Using the combined C-reactive protein and controlling nutritional status index for elderly non-small cell lung cancer.

Background: We found that conventional controlling nutritional status (CONUT) score can serve as a sensitive prognostic marker. Some prognostic indicators do include C-reactive protein (CRP), such as the CRP-lymphocyte ratio (CLR), CRP-albumin-lymphocyte index (CALLY), and CRP-albumin ratio (CAR). However, CRP has not been combined with the CONUT score, which we believe could result in a more sensitive marker. This study evaluated the combined use of the CONUT score and CRP to predict prognostic outcomes in elderly non-small cell lung cancer (NSCLC) patients undergoing surgical resection. Methods: This study involved the retrospective analysis of 114 NSCLC patients who were over 80 years old and underwent curative resection. The summation of the CRP score and CONUT score was defined as the combined CRP and controlling nutritional status (C-CONUT) score. The capacity of CRP, CONUT score, and C-CONUT score to predict overall survival (OS) was evaluated via receiver operating characteristics (ROC) curves. Prognostic markers for OS were then identified using the Cox proportional hazards regression model. Results: The ROC curves identified the C-CONUT score as the most reliable marker of prognosis (area under the curve =0.745). Forty-seven patients were included in the high C-CONUT (≥3) group, while 67 patients were included in the low C-CONUT (0 to 2) group. Worse prognosis rates were observed in the high C-CONUT group in comparison to the low C-CONUT group in terms of OS (five-year OS: 39.8% versus 87.4%, P<0.001). Lymphatic invasion (P<0.001), histological findings (P=0.02), and C-CONUT score [hazard ratio (HR): 5.07, 95% confidence interval (CI): 2.39-10.8, P<0.001] were identified as exclusive markers for OS prognosis in the multivariate analysis. Conclusions: Our current findings indicate that C-CONUT score may serve as an innovative prognostic marker in the elderly NSCLC population.

Mean computed tomography value to predict spread through air spaces in clinical N0 lung adenocarcinoma.

BACKGROUND: The aim of this study was to assess the ability of radiologic factors such as mean computed tomography (mCT) value, consolidation/tumor ratio (C/T ratio), solid tumor size, and the maximum standardized uptake (SUVmax) value by F-18 fluorodeoxyglucose positron emission tomography to predict the presence of spread through air spaces (STAS) of lung adenocarcinoma. METHODS: A retrospective study was conducted on 118 patients those diagnosed with clinically without lymph node metastasis and having a pathological diagnosis of adenocarcinoma after undergoing surgery. Receiver operating characteristics (ROC) analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUVmax value to predict STAS. Univariate and multiple logistic regression analyses were performed to determine the independent variables for the prediction of STAS. RESULTS: Forty-one lesions (34.7%) were positive for STAS and 77 lesions were negative for STAS. The STAS positive group was strongly associated with a high mCT value, high C/T ratio, large solid tumor size, large tumor size and high SUVmax value. The mCT values were - 324.9 ± 19.3 HU for STAS negative group and - 173.0 ± 26.3 HU for STAS positive group (p < 0.0001). The ROC area under the curve of the mCT value was the highest (0.738), followed by SUVmax value (0.720), C/T ratio (0.665), solid tumor size (0.649). Multiple logistic regression analyses using the preoperatively determined variables revealed that mCT value (p = 0.015) was independent predictive factors of predicting STAS. The maximum sensitivity and specificity were obtained at a cutoff value of - 251.8 HU. CONCLUSIONS: The evaluation of mCT value has a possibility to predict STAS and may potentially contribute to the selection of suitable treatment strategies.

Prognostic Significance of CONUT Score in Elderly NSCLC.

PURPOSE: This study evaluated the Controlling Nutritional Status (CONUT) score as a prognostic predictor in elderly non-small cell lung cancer (NSCLC) patients with surgical resection. METHODS: Overall, 114 patients over 80 years old undergoing curative resection for NSCLC were retrospectively analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the capacity of immune-inflammatory markers to predict overall survival (OS). Cox-proportional hazards regression analysis was implemented to investigate prognostic markers for OS. RESULTS: Based on ROC curves, the CONUT score was found to be the most valuable prognostic marker (area under the curve = 0.716). The high CONUT (≥2) group included 54 patients, and the low CONUT (0 or 1) group included 60 patients. The high CONUT group had poorer prognosis rates compared to the low CONUT group with regard to OS (5-year OS: 46.3% vs. 86.0%, p = 0.0006). In the multivariate data analysis, histology, lymphatic invasion, and CONUT score (hazard ratio: 4.23, p = 0.0003) were found to be exclusive and independent prognostic markers for OS. CONCLUSION: Preoperatively, the CONUT score can be used as a novel prognostic marker in elderly NSCLC patients. CONUT evaluations can also be used to design nutritional interventions to improve patient outcomes.

[Indocyanine Green Fluorescence Intraoperative Imaging for Fistula Identification of Pleuroperitoneal Communication by Continuous Ambulatory Peritoneal Dialysis:Report of a Case].

A 64-year-old female with chronic renal failure had been receiving continuous ambulatory peritoneal dialysis (CAPD). She developed acute hydrothorax in the right pleural cavity 1 year after the commencement of CAPD. Scintigraphy revealed a diagnosis of pleuroperitoneal communication, and we performed video-assisted thoracoscopic surgery. We infused a dialysis solution containing indocyanine green (ICG) through CAPD catheter. Near-infrared fluorescence thoracoscopy revealed a fistula that could not be identified by white light. We sutured the fistula covered with a polyglycolic acid sheet and fibrin glue. The CAPD was able to be resumed 8 days after surgery, and there was no recurrence of pleural effusion 10 months since surgery. Identification of the diaphragmatic fistula is important in the treatment of pleuroperitoneal communication. This technique using near-infrared fluorescence thoracoscopy with ICG was useful in identifying the fistula, and it emitted sufficient fluorescence even at low concentration ICG.

Rapidly developing intrathoracic low-grade fibromyxoid sarcoma: A case report.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare mesenchymal tumor that primarily arises in the limbs and trunk of young adults, and rarely in the thoracic cavity. An 84-year-old Japanese woman presented with a right intrathoracic mass which was 8 cm in size. CT-guided needle biopsy did not provide a definitive diagnosis. Perioperatively, a mass was found in the right lower lobe of the lung and was suspected to have invaded the chest wall at the sixth-eighth ribs. A right lower lobectomy and combined chest wall resection were performed. Microscopic examination revealed that the tumor was a low-grade spindle cell tumor originating from the pleura demonstrating focal invasion of the lung. The tumor exhibited positivity for MUC4, and FUS gene translocation was confirmed through fluorescence in situ hybridization. Unfortunately, 10 months postoperatively, tumor recurrence was noted as peritoneal dissemination, and the patient passed away 13 months postoperatively. Although LGFMS may be diagnosed histologically as a low-grade tumor by needle biopsy, in this case, it was highly malignant. Postoperative long-term regular medical follow-up is recommended considering the highly malignant nature of the tumor and the high risk of local recurrence and pulmonary metastasis.

Combined treatment with beaded EWS, Gore-tex patch and N-butyl-2-cyanoacrylate for bronchial fistula: The novel "sandwich method".

An 84-year-old man underwent right basal segmentectomy for primary lung cancer and developed empyema accompanied by a bronchopleural fistula (BPF). Emergency open-window thoracotomy was performed. Although the general and nutritional conditions improved, the fistula did not close naturally, and we planned to close it 6 months after surgery. In this report, we describe, for the first time, a novel method for closing BPF using an endobronchial Watanabe spigot (EWS), polyglycolic acid (PGA) sheet and N-butyl-2-cyanoacrylate (NBCA). We named this method the"sandwich method."

Primary adrenal Ewing's sarcoma family of tumors with tumor thrombus of the inferior vena cava: a case report.

BACKGROUND: Ewing's sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing's sarcoma) caused by chromosomal translocations have been collectively termed Ewing's sarcoma family of tumors. We report a rare case of primary adrenal Ewing's sarcoma family of tumors with tumor thrombus. CASE PRESENTATION: A 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively. CONCLUSION: Radical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing's sarcoma family of tumors.

Psoas and Mediastinal Abscesses during Intravenous Tocilizumab Treatment in Multicentric Castleman Disease.

Tocilizumab has been used to treat idiopathic multicentric Castleman disease (iMCD). As tocilizumab prevents interleukin-6 from exerting pro-inflammatory effects, there is some concern about a delayed diagnosis of severe infections during tocilizumab treatment. Although serious infections during tocilizumab therapy have been previously described in patients with rheumatoid arthritis, they have not been reported in iMCD. We herein report a case of disseminated Staphylococcus aureus infection after a superficial skin wound followed by psoas and mediastinal abscesses with pyogenic spondylodiscitis in an iMCD patient with diabetes. Physicians should be alert for the occurrence of disseminated S. aureus infection after even minor skin injury during tocilizumab therapy.

Surgical ligation level of the bronchial artery influences tissue oxygen saturation of the bronchus and the incidence of postoperative bronchofistula after pulmonary lobectomy.

BACKGROUND: Lobectomy, or the removal of a lobe of the lung, is the most commonly performed lung cancer surgery. One of the most severe postoperative complications is a bronchial stump fistula, which often occurs following a right lower lobectomy. During lymph node dissection, the bronchial arteries, which supply blood to the bronchus, are cut. Subsequently, reduced blood supply to the bronchus may result in bronchofistula. We investigated the relationship between the level of the surgical ligation of the bronchial arteries and the decrease in blood flow at the bronchial stump during a right lower lobectomy. This study aimed to clarify the relationship between the anatomical amputation level of the bronchial artery and the decrease in tissue oxygen saturation at the bronchial stump, allowing us to identify a surgical procedure that reduces the risk of a bronchopleural fistula following pulmonary lobectomy and an appropriate bronchial artery amputation site that could be used in future lobectomies. METHODS: We developed a new system (micro-tissue oxygen saturation) that enabled the semi-quantification of the oxygen saturation of thin tissues in pinpoint during video-assisted thoracic surgery. Changes in the blood flow at the bronchial stump were examined during lymph node dissection and bronchial artery amputation using a biological pig lobectomy model. RESULTS: The regional oxygen saturation level at the bronchial wall was 95.5%±1.0% in normal conditions. A gradual decrease in regional oxygen saturation was observed, as the cutting point of the bronchial artery was moved higher. When the bronchial artery coursing into the middle lobe bronchus was preserved, the blood flow in the bronchus was preserved at 82.8%±1.3%. When the branches of the bronchial arteries running both inside and outside of the intermediate bronchial trunk were cut at high positions, regional oxygen saturation level decreased to 55.7%±1.2%. CONCLUSIONS: The preservation of at least one bronchial artery at the level of the middle lobe bronchus minimizes the reduction of tissue oxygen saturation at the lower lobe bronchial stump. The ligation of bronchial arteries at a higher position results in desaturation <60%, which may increase the risk of bronchial stump fistula.

The accuracy of cone-beam computed tomography and augmented fluoroscopy-guided bronchoscopic marking of multiple small-sized pulmonary nodules in a hybrid operating room: a retrospective cohort study.

BACKGROUND: For the minimally invasive excision of small-sized pulmonary nodules, bronchoscopic markings are increasingly being performed owing to advancements in video-assisted thoracic surgery (VATS). Hybrid operating room equipment is utilized for bronchoscopic VATS markings. We aimed to compare the marking accuracy between bronchoscopic VATS and other marking techniques such as computed tomography-guided percutaneous marking and conventional X-ray fluoroscopy-guided bronchoscopic marking. METHODS: Patients with small-sized pulmonary nodules scheduled to undergo VATS were enrolled in the study. A mixture of 50 to 100 µL of diluted indocyanine green and iopamidol was injected adjacent to the pulmonary nodules as a VATS marker. Patients receiving each of the three image-guided techniques were categorized into group A (computed tomography-guided percutaneous injection), group B (X-ray fluoroscopy-guided virtual bronchoscopy-assisted bronchoscope injection), and group C (cone-beam computed tomography and augmented fluoroscopy-guided virtual bronchoscope-assisted bronchoscopic injection in the hybrid operating room). VATS marking accuracy and procedural complications were compared among the three groups. RESULTS: In total, 61 patients with 73 pulmonary nodules were eligible for analysis. VATS marking was successful for 15/16 nodules in group A, 28/30 nodules in group B, and 25/27 nodules in group C. Marking accuracy was 5.75±4.59, 15.00±14.02, and 6.05±6.11 (mm), respectively. Multiple markings were successful in 0/1 (0%), 5/6 (83.3%), and 5/5 (100.0%) nodules in groups A, B, and C, respectively. A small pneumothorax occurred in 3/15 (20.0%) patients in group A. CONCLUSIONS: The cone-beam computed tomography and augmented fluoroscopy-guided bronchoscopic approach performed in a hybrid operating room is accurate and equivalent to the computed tomography-guided percutaneous approach, and it enables the VATS marking of multiple pulmonary nodules without causing a secondary pneumothorax.

Fluorescence visualization of the intersegmental plane by bronchoscopic instillation of indocyanine green into the targeted segmental bronchus: determination of the optimal settings.

OBJECTIVE: To determine the appropriate amount of indocyanine green for bronchial insufflation. METHODS: We enrolled 20 consecutive patients scheduled for anatomical segmentectomy in the Kochi Medical School Hospital. After inducing general anesthesia, 6 to 60 mL of 200-fold-diluted indocyanine green (0.0125 mg/mL) was insufflated into the subsegmental bronchi in the targeted pulmonary segmental bronchus. The volume of the targeted pulmonary segments was calculated using preoperative computed tomography. Fluorescence spread in the segmental alveoli was visualized using a dedicated near-infrared thoracoscope. RESULTS: The targeted segment was uniformly visualized by indocyanine green fluorescence in 16/20 (80.0%) cases after insufflating indocyanine green. A receiver operating characteristic curve indicated that the area under the curve was 0.984; the optimal cut-off volume of diluted indocyanine green for insufflation was 8.91% of the calculated targeted pulmonary segment volume. CONCLUSIONS: The setting for indocyanine green insufflation was optimized for near-infrared fluorescence image-guided anatomical segmentectomy. By injecting the correct amount of indocyanine green, fluorescence-guided anatomical segmentation may be performed more appropriately.

Preoperative AminoIndex Cancer Screening (AICS) abnormalities predict postoperative recurrence in patients undergoing curative resection for non-small cell lung cancer.

BACKGROUND: AminoIndex™ Cancer Screening (AICS (lung)) was developed as a screening test for lung cancer using a multivariate analysis of plasma-free amino acid (PFAA) profiles. According to the developed index composed of PFAA, the probability of lung cancer was categorized into AICS (lung) ranks A, B, and C in order of increasing risk. The aim of the present study was to investigate the relationship between the preoperative AICS (lung) rank and surgical outcomes in patients who underwent curative resection for non-small cell lung cancer (NSCLC). METHODS: Preoperative blood samples were collected from 297 patients who underwent curative resection for NSCLC between 2006 and 2015. PFAA concentrations were measured. The relationship between the preoperative AICS (lung) rank and clinicopathological factors was examined. The effects of the preoperative AICS (lung) rank on postoperative outcomes were also analyzed. RESULTS: The AICS (lung) rank was A in 93 patients (31.3%), B in 82 (27.6%), and C in 122 (41.1%). The AICS (lung) rank did not correlate with any clinicopathological factors, except for age. Based on follow-up data (median follow-up period of 6 years), postoperative recurrence was observed in 22 rank A patients (23.7%), 15 rank B (18.3%) and 49 rank C (40.2%). In the univariate analysis, preoperative AICS (lung) rank C was a worse factor of recurrence-free survival (p = 0.0002). The multivariate analysis identified preoperative AICS (lung) rank C (HR: 2.17, p = 0.0005) as a significant predictor of postoperative recurrence, particularly in patients with early-stage disease or adenocarcinoma. CONCLUSION: Preoperative AICS (lung) rank C is a high-risk predictor of postoperative recurrence in patients undergoing curative resection for NSCLC.

A Hyperactive RelA/p65-Hexokinase 2 Signaling Axis Drives Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is an isolated type of lymphoma of the central nervous system and has a dismal prognosis despite intensive chemotherapy. Recent genomic analyses have identified highly recurrent mutations of MYD88 and CD79B in immunocompetent PCNSL, whereas LMP1 activation is commonly observed in Epstein-Barr virus (EBV)-positive PCNSL. However, a lack of clinically representative preclinical models has hampered our understanding of the pathogenic mechanisms by which genetic aberrations drive PCNSL disease phenotypes. Here, we establish a panel of 12 orthotopic, patient-derived xenograft (PDX) models from both immunocompetent and EBV-positive PCNSL and secondary CNSL biopsy specimens. PDXs faithfully retained their phenotypic, metabolic, and genetic features, with 100% concordance of MYD88 and CD79B mutations present in PCNSL in immunocompetent patients. These models revealed a convergent functional dependency upon a deregulated RelA/p65-hexokinase 2 signaling axis, codriven by either mutated MYD88/CD79B or LMP1 with Pin1 overactivation in immunocompetent PCNSL and EBV-positive PCNSL, respectively. Notably, distinct molecular alterations used by immunocompetent and EBV-positive PCNSL converged to deregulate RelA/p65 expression and to drive glycolysis, which is critical for intracerebral tumor progression and FDG-PET imaging characteristics. Genetic and pharmacologic inhibition of this key signaling axis potently suppressed PCNSL growth in vitro and in vivo. These patient-derived models offer a platform for predicting clinical chemotherapeutics efficacy and provide critical insights into PCNSL pathogenic mechanisms, accelerating therapeutic discovery for this aggressive disease. SIGNIFICANCE: A set of clinically relevant CNSL xenografts identifies a hyperactive RelA/p65-hexokinase 2 signaling axis as a driver of progression and potential therapeutic target for treatment and provides a foundational preclinical platform. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5330/F1.large.jpg.

Incision Edge "Lifting Method" in Cerebral Bypass Surgery: A Novel Optional Technique for Narrow or Thin Recipient Arteries.

BACKGROUND: Cerebral bypass surgery, such as the superficial temporal artery-middle cerebral artery bypass, is one of the essential procedures for cerebral revascularization. However, very narrow or thin blood vessels will increase the risk of anastomotic problems, such as occurs in Moyamoya disease. For such vessels, we have devised a "lifting method" in the recipient arteriotomy. In the present study, we have introduced this novel optional technique and evaluated its effects. METHODS: The lifting method is a procedure of lifting the incision edge of a linear incision on the recipient vessel to widen the ostium. We attempted the lifting method in 23 consecutive patients (41 arteries) and, as a historical control, compared the results with those from the conventional method in 25 consecutive patients (37 arteries) for the previous 3 years. We compared patient age, years of surgical experience, recipient vessel diameter, anastomotic events, and final patency. As a subanalysis, the same evaluations were performed separately for patients with Moyamoya disease. Furthermore, the time required for the lifting procedure was measured retrospectively. RESULTS: The incidence of anastomotic events with the conventional method was 13.5% overall and 19% in those with Moyamoya disease. No adverse events occurred with the lifting method (P < 0.05). No statistically significant differences were found for the other factors, including final patency between the 2 groups. The time required for the lifting procedure averaged 1 minute, 15 seconds. CONCLUSIONS: Use of the lifting method widens and secures the ostium in a recipient vessel and greatly facilitates operability. We have found it to be a foolproof method enabling safe and reliable anastomosis even with narrow or thin vessels.

Near-infrared fluorescent solid material for visualizing indwelling devices implanted for medical use.

BACKGROUND: In clinical practice, various devices are implanted into the body for medical reasons. As X-ray fluoroscopy is necessary to visualize medical devices implanted into the body, the development of a less-invasive visualization method is highly desired. This study aimed to investigate the clinical applicability of our novel solid material that emits near-infrared fluorescence. METHODS: We developed a solid resin material that emits near-infrared fluorescence. This material incorporates a near-infrared fluorescent pigment, with quantum yield ≥ 20 times than that of indocyanine green. It can be sterilized for medical treatment. This resin material is designed to be molded into a catheter and inserted into the body with an endoscope clip. In this preclinical experiment using a swine model, the resin material was embedded into the body of the swine and visualized with a near-infrared fluorescence camera system. RESULTS: Endoscopic clips were placed in the mucosa of the stomach, esophagus, and large intestine, and the indwelling ureteral catheters were successfully visualized by near-infrared fluorescence laparoscopy. CONCLUSIONS: We confirmed the tissue permeability of the fluorescence emitted by our novel near-infrared fluorescent material and the possibility of its clinical application. This material may allow visualization of devices embedded in the body.

Thiel's embalming method with additional intra-cerebral ventricular formalin injection (TEIF) for cadaver training of head and brain surgery.

Thiel's embalming method provides natural coloration, flexibility, and tissue plasticity, and is used widely to prepare specimens for cadaver surgical training. However, this method causes brain softening, thereby restricting the cadaver surgical training of intra-cranial procedures. In this study, three cadavers were embalmed using formalin fixation, Thiel's embalming method, and Thiel's embalming method with additional intra-cerebral ventricular formalin injection, respectively. We also established rat models of the three embalming methods to develop and determine the best method for retaining adequate brain elasticity. The intra-ventricular formalin injection in the cadaver was performed through the Kocher's point, as in the classical external ventricular drain procedure. Both, the cadaver brains and rat models yielded consistent shear wave measurements and brain surface stiffness data. Notably, the Thiel's embalming method with additional intra-cerebral ventricular formalin injection yielded suitable elasticity for brain cadaver surgical training in terms of brain mobilization and surgical field deployment, and also discharged formaldehyde in undetectable quantities. To our knowledge, this is the first report in which a fixed quality, namely, brain elasticity for the performance of head and brain cadaver surgical training, has been evaluated in a cadaver subjected to the Thiel's embalming method with immersion fixation in the cerebrospinal fluid space. We conclude that the Thiel's embalming method with additional intra-cerebral ventricular formalin injection can maintain the brain elasticity, and may therefore improve the quality of head and brain cadaver surgical training safely and easily.

Suprasellar Benign Chondroma: A Case Report and Literature Review.

Intracranial chondroma is a rare benign tumor comprising only 0.2% of all intracranial tumors. A 27-year-old woman presented with visual dysfunction and headache. Brain computed tomography and magnetic resonance imaging revealed a suprasellar mass lesion with a calcified component. Gross total removal was achieved via a basal interhemispheric approach. Postoperatively, visual function improved to the normal range, and no recurrence was evident 4 years later. Histopathological examination confirmed the diagnosis of benign chondroma. Preoperative differentiation of chondromas from chordomas is clinically important, because of the different treatment and prognostic implications. The only effective treatment for chondroma is total surgical removal. We present a case of gross total resection of a suprasellar chondroma with reference to the literature.

In-vitro proliferation assay with recycled ascitic cancer cells in malignant pleural mesothelioma: A case report.

BACKGROUND: We report the first case, to the best of our knowledge, of massive ascites due to recurrent malignant pleural mesothelioma that was controlled using KM-cell-free and concentrated ascites reinfusion therapy (KM-CART). The tumor cells derived via KM-CART were utilized secondarily in an in vitro cell growth assay using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) to investigate anticancer drug susceptibility. CASE SUMMARY: A 56-year-old man presented with recurrent malignant mesothelioma with massive ascites; more than 4000 mL of ascitic fluid was removed, filtered, and concentrated using KM-CART, and the cell-free ascitic fluid was reinfused into the patient to improve quality of life. Cancer cells isolated secondarily in an in vitro proliferation assay using CD-DST exhibited low sensitivity to pemetrexed and high sensitivity to gemcitabine. Treatment with gemcitabine maintained stable disease for 4 mo. CONCLUSION: The combination of KM-CART and CD-DST may be a promising treatment option for malignant ascites associated with malignant mesothelioma.

Human recombinant erythropoietin improves motor function in rats with spinal cord compression-induced cervical myelopathy.

OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.