (9.9%) in the HT cohort. CONCLUSION: The current study demonstrated that, when compared to systemic CT, the adoption of salvage HT for patients with persistent cervical cancer after definitive RT/CCRT reduced mortality rate by about 60%. This indicates that salvage HT could be curative treatment for those patients. Further prospective clinical trials with regard to salvage HT after RT/CCRT are warranted.

Clinical outcomes and survivals after total en bloc spondylectomy for metastatic leiomyosarcoma in the spine.

PURPOSE: Leiomyosarcoma (LMS) is generally resistant to radiation and chemotherapy. Our study aimed to examine the outcomes of total en bloc spondylectomy (TES) for spinal metastatic LMS and to analyze potential factors associated with survival. METHODS: This study included 10 consecutive patients who underwent TES for spinal metastatic LMS at our institute between 2005 and 2016 and were followed up at a minimum of 3 years after surgery. At the time of TES, all the 10 patients had solitary bone metastases in the spine. Seven patients had a lowered performance status (PS) with an eastern cooperative oncology group (ECOG) grade of 2 or 3 due to back pain or neurological symptoms. The cancer-specific survival (CSS) time from TES to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated using the Kaplan-Meier analysis and the log-rank test. RESULTS: Five patients underwent a single vertebral resection, and the other five patients underwent two or three consecutive vertebral resections. Three patients developed perioperative complications including pulmonary thromboembolism and pneumothorax. Nine patients improved or fairly maintained their PS with an ECOG grade of 1. The 1-, 3-, and 5-year CSS rates after TES were 90%, 70%, and 47%, respectively. Only postoperative disability (ECOG PS grade 3) was significantly associated with short-term survival after TES. CONCLUSIONS: The clinical outcomes of 10 patients who underwent TES for spinal metastatic LMS were favorable without severe complications. Postoperative disability was significantly associated with short-term survival after TES.

Revision surgery for instrumentation failure after total en bloc spondylectomy: a retrospective case series.

BACKGROUND: There have been several reports of instrumentation failure after three-column resections such as total en bloc spondylectomy (TES) for spinal tumors; however, clinical outcomes of revision surgery for instrumentation failure after TES are seldom reported. Therefore, this study assessed the clinical outcomes of revision surgery for instrumentation failure after TES. METHODS: This study employed a retrospective case series in a single center and included 61 patients with spinal tumors who underwent TES between 2010 and 2015 and were followed up for > 2 years. Instrumentation failure rate, back pain, neurological deterioration, ambulatory status, operation time, blood loss, complications, bone fusion after revision surgery, and re-instrumentation failure were assessed. Data were collected on back pain, neurological deterioration, ambulatory status, and management for patients with instrumentation failure, and we documented radiological bone fusion and re-instrumentation failure in cases followed up for > 2 years after revision surgery. RESULTS: Of the 61 patients, 26 (42.6%) experienced instrumentation failure at an average of 32 (range, 11-92) months after TES. Of these, 23 underwent revision surgery. The average operation time and intraoperative blood loss were 204 min and 97 ml, respectively. Including the six patients who were unable to walk after instrumentation failure, all patients were able to walk after revision surgery. Perioperative complications of reoperation were surgical site infection (n = 2) and delayed wound healing (n = 1). At the final follow-up, bone fusion was observed in all patients. No re-instrumentation failure was recorded. CONCLUSION: Bone fusion was achieved by revision surgery using the posterior approach alone.

[A Case of Bilateral Trigeminal Neuralgia and the Possible Onset Mechanisms Based on the Operative Findings].

Several cases of bilateral trigeminal neuralgia(TN)have been reported;however, the possible onset mechanism has rarely been discussed. We encountered a case of bilateral TN occurring in two stages. A 64-year-old woman presented with left TN. Magnetic resonance imaging showed the transverse pontine vein adhering to the left trigeminal root and superior cerebellar artery adhering to the right trigeminal root;however, no symptoms were noted. Immediately after microvascular decompression(MVD)on the left side, TN disappeared completely. However, 2 years postoperatively, the patient presented with right TN. The second MVD surgery revealed that the right cerebellar surface severely adhered to the dura mater, particularly under the surface of the tentorium. The arachnoid membrane at the cerebellopontine angle was slightly adhered. The patient was completely free from pain after the second MVD. The intraoperative findings suggested that the brain stem may have shifted and the cerebellopontine cistern may have narrowed because of cerebellar adhesion to the surrounding structures and arachnoid adhesion. We speculate that such structural changes in the posterior fossa after the first operation may have caused the asymptomatic vascular adhesion to change into the symptomatic offending adhesion over time.

A randomized phase II/III trial of conventional paclitaxel and carboplatin with or without bevacizumab vs dose-dense paclitaxel and carboplatin with or without bevacizumab, in stage IVB, recurrent or persistent cervical carcinoma: Japan Clinical Oncology Group Study (JCOG1311).

A randomized controlled trial has been initiated to compare chemotherapy containing dose-dense paclitaxel plus carboplatin with or without bevacizumab to a conventional regimen containing tri-weekly paclitaxel plus carboplatin with or without bevacizumab. Eligible patients are those with stage IVB, recurrent or persistent cervical carcinoma not amenable to curative treatment with local therapy. Patients are randomly assigned to either the conventional or dose-dense regimen. However, patients who are at increased risk of adverse events following bevacizumab administration will not receive this drug. The primary endpoint of phase II part is response rate. If the response rate of the dose-dense regimen is better than that of conventional regimen, this study will proceed to phase III, where the primary endpoint is overall survival. Secondary endpoints in phase III part are progression-free survival, response rates, adverse events, serious adverse events and the proportion of non-hospitalization periods compared with planned treatment periods.

Total spondylectomy for Enneking stage III giant cell tumor of the mobile spine.

PURPOSE: We reported the surgical outcomes of total en bloc spondylectomy (TES) with intralesional T-saw transpedicular osteotomy in patients with Enneking stage III spinal giant cell tumors (GCTs). METHODS: The medical records and imaging and pathological studies of 25 consecutive patients with Enneking stage III spinal GCTs undergoing surgery at our institution who were followed for at least 2 years were retrospectively reviewed. RESULTS: Eight men and 17 women (mean age: 34.2 years, range 16-51 years, at the time of surgery) were included. Six patients underwent previous tumor excision at another hospital, and one patient had a history of denosumab treatment. The GCTs were at the cervical, thoracic, and lumbar levels in three, nine, and 13 patients, respectively. TES was performed in 13 patients; 12 required intralesional pediculotomy. The remaining patients underwent total piecemeal spondylectomy with further intralesional tumor resection. During a mean follow-up of 99.2 months (range 24-216), two patients who underwent total piecemeal spondylectomy had local tumor recurrence, but no patients who underwent TES with intralesional pediculotomy had recurrence. The 2- and 10-year recurrence-free survival rates of patients treated with total piecemeal spondylectomy were 91.7% and 78.6%, respectively, while those of patients treated with TES were both 100%. CONCLUSIONS: TES with intralesional pediculotomy had a good surgical outcome even in patients with Enneking stage III spinal GCT, suggesting that minimal intralesional procedures could radically cure spinal GCTs. These slides can be retrieved under Electronic Supplementary Material.

Null model approaches to evaluating the relative role of different assembly processes in shaping ecological communities.

Various local processes simultaneously shape ecological assemblages. ß-diversity is a useful metric for inferring the underlying mechanisms of community assembly. However, ß-diversity is not independent of γ-diversity, which may mask the local mechanisms that govern community processes across regions. Recent approaches that rely on an abundance-based null model could solve this sampling issue. However, if abundance varies widely across a region, the relative roles of deterministic and stochastic processes may be substantially misestimated. Furthermore, there is additional uncertainty as to whether null models used to correct γ-dependence in ß-diversity should be independent of the observed patterns of species abundance distributions or whether the models should reflect these patterns. Here, we aim to test what null models with various constraints imply about the underlying processes shaping ß-diversity. First, we found that an abundance-driven sampling effect could substantially influence the calculation of γ-corrected ß-diversity. Second, we found that the null models that preserve the species abundance patterns could better reflect empirical patterns of spatial organization of individuals. The different implications generated from different applications of the null model approach therefore suggest that there are still frontiers regarding how local processes that shape species assemblages should be quantified. Carefully exploring each facet within different assembly processes is important.

[A Patient with Recurrent Ovarian Cancer Who Was Hypersensitive to Carboplatin Exhibited Complete Response to Gemcitabine and Nedaplatin].

A 57-year-old multiparous woman with FIGO stage IV ovarian cancer underwent primary surgery and was administered postoperative chemotherapy consisting of paclitaxel and carboplatin (TC). Complete response was confirmed on computed tomography. After a 20-month platinum free interval (PFI), an elevated serum CA125 level and recurrence in the peritoneum were confirmed, and she was retreated with TC as second-line chemotherapy. A hypersensitivity reaction occurred after administering the second dose of carboplatin; therefore, carboplatin was changed to nedaplatin. Complete response was confirmed on computed tomography, and the serum CA125 level returned to normal. After an 8-month PFI, an elevated serum CA125 level and recurrence in the peritoneum and liver were confirmed, and she was treated with 6 cycles of combination chemotherapy consisting of gemcitabine (1,000 mg/m2: day 1 and 8 q3 weeks)and nedaplatin (80 mg/m2: day 1 q3 weeks). Only cytopenia (grade 2: CTCAE v4.0) was noted as a complication during chemotherapy. Complete response was confirmed on computed tomography. This report presents the case of a patient with recurrent ovarian cancer who was platinum sensitive and successfully treated with gemcitabine and nedaplatin after showing a hypersensitivity reaction to carboplatin.

Discrepancies of fungi and plants in the pattern of beta-diversity with environmental gradient imply a comprehensive community assembly rule.

Beta-diversity partitioning has shown that the nestedness component is developed with environmental stress in a variety of taxa. However, soil fungal community may maintain its turnover components in contrast to the development of plants' nestedness component, and the potential causes remain unclear. To investigate the process of species turnover of soil fungi along a stress gradient in the Arctic, we divided species turnover component into sub-components: ßsim_hete and ßsim_homo representing species turnover with and without a change in the guilds, respectively. The results indicate that fungal communities maintain their turnover components, unlike plant communities; however, their ßsim_hete increased under stressful conditions. Additionally, GDM analysis showed that ßsim_hete was mainly explained by stress gradient and plant nestedness, suggesting that the functionality of soil fungi was ecologically filtered by environmental stress and plant community structure. The discordant trend of beta-diversity values between plant and fungi (i.e. development of plant nestedness and maintenance of fungal turnover) is possibly not caused by different assembly rules working in parallel on the two taxa, but according to an ecological rule that reflects plant-fungal interaction.

Vegetation as a key driver of the distribution of microbial generalists that in turn shapes the overall microbial community structure in the low Arctic tundra.

Understanding the variability of microbial niches and their interaction with abiotic and biotic factors in the Arctic can provide valuable insights into microbial adaptations to extreme environments. This study investigates the structure and diversity of soil bacterial communities obtained from sites with varying vegetation coverage and soil biogeochemical properties in the low Arctic tundra and explores how bacteria interact under different environmental parameters. Our findings reveal differences in bacterial composition and abundance among three bacterial niche breadths (specialists, common taxa, and generalists). Co-occurrence network analysis revealed Rhizobiales and Ktedonobacterales as keystone taxa that connect and support other microbes in the habitat. Low-elevation indicators, such as vascular plants and moisture content, were correlated with two out of three generalist modular hubs and were linked to a large proportion of generalists' distribution (18%). Structural equation modeling revealed that generalists' distribution, which influenced the remaining microbial communities, was mainly regulated by vegetation coverage as well as other abiotic and biotic factors. These results suggest that elevation-dependent environmental factors directly influence microbial community structure and module formation through the regulation of generalists' distribution. Furthermore, the distribution of generalists was mainly affected by macroenvironment filtering, whereas the distribution of specialists was mainly affected by microenvironment filtering (species-engineered microbial niche construction). In summary, our findings highlight the strong top-down control exerted by vegetation on generalists' distribution, which in turn shapes the overall microbial community structure in the low Arctic tundra.

Atlantoaxial Stabilization Using C1 Lateral Mass and C2 Pedicle/Translaminar Screw Fixation by Intraoperative C1- and C2-Direct-Captured Navigation with Preoperative Computed Tomography Images.

In C1-C2 posterior fixation, the C1 lateral mass and C2 pedicle/translaminar screw insertion under spine navigation have been used frequently. To avoid the risk of neurovascular damage in atlantoaxial stabilization, we assessed the safety and effectiveness of a preoperative computed tomography (CT) image-based navigation system with intraoperative independent C1 and C2 vertebral registration. It is ideal when a reference frame can be linked directly to the C1 posterior arch for C1-direct-captured navigation, but there is a mechanical challenge. A new spine clamp-tracker system was implemented recently, which allows reliable C1- and C2- direct-captured navigation in nine patients with traumatic C2 fractures. In this way, there was no misalignment of C1-C2 screws. C1 lateral mass screws were used except for one case, and translaminar screws were primarily used as an anchor for C2. The C1 lateral mass screw locations, which are 19 mm laterally from the C1 posterior arch's center, are taken to be constant. However, there is one unusual circumstance in which using a C1 laminar hook instead of a C1 lateral mass screw appears to be a beneficial substitute. The increase of surgical accuracy for posterior C1-C2 screw fixation without cost constraints is significantly facilitated by intraoperative C1- and C2-direct-captured navigation with preoperative computed CT images.

A multi-institutional phase II trial of paclitaxel and carboplatin in the treatment of advanced or recurrent cervical cancer.

OBJECTIVE: The aim of this prospective trial was to evaluate the efficacy and safety of the combination of paclitaxel and carboplatin (TC) in patients with metastatic or recurrent cervical cancer. METHODS: This was a multicenter phase II trial of 3 weekly paclitaxel 175 mg/m(2) 3-hour iv day 1 followed by carboplatin AUC5 1-hour iv day 1 for maximum of 6 cycles until disease progression or prohibitive toxicity. Eligible patients had squamous or adenocarcinoma of the cervix with measurable stage IVB or recurrent, aged 20-75 years, Eastern Cooperative Oncology Group performance status 0-2, prior platinum-containing regimen 0-1, and no prior taxane. The primary endpoint was overall response rate (ORR) by RECIST. RESULTS: 41 patients were enrolled, of which 39 were evaluable for analysis. 33 patients (84.6%) received prior radiotherapy. The confirmed ORR was 59% (95% CI, 43% to 75%); 5 patients (13%) achieved a complete response and median response duration was 5.2 months. The response rates for patients who had adenocarcinoma (n=10) and prior platinum-based chemotherapy<6 months (n=7) were 40.0% and 0%, respectively. The median progression-free survival and overall survival times were 5.3 and 9.6 months, respectively. The most frequent grade 3 or 4 adverse events were neutropenia (79%), anemia (46%), thrombocytopenia (15%), and fatigue (8%). No treatment-related death was seen. CONCLUSIONS: TC seemed to be feasible and effective similar to other cisplatin-based doublets for the treatment of metastatic or recurrent cervical cancer. Phase III trial is warranted to establish the clinical benefits of this combination.

Phase II study of concurrent chemoradiotherapy with high-dose-rate intracavitary brachytherapy in patients with locally advanced uterine cervical cancer: efficacy and toxicity of a low cumulative radiation dose schedule.

OBJECTIVE: A multicenter phase II trial was conducted to assess the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with high-dose-rate intracavitary brachytherapy (HDR-ICBT) using a low cumulative prescribed dose schedule in patients with locally advanced uterine cervical cancer. METHODS: The Japanese Gynecologic Oncology Group (JGOG) study JGOG1066 enrolled patients with FIGO stages III-IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by CT. Patients received definitive radiotherapy (RT) consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62-65 Gy prescribed at point A. Cisplatin 40 mg/m(2) weekly was administered concurrently with RT for 5 courses. RESULTS: Of the 72 patients registered, 71 were eligible. With a median follow-up of 28 months, the 2-year progression-free survival rate and pelvic disease progression-free rate were 66% (95% CI, 54% to 76%) and 73% (95% CI, 61% to 82%), respectively. Progression-free survival decreased significantly with increased central tumor size (P=0.036). The 2-year cumulative late complication rates were 24% for all grades, 9% for grade 1, 12% for grade 2, 3% for grade 3, and 0 for grades 4/5. CONCLUSIONS: The JGOG1066 demonstrated that CCRT using HDR-ICBT with a low cumulative RT dose schedule achieved comparable outcome as those achieved with global dose schedules (EQD2=85 Gy) with a lower incidence of late toxicity for locally advanced uterine cervical cancer in a Japanese population.

Feasibility and acute toxicity of Concurrent Chemoradiotherapy (CCRT) with high-dose rate intracavitary brachytherapy (HDR-ICBT) and 40-mg/m2 weekly cisplatin for Japanese patients with cervical cancer: results of a Multi-Institutional Phase 2 Study (JGOG1066).

OBJECTIVE: To assess the feasibility and acute toxicity of concurrent chemoradiotherapy (CCRT) with high-dose rate intracavitary brachytherapy (HDR-ICBT) and standard dose delivery of cisplatin for Japanese patients with cervical cancer. MATERIALS AND METHODS: The phase 2 study included Japanese patients with International Federation of Gynecology and Obstetrics stage III to IVA uterine cervical cancer who had no para-aortic lymphadenopathy (>10 mm) assessed by computed tomography. Patients were 20 to 70 years of age and had Eastern Cooperative Oncology Group performance status of 0 to 1. The radiotherapy protocol consisted of whole-pelvis external beam radiotherapy and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 62 to 65 Gy prescribed at point A. Cisplatin was administered weekly at a dose of 40 mg/m(2) for 5 courses. RESULTS: Between March 2008 and January 2009, 72 patients from 25 institutions were enrolled, and 71 patients were eligible and evaluable for compliance and severe toxicity. The median age of the patients was 57 years (range, 32-70 years). Sixty-five patients (92%) received the planned 5 courses of chemotherapy. Four patients had cisplatin dose reduction according to the protocol. Radiotherapy was completed per protocol in 68 patients (96%). Median overall treatment time was 50 days (range, 37-66 days). The following grade 3 or 4 acute adverse events were observed: neutropenia in 31 patients (44%), anemia in 10 patients (14%), diarrhea in 4 patients (6%), and anorexia in 3 patients (4%). CONCLUSIONS: Concurrent chemoradiotherapy with HDR-ICBT and standard weekly delivery of cisplatin was feasible with acceptable toxicity in Japanese patients with cervical cancer.