Nipple reconstruction using spiral-peeling technique during oncoplastic breast-conserving surgery for a patient with small breasts.

Treatment of early breast cancer using breast-conserving surgery (BCS) commonly leads to local control and acceptable cosmetic results. We report a useful technique to achieve symmetry of the breast shape and nipple-areola, with excellent results. A Japanese patient with early breast cancer located in the inner central area of the breast was enrolled in this study. Intraductal spread of breast cancer to the nipple was suspected; however, no invasion was observed outside the nipple wall. We preserved the cylindrical surface, but resected the inner tissue with the top surface of the nipple. After coring the nipple, the remnant cylindrical surface was cut into a spiral shape. Nipple reconstruction using the spiral-peeling technique during oncoplastic breast-conserving surgery (OPBCS) may be useful for patients who desire nipple preservation.

Primary Cilia Are Frequently Present in Small Cell Lung Carcinomas but Not in Non-Small Cell Lung Carcinomas or Lung Carcinoids.

Most human malignant neoplasms show loss of primary cilia (PC). However, PC are known to be retained and involved in tumorigenesis in some types of neoplasms. The PC status in lung carcinomas remains largely uninvestigated. In this study, we comprehensively assessed the PC status in lung carcinomas. A total of 492 lung carcinomas, consisting of adenocarcinomas (ACs) (n = 319), squamous cell carcinomas (SCCs) (n = 152), and small cell lung carcinomas (SCLCs) (n = 21), were examined by immunohistochemical analysis using an antibody against ARL13B, a marker of PC. The PC-positive rate was markedly higher in SCLCs (81.0%) than in ACs (1.6%) and SCCs (7.9%). We subsequently performed analyses to characterize the PC-positive lung carcinomas further. PC-positive lung carcinomas were more numerous and had longer PC than normal cells. The presence of PC in these cells was not associated with the phase of the cell cycle. We also found that the PC were retained even in metastases from PC-positive lung carcinomas. Furthermore, the hedgehog signaling pathway was activated in PC-positive lung carcinomas. Because ARL13B immunohistochemistry of lung carcinoids (n = 10) also showed a statistically significantly lower rate (10.0%) of PC positivity than SCLCs, we searched for a gene(s) that might be upregulated in PC-positive SCLCs compared with lung carcinoids, but not in PC-negative carcinomas. This search, and further cell culture experiments, identified HYLS1 as a gene possessing the ability to regulate ciliogenesis in PC-positive lung carcinomas. In conclusion, our findings indicate that PC are frequently present in SCLCs but not in non-SCLCs (ACs and SCCs) or lung carcinoids, and their PC exhibit various specific pathobiological characteristics. This suggests an important link between lung carcinogenesis and PC.

Clinicopathological Characteristics and Mutational Landscape of APC, HOXB13, and KRAS among Rwandan Patients with Colorectal Cancer.

Cancer research in Rwanda is estimated to be less than 1% of the total African cancer research output with limited research on colorectal cancer (CRC). Rwandan patients with CRC are young, with more females being affected than males, and most patients present with advanced disease. Considering the paucity of oncological genetic studies in this population, we investigated the mutational status of CRC tissues, focusing on the Adenomatous polyposis coli (APC), Kirsten rat sarcoma (KRAS), and Homeobox B13 (HOXB13) genes. Our aim was to determine whether there were any differences between Rwandan patients and other populations. To do so, we performed Sanger sequencing of the DNA extracted from formalin-fixed paraffin-embedded adenocarcinoma samples from 54 patients (mean age: 60 years). Most tumors were located in the rectum (83.3%), and 92.6% of the tumors were low-grade. Most patients (70.4%) reported never smoking, and 61.1% of patients had consumed alcohol. We identified 27 variants of APC, including 3 novel mutations (c.4310_4319delAAACACCTCC, c.4463_4470delinsA, and c.4506_4507delT). All three novel mutations are classified as deleterious by MutationTaster2021. We found four synonymous variants (c.330C>A, c.366C>T, c.513T>C, and c.735G>A) of HOXB13. For KRAS, we found six variants (Asp173, Gly13Asp, Gly12Ala, Gly12Asp, Gly12Val, and Gln61His), the last four of which are pathogenic. In conclusion, here we contribute new genetic variation data and provide clinicopathological information pertinent to CRC in Rwanda.

Evaluation of the widths of the mucosal strips in pathological examination of specimens of endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer in Japan. Pathological evaluation of ESD specimens is considered essential to determine if additional gastrectomy is necessary. Usually, specimens resected by ESD are sliced into 2-3 mm wide sections, and each section is examined for depth of tumor and lymphovascular invasion. Nevertheless, in most cases of additional gastrectomy, lymph node metastasis is not present. Given that there are few-studies on how clinical-decisions based on the pathologic-evaluation-method, in particular the specimen cut-width, influence patient outcomes, we retrospectively evaluated whether reducing the number of cuts to one-half or one-third would result in underestimation of the real need for additional surgery. The effect of the actual cut-width on recommended treatment (referral to operation) and patient-outcomes was also assessed. METHODS: Pathological records of 498 lesions from 439 patients were reviewed and re-evaluated. All pathological descriptions are based on the gastric cancer classification system of the Japanese Gastric Cancer Association, 15th edition. RESULTS: In 5.8% and 8.5% of the total specimens, underdiagnosis of tumor-depth and lymphovascular invasion occurred when the number of sections was reduced to one-half and one-third, respectively. Significantly more submucosal invasions were found in the group in which the cut-with was between 3 and 4 mm than in the group in which the cut width was less than 3 mm. CONCLUSION: Evaluation of the appropriate cut-width is important and should be discussed from the standpoint of labor costs and lost opportunities to search for molecular markers in ESD materials.

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.

The influence of costal resection on pulmonary function after total en bloc spondylectomy for spine tumor.

BACKGROUND: Total en bloc spondylectomy (TES) is one of the surgical procedures which has been recognized as a complete resection for spine tumors. Although the surgery achieves favorable local control for solitary spinal lesion, performing the procedure in the thoracic spine requires circumferential dissection around the vertebral body and bilateral rib resections which might result in decline of pulmonary function postoperatively. This study aimed to clarify whether the number of rib resections negatively impacts pulmonary function after the procedure. METHODS: This study included 31 patients who underwent vertebrectomy (17 males and 14 females) with a mean age of 54.2 years. Pulmonary function testing (PFT) was performed before surgery and at 1 month, 6 months, and 1 year postoperative visits. Patients with restrictive disorders such as space occupying lesions in the lung, obstructive problems such as a history of asthma, and smoking history were excluded from this study. Associations between the number of rib resections and PFT data were analyzed based on the resected level of the thoracic spine. RESULTS: There was a significant decrease in forced vital capacity (FVC) at 1 month (72% of preoperative value), followed by gradual recovery at 6 months (89%) and 1 year (90%). The percentage of predicted forced expiratory volume in 1 s remained stable. Patients who underwent three pairs of rib resections showed a significant decrease in the FVC (83.5% of the preoperative value) and FEV1 (82.1% of the preoperative value) compared with one or two pairs of rib resections. CONCLUSION: FVC decreased 1 month after vertebrectomy and returned to 90% of preoperative value at 1 year postoperatively. Three pairs of rib resections showed a significant decrease in FVC, suggesting the influence of a greater numbers of rib resections on pulmonary function.

The prevalence of locomotive syndrome and its associated factors in patients with Type 2 diabetes mellitus.

OBJECTIVES: We investigated the prevalence of locomotive syndrome (LS) and related musculoskeletal diseases [osteoarthritis (OA), lumbar spondylosis, and spinal alignment] in Type 2 diabetes mellitus (DM) patients. METHODS: Clinical data were collected from 101 patients (55 males; 46 females) admitted to our hospital for diabetes education from October 2018 to April 2021. Patients underwent full-spine and whole-legs standing radiography and physical measurements (10-m walking and grip strength tests and three LS risk tests). RESULTS: The estimated prevalence of LS was 86.1% (Stage 1: 44.5%, Stage 2: 41.6%), lumbar spondylosis was 11.9%, and hip, knee, and ankle OA were 16.9%, 51.5%, and 12.9%, respectively. Multiple logistic regression analysis identified grip strength [odds ratio (OR) = 0.89, confidence interval (CI) = 0.83-0.94], diabetic retinopathy (OR = 5.85, CI = 1.64-20.78), knee OA (OR = 3.34, CI = 1.11-10.02), and a sagittal vertical axis >40 mm (OR = 3.42, CI = 1.13-10.39) as significantly associated risk factors for worsening LS in Type 2 DM patients. CONCLUSIONS: This study clarified the epidemiological indicators of LS and associated factors in DM patients. Exercise therapy and DM management are effective strategies to reduce the occurrence and progression of LS.

Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation.

Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron-microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC-positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC-positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC-positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Tumor-Specific Immunoenhancing Effects after Local Cryoablation for Metastatic Bone Tumor in a Mouse Model.

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD.

Evaluation of locomotive syndrome in patients receiving surgical treatment for degenerative musculoskeletal diseases: A multicentre prospective study using the new criteria.

OBJECTIVES: This study aimed to evaluate the condition of patients with locomotive syndrome (LS) and their improvement after undergoing surgery for degenerative musculoskeletal diseases using the new criteria, including stage 3. METHODS: In total, 435 patients aged ≥40 years (167 middle-aged and 268 older) were divided into four groups based on the disease location: the lumbar (n = 118), hip (n = 191), knee (n = 80), and foot and ankle (n = 46) groups. Patients were evaluated by pre- and 1 year postoperative LS risk tests, including the stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale. RESULTS: The pre- and postoperative prevalence of LS stage 3 were 78% and 29%, respectively. The postoperative LS stage improved in 62% of patients (77% and 53% in the middle-aged and older groups, respectively). Overall, the knee group showed the worst results, and the foot and ankle groups showed the best pre- and postoperative results. The pre- and postoperative prevalence of LS stage 3 according to the 25-Question Geriatric Locomotive Function Scale were comparable to those based on the total assessment. CONCLUSIONS: The new LS stage criteria are appropriate, and the 25-Question Geriatric Locomotive Function Scale is a good option for evaluating patients requiring surgery.

Clinical outcomes and prognostic factors following the surgical resection of renal cell carcinoma spinal metastases.

The efficacy of surgical resection in metastatic renal cell carcinoma is an active and important research field in the postcytokine era. Bone metastases, especially in the spine, compromise patient performance status. Metastasectomy is indicated, if feasible, because it helps to achieve the best clinical outcomes possible compared with other treatments. This study examined the postoperative survival and prognostic factors in patients who underwent metastasectomy of spinal lesions. The retrospective study included 65 consecutive patients with metastatic renal cell carcinomas who were operated on by spinal metastasectomy between 1995 and 2017 at our institution. The cancer-specific survival times from the first spinal metastasectomy to death or the last follow-up (≥3 years) were determined using Kaplan-Meier analysis. Potential factors influencing survival were analyzed using Cox proportional hazard models. Planned surgical resection of all the spine tumors was achieved in all patients. Of these, 38 had complete metastasectomy of all visible metastases, including extraspinal lesions. In all patients, the estimated median cancer-specific survival time was 100 months. The 3-, 5-, and 10-year cancer-specific survival rates were 77%, 62%, and 48%, respectively. The survival times after spinal metastasectomy were similar in both cytokine and postcytokine groups. In multivariate analyses, postoperative disability, the coexistence of liver metastases, multiple spinal metastases, and incomplete metastasectomy were significant risk factors associated with short-term survival. Complete metastasectomy, including extraspinal metastases, was associated with improved cancer-specific survival. Proper patient selection and complete metastasectomy provide a better prognosis in metastatic renal cell carcinoma patients.

Surgical Metastasectomy in the Spine: A Review Article.

BACKGROUND: The use of surgical metastasectomy (SM) has increased across cancer types in recent decades despite the increasing efficacy of modern systemic treatment modalities. Symptomatic spinal metastases severely compromise patients' performance status. However, as spinal SM is a complex surgery with potentially significant complications, it is not considered the treatment of choice. METHODS: We reviewed the articles on SM in several primary cancers with different types of metastatic lesions and extracted the data from relevant articles to provide a comprehensive review including the surgical techniques, indications, reported outcomes, and future prospects of SM in spinal metastases. RESULTS: Total en bloc spondylectomy (TES) is a method of spinal SM associated with a lower risk of tumor recurrence and complications. Intralesional transpedicular osteotomy using a fine threadwire saw allows prevention of spinal cord and nerve root injuries. Spinal SM is considered suitable for patients with controlled primary disease having no evidence of disseminated extraspinal metastases, a completely resectable solitary lesion in the spine, and adequate cardiopulmonary reserve to tolerate the surgery. Metastatic lesions from kidney and thyroid cancers have been reported as the best candidates for spinal SM. Although data about spinal SM are limited, the reported outcomes are favorable with acceptable local recurrence rates in long-term follow-up. CONCLUSION: In patients with isolated resectable spinal metastases, complete SM including TES is a useful option as it can improve function and survival. However, appropriate patient selection and surgical feasibility remain the most important aspects of management. IMPLICATIONS FOR PRACTICE: Surgical metastasectomy for spinal metastases may be a potentially curative treatment option with a low risk of local recurrence and lead to prolonged long-term survival if appropriate patients are selected and if the surgery is carried out by experienced surgeons in high-volume centers.

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.

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.

Risk factors for poor outcomes of early rehabilitation after total en bloc spondylectomy: a retrospective chart review of 140 patients.

STUDY DESIGN: A retrospective chart review. OBJECTIVES: Total en bloc spondylectomy (TES) has been reported to decrease the rate of local recurrence and increase survival. Although it is important to achieve early recovery of physical functions after surgery, no studies have evaluated rehabilitation outcomes during the acute phase after TES. This study evaluated ambulatory functions and activities of daily living (ADLs) after surgery and analyzed the prognostic significance of variables affecting rehabilitation outcomes at 1 month after TES. SETTING: University hospital in Kanazawa, Japan. METHODS: This study included 140 patients with spinal tumors who underwent TES between April 2010 and April 2017. Demographic characteristics, neurological functions, perioperative complications functional status as measured by the Functional Independent Measure, and independent indoor walking based on the Spinal Cord Independent Measure were extracted from medical records. Multivariate analyses were performed to assess factors associated with the recovery of ambulation and ADL at 1 month after TES. RESULTS: Preoperative neurological deficits were observed in 51 patients (36%), and postoperative neurological deterioration was found in 41 patients (29%). Multivariate analyses indicated that preoperative neurological deficits (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.07-15.99), postoperative cerebrospinal fluid leakage (OR, 13.42; 95% CI, 2.93-78.82), surgical site infections (OR, 15.27; 95% CI, 2.26-127.7), and postoperative neurological deterioration (OR, 4.86; 95% CI, 1.33-19.99) were risk factors for walking ability and recovery of ADL (P < 0.01). CONCLUSIONS: This study identified preoperative neurological dysfunction and perioperative complications as independent risk factors for poor recovery of ambulation and ADL early after TES.

Improvement of locomotive syndrome with surgical treatment in patients with degenerative diseases in the lumbar spine and lower extremities: a prospective cohort study.

BACKGROUND: The epidemiology, risk factors, and prevention of locomotive syndrome (LS) have been reported. However, the number of clinical studies about the efficacy of LS treatment, including surgery, has been limited. This study aimed to evaluate LS and its improvement in patients undergoing surgeries for degenerative disease of the lumbar spine and lower extremities, and to discuss the effects of surgery on LS and the issues of LS assessment in these patients. METHODS: We enrolled 257 patients aged ≥60 years that underwent surgery for degenerative diseases of the lumbar spine and lower extremities and agreed to participate in the preoperative and 6- and 12-month postoperative LS examinations. According to the disease location, patients were divided into the lumbar (n = 81), hip (n = 106), knee (n = 43), and foot and ankle (n = 27) groups. Patients underwent LS risk tests, including the stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale (GLFS-25) assessment. RESULTS: The preoperative prevalence of LS stage 2 was 95%. Only the hip group showed significant improvements in the stand-up test. The knee group showed the worst results in the stand-up and two-step tests at all time points. All four groups had significant improvements in GLFS-25 scores. Approximately 40% of all patients had improvement in their LS stage postoperatively. However, > 90% of the patients in the knee group had LS stage 2 postoperatively. CONCLUSION: Nearly all elderly patients requiring surgeries for degenerative diseases of the lumbar spine and lower extremities had advanced conditions (LS stage 2). Surgeries could be beneficial in alleviating LS. The LS stage 3 criteria should be established, and the use of the GLFS-25 assessment can be appropriate for advanced LS patients with severe musculoskeletal diseases requiring surgeries.

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.

Abdominal trunk muscle weakness and its association with chronic low back pain and risk of falling in older women.

BACKGROUND: Previous studies have indicated that trunk muscle strength decreases with chronic low back pain, and is associated with poor balance, poor functional performance, and falls in older adults. Strengthening exercises for chronic low back pain are considered the most effective intervention to improve functional outcomes. We developed an innovative exercise device for abdominal trunk muscles that also measures muscle strength. The correlation between muscle weakness, as measured by our device, the presence of chronic low back pain, and decreased physical ability associated with a risk of falling were evaluated in older women. METHODS: Thirty-eight elderly women, who could walk without support during daily activities and attended our outpatient clinic for treatment of chronic low back pain, knee or hip arthritis, or osteoporosis, were included in this study. Anthropometric measurements were performed. Grip power and one-leg standing time with eyes open were measured, and abdominal trunk muscle strength was measured using our device. History of falling in the previous 12 months was noted. Subjects with chronic low back pain (visual analog scale score ≥ 20 mm) for over 3 months were assigned to the low back pain group (n = 21). The remaining subjects formed the non-low back pain group (n = 17). RESULTS: Abdominal muscle strength of subjects in the low back pain group, and with history of falling, was significantly lower compared with that of subjects in the non-low back pain group, and in subjects without a history of falling, respectively. There was a moderate positive correlation between abdominal trunk muscle strength and one-leg standing time with eyes open. CONCLUSION: We measured abdominal muscle strength in older women with chronic low back pain using our device, and it was significantly lower than that of those without chronic low back pain. Muscle weakness was associated with a history and risk of falling.