Development of a Deep Learning Model for the Analysis of Dorsal Root Ganglion Chromatolysis in Rat Spinal Stenosis.

Objective: To create a deep learning (DL) model that can accurately detect and classify three distinct types of rat dorsal root ganglion neurons: normal, segmental chromatolysis, and central chromatolysis. The DL model has the potential to improve the efficiency and precision of neuron classification in research related to spinal injuries and diseases. Methods: H&E slide images were divided into an internal training set (80%) and a test set (20%). The training dataset was labeled by two pathologists using pre-defined grades. Using this dataset, a two-component DL model was developed with the first component being a convolutional neural network (CNN) that was trained to detect the region of interest (ROI) and the second component being another CNN used for classification. Results: A total of 240 lumbar dorsal root ganglion (DRG) pathology slide images from rats were analyzed. The internal testing results showed an accuracy of 93.13%, and the external dataset testing demonstrated an accuracy of 93.44%. Conclusion: The DL model demonstrated a level of agreement comparable to that of pathologists in detecting and classifying normal and segmental chromatolysis neurons, although its agreement was slightly lower for central chromatolysis neurons. Significance: DL in improving the accuracy and efficiency of pathological analysis suggests that it may have a role in enhancing medical decision-making.

Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis.

BACKGROUND: We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). METHODS: This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. RESULTS: A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. CONCLUSIONS: Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Therapeutic effect of epidural hyaluronic acid in a rat model of foraminal stenosis.

PURPOSE: Since receiving a warning from the US Food and Drug Administration (FDA) about injection of corticosteroids into the epidural space having serious adverse events, we have sought alternative medications for injection at this site. Hyaluronic acid (HA) has anti-adhesive, anti-inflammatory, and lubricating properties, so could potentially be useful for spinal pain. The exact mechanism by which spinal stenosis develops is not fully understood, but is likely to involve inflammation. Therefore, we hypothesized that HA could have a therapeutic effect in spinal stenosis. This study evaluated the effects of epidural administration of HA on alleviation of pain in a rat model of foraminal stenosis. MATERIALS AND METHODS: After creating the animal model, HA (HA group) or saline solution (S group) was administered via an epidural catheter. The paw-withdrawal threshold to mechanical stimulation and motor dysfunction were monitored for up to 21 days. Tissue was collected to evaluate the degree of adhesion, inflammation in the perineural area, and chromatolysis in the dorsal root ganglion (DRG). RESULTS: The mechanical withdrawal threshold was restored in the HA group but not in the S group (P < 0.001). The HA group also showed less fibrosis (P = 0.026) and less chromatolysis (P = 0.002) than the S group. CONCLUSION: HA administered epidurally had a therapeutic effect on the allodynia and hyperalgesia induced by chronic compression of the DRG.

Effect of Hypercholesterolemia on Fatty Infiltration and Quality of Tendon-to-Bone Healing in a Rabbit Model of a Chronic Rotator Cuff Tear: Electrophysiological, Biomechanical, and Histological Analyses.

BACKGROUND: The incidence of healing failure after rotator cuff repair is high, and fatty infiltration is a crucial factor in healing failure. PURPOSE: To verify the effect of hypercholesterolemia on fatty infiltration and the quality of tendon-to-bone healing and its reversibility by lowering the cholesterol level in a chronic tear model using the rabbit supraspinatus. STUDY DESIGN: Controlled laboratory study. METHODS: Forty-eight rabbits were randomly allocated into 4 groups (n = 12 each). After 4 weeks of a high-cholesterol diet (groups A and B) and a regular diet (groups C and D), the supraspinatus tendon was detached and left alone for 6 weeks and then was repaired in a transosseous manner (groups A, B, and C). Group D served as a control. Group A continued to receive the high-cholesterol diet until the final evaluation (6 weeks after repair); however, at the time of repair, group B was changed to a general diet with administration of a cholesterol-lowering agent (simvastatin). Histological evaluation of the fat-to-muscle proportion was performed twice, at the time of repair and the final evaluation, and an electromyographic (EMG) test, mechanical test, and histological test of tendon-to-bone healing were performed at the final evaluation. RESULTS: For the EMG test, group A showed a significantly smaller area of compound muscle action potential compared with groups C and D (all P <.01), and group B showed a larger area than group A, almost up to the level of group C (P = .312). Similarly, group A showed significantly lower mechanical properties both in load-to-failure and stiffness compared with groups C and D (all P <.05). In addition, although not significantly different, the mechanical properties of group B were higher than those of group A (mean load-to-failure: group A = 42.01 N, group B = 58.23 N [P = .103]; mean stiffness: group A = 36.32 N/mm, group B = 47.22 N/mm [P = .153]). For the histological test, groups A and B showed a significantly higher fat-to-muscle proportion than did groups C and D at 6 weeks after detachment (all P <.05), but at the final evaluation, group B showed a decreased fat-to-muscle proportion (mean ± SD: from 64.02% ± 11.87% to 54.68% ± 10.47%; P = .146) compared with group A, which showed increased fat-to-muscle proportion (from 59.26% ± 17.80% to 78.23% ± 10.87%; P = .015). Groups B and C showed better tendon-to-bone interface structures than did group A, which showed coarse and poorly organized collagen fibers with fat interposition. CONCLUSION: Hypercholesterolemia had a deleterious effect on fatty infiltration and the quality of tendon-to-bone repair site, and lowering hypercholesterolemia seemed to halt or reverse these harmful effects in this experimental model. CLINICAL RELEVANCE: Systemic diseases such as hypercholesterolemia should be tightly controlled during the perioperative period of rotator cuff repair.

Therapeutic effect of epidurally administered lipo-prostaglandin e1 agonist in a rat spinal stenosis model.

BACKGROUND: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. METHODS: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 µg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. RESULTS: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. CONCLUSIONS: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

A retrieval thrombectomy technique with the Solitaire stent in a large cerebral artery occlusion.

BACKGROUND: To describe preliminary experiences and the procedural details of retrieval thrombectomy using a self-expanding and fully retrievable Solitaire stent (ev 3 Inc., CA, USA) in acute ischemic stroke (AIS) patients with large artery occlusions. METHODS: Eight patients with AIS were treated by mechanical thrombectomy using a self-expanding, fully retrievable stent (Solitaire, ev 3 Inc., CA, USA). The stent was deployed to cover the whole intra-arterial clot and then it was slowly retrieved while occluding the internal cerebral artery (ICA) with a balloon guiding catheter. Additionally, continuous negative pressure was applied through the balloon guiding catheter with a specially designed gun device. Occlusion sites were M1 in six cases including one combined supraclinoid ICA occlusion and the other combined M2 occlusion, M2 in 1 case and one basilar artery top. RESULTS: Complete recanalization was achieved in all patients. Procedure time was 45 min or less in seven cases and 70 min in one case. Distal emboli occurred in one case in which the balloon guide catheter was not used. Only in this case was intraarterial fibrinolytics infusion necessary. There was no post-operative intracranial hemorrhage. CONCLUSIONS: In our experience, retrieval thrombectomy with the Solitaire stent was a simple and effective method for reopening large cerebral arteries in AIS patients.

Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53.

We investigated pseudoprogression (psPD) in patients with malignant gliomas treated with radiotherapy (RT) and maintenance temozolomide (TMZ) in terms of incidence, outcomes, and predictive and prognostic factors. We evaluated p53 overexpression by immunohistochemical analysis of thirty-five tumor samples as a predictor for psPD. The time to progression and overall survival were compared between subgroups, psPD versus early progression (ePD) versus nonprogression (nonPD). Eight patients developed psPD among eighteen patients with lesion enlargement at the first MRI scan, and the others were classified as ePD. The remaining stable or improved patients were classified as nonPD. All patients with psPD were alive at last follow-up (median follow-up period was 12 months; range 5.8-58.5 months). Overall survival of psPD patients was significantly higher than ePD patients (P < 0.01). There was no significant survival difference between the psPD group and nonPD group (P = 0.25). Seven (87.5%) of eight tumors with psPD showed p53 overexpression, as compared to 3 (30%) of the ten tumors with ePD (P = 0.03). Our study indicates that psPD following chemoradiotherapy with TMZ is associated with significantly better overall survival compared to that of ePD, and is comparable to nonPD group. Overexpression of p53 was identified as a potential biomarker for predicting the development of psPD.

Should transition zone biopsies be added to 12-core systematic biopsies of the prostate?

PURPOSE: To investigate the value of additional transition zone (TZ) biopsies following 12-core biopsies in the detection and staging of prostate cancer. METHODS: From October 2006 to March 2007, 199 transrectal sonographic (TRUS)-guided prostate biopsies (group 1) in 12 peripheral zones (PZ) were performed. Another 199 consecutive patients (group 2) underwent two TZ biopsies in addition to twelve PZ biopsies from March 2007 to July 2007. Mean prostate-specific antigen (PSA) level, prostate volume, Gleason score, and cancer detection rate of each group were compared. The anatomic distribution of prostate cancer in group 2 was also analyzed. RESULTS: Prostate cancer was detected in 76 of 199 patients (38.2%) in group 1 and 71 out of 199 patients (35.3%) in group 2. The cancer detection rate, mean PSA level, prostate volume, and Gleason score were not statistically different in the 2 groups. Cancer was detected by additional TZ biopsies alone in just one out of 71 patients (1.4%). CONCLUSION: Routine TZ biopsies following 12-core systematic biopsies are not warranted for the detection of TZ cancer because of their low additional yield.

Merosin-deficient congenital muscular dystrophy in Korea.

Congenital muscular dystrophy (CMD) is a clinically and genetically heterogeneous group of muscle disorders, presenting at birth or early infancy with hypotonia, muscle weakness, joint contractures, and dystrophic changes in the muscles. Merosin-deficient CMD (MDCMD) is rare in Asian populations, but more common in Caucasians, comprising about 50% of CMDs. We report, for the first time in Korea, eight patients with merosin-deficient CMD, confirmed by immunohistochemical staining of muscle or skin samples. We also describe their wide spectrum of clinical features and neuroimaging findings. Among 35 patients diagnosed as CMD, almost 23% of them were proved to have MDCMD with typical phenotypic presentation. We infer that prevalence of MDCMD in Korea may not be as low as expected. One of the patients was diagnosed by skin biopsy, which is good alternative for diagnosis of MDCMD.

Degos' disease (malignant atrophic papulosis) as a fatal cause of acute abdomen: report of a case.

Degos' disease, otherwise known as "malignant atrophic papulosis," is a rare condition characterized by typical cutaneous lesions. Its involvement of the gastrointestinal (GI) tract is usually associated with a poor prognosis. We report a case of Degos' disease with GI involvement, which ultimately caused peritonitis, sepsis, and death, despite all treatment measures. A 59-year old woman was admitted to our hospital with acute generalized abdominal pain. The patient had presented initially with multiple skin lesions 2 years earlier, and even with surgery for small-bowel perforation 10 months before this admission, Degos' disease had not been diagnosed. Explorative laparotomy revealed multifocal, ischemic changes in the small bowel with perforation in the mid-jejunum. After the operation, she suffered recurrent small-bowel fistulas and died within 3 months. In a patient with acute abdominal pain and typical atrophic papules, clinicians should retain a high index of suspicion for Degos' disease with GI involvement, even though it is rare.

Preoperative MR imaging in the evaluation of seminal vesicle invasion in prostate cancer: pattern analysis of seminal vesicle lesions.

PURPOSE: To develop an image-based classification system for seminal vesicle lesions (SVL) to detect seminal vesicle invasion (SVI) in prostate cancer and to evaluate whether pattern analysis of SVL with MR imaging could improve the accuracy of evaluating SVI. MATERIALS AND METHODS: The MR images of 217 patients who had undergone retropubic radical prostatectomy (RRP) due to prostate cancer were retrospectively analyzed by two uroradiologists, focusing on SVL. The SVL on T2-weighted sequences was classified as five classes. In each class the results were correlated with histopathologic findings. RESULTS: Fourteen (6.5%) of 217 patients had evidence of SVI at histopathologic evaluation after RRP. Pattern analysis of SVL showed 71.4% sensitivity, 96.6% specificity for predicting SVI. ROC curves for the subjective scoring of SVI showed that reader 1 had an area under the curve (AUC) of 0.69 and reader 2 had an AUC of 0.81. The overall accuracy of pattern analysis was superior to both serum prostate-specific antigen (PSA) level and subjective scoring (P < 0.01, McNemar test). CONCLUSION: The classification system of SVL on the basis of their imaged morphologic features can provide an objective standard and simplify the abnormal findings to help predict SVI in prostate cancer. Pattern analysis of SVL with MR imaging improves the accuracy of detecting SVI.

Prediction of pathological stages before prostatectomy in prostate cancer patients: analysis of 12 systematic prostate needle biopsy specimens.

OBJECTIVE: To identify the most reliable predictor of the pathological stage among multiple parameters obtained by performing systematic biopsies and to assess the predictive value of any identified parameters in combination with the prostate specific antigen and the Gleason scores. METHODS: We examined 5 biopsy parameters from 12 systematic needle biopsy results in 104 consecutive prostate cancer patients who underwent prostatectomy: the number of cores positive for cancer, percentage of positive biopsy cores, total linear cancer length (absolute sum of tumor length at each core), percentage cancer length (total cancer length divided by total length of cores obtained x100), and maximum cancer core length. The predictive values of these parameters were assessed using multivariate logistic analysis and receiver operating characteristic analysis. We evaluated whether the most reliable biopsy parameter in combination with traditional variables show better predictability of the pathological stage than traditional variables alone by receiver operating characteristic analysis. RESULTS: Of 104 patients, 85 (82.9%) had organ confined cancer and 19 (17.1%) showed extraprostatic extension. Of the five parameters examined, maximum cancer length was found to best predict pathological staging. Although insignificant, adding results of maximum cancer length to prostate specific antigen and Gleason scores improved predictability. Of 41 patients with a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and Gleason score of <7, none showed extraprostatic extension. CONCLUSIONS: The maximum cancer length was found to be the most reliable predictor of disease staging. The findings of a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and a Gleason score of <7 can suggest an organ-confined disease.

Surgical outcome and prognostic factors of pediatric epilepsy caused by cortical dysplasia.

OBJECTS: We analyzed 30 patients with cortical dysplasia (CD) and epilepsy to evaluate the clinical characteristics and surgical outcome of both epilepsy control and neurocognition. MATERIALS AND METHODS: The mean ages at seizure onset and at the time of the operation were 3.6 years (range, 1 month-12.6 years) and 10.3 years (range, 1.5-18.3 years), respectively. The mean follow-up period was 3.2 years (range, 1-5.3 years). (18)FDG-positron emission tomography was the most sensitive and magnetic resonance imaging was the most specific in localizing the lesion. Developmental/intellectual delay was predominant in the early-onset group (n=18, seizure onset <3 years), with intelligence tending to be normal in the late-onset group (n=12, seizure onset >or=3 years). Mild CD predominated in the late-onset epilepsy group and moderate or severe CD in the early-onset group (p=0.005). The surgical success rate of epilepsy control was 87%. A better outcome was obtained if the lesion was confined to the temporal lobe. School performance was favorable in 43%. The age at seizure onset and preoperative developmental/intellectual delay were the important prognostic factors in school performance as well as the epilepsy control. A total of 77% of patients had relatively good social adaptation. Successful epilepsy control and good school performance were affirmative conditions precedent to social adaptation. CONCLUSIONS: Due to the favorable control of epilepsy and its effect on school performance and social adaptation, surgical treatment is strongly recommended for cortical dysplasia and intractable epilepsy.