Idiopathic Primary Necrotizing Fasciitis of the Breast: A Case Report

Necrotizing fasciitis (NF) is a life-threatening infection characterized by extensive necrosis and inflammation of subcutaneous tissue and the fascia. Only a few cases of NF in the breast have been reported, and imaging findings of primary breast NF have not been described in the literature. As primary NF in the breast is extremely rare, it can be misdiagnosed as an abscess or cellulitis, and its diagnosis may be delayed. However, early diagnosis is crucial because delays can lead to fatal sepsis or requirement for total mastectomy. Herein, the authors report a rare case of primary breast NF that was diagnosed early using enhanced breast CT and successfully managed with local debridement. CT revealed a large cystic mass with an air-fluid level, a thickened deep fascia without remarkable enhancement, and extensive subcutaneous emphysema with subcutaneous fat infiltrations in the right breast.

Can We Skip Intraoperative Evaluation of Sentinel Lymph Nodes? Nomogram Predicting Involvement of Three or More Axillary Lymph Nodes before Breast Cancer Surgery / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The American College of Surgeons Oncology Group Z0011 trial reported that complete dissection of axillary lymph nodes (ALNs) may not be warranted in women with clinical T1-T2 tumors and one or two involved ALNs who were undergoing lumpectomy plus radiation followed by systemic therapy. The present study was conducted to identify preoperative imaging predictors of ≥ 3 ALNs. MATERIALS AND METHODS: The training set consisted of 1,917 patients with clinical T1-T2 and node negative invasive breast cancer. Factors associated with ≥ 3 involved ALNs were evaluated by logistic regression analysis. The validation set consisted of 378 independent patients. The nomogram was applied prospectively to 512 patients who met the Z0011 criteria. RESULTS: Of the 1,917 patients, 204 (10.6%) had ≥ 3 positive nodes. Multivariate analysis showed that involvement of ≥ 3 nodes was significantly associated with ultrasonographic and chest computed tomography findings of suspicious ALNs (p < 0.001 each). These two imaging criteria, plus patient age, were used to develop a nomogram calculating the probability of involvement of ≥ 3 ALNs. The areas under the receiver operating characteristic curve of the nomogram were 0.852 (95% confidence interval [CI], 0.820 to 0.883) for the training set and 0.896 (95% CI, 0.836 to 0.957) for the validation set. Prospective application of the nomogram showed that 60 of 512 patients (11.7%) had scores above the cut-off. Application of the nomogram reduced operation time and cost, with a very low re-operation rate (1.6%). CONCLUSION: Patients likely to have ≥ 3 positive ALNs could be identified by preoperative imaging. The nomogram was helpful in selective intraoperative examination of sentinel lymph nodes.

Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. MATERIALS AND METHODS: We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to < or = 3 cm was assessed. Nomograms were built and validated in an independent cohort. RESULTS: BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to < or = 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size < or = 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor < or = 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. CONCLUSION: We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

Predictive Significance of p53, Ki-67, and Bcl-2 Expression for Pathologic Complete Response after Neoadjuvant Chemotherapy for Triple-Negative Breast Cancer / 한국유방암학회지

PURPOSE: Patients with triple-negative breast cancer (TNBC) with pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) have superior survival outcomes compared to those with residual disease after NAC. This study investigated the value of three biomarkers, p53, Ki-67, and Bcl-2 for predicting pCR in NAC-treated patients with TNBC. METHODS: Between 2003 and 2012, 198 patients with pathologically confirmed primary TNBC were treated with two different taxane-based chemotherapeutic regimens prior to surgery. Before NAC, expression of p53 (cutoff 25%), Ki-67 (cutoff 10%), and Bcl-2 (cutoff 10%) was assessed immunohistochemically in core biopsy specimens. The incidence of pCR was correlated with the expression of these biomarkers. RESULTS: Overall, pCR occurred in 37 of the 198 patients (18.7%). A significant association was observed between the pCR rate and overexpression of the p53 and Ki-67 biomarkers. Multivariate analysis showed that only p53 expression was independently associated with pCR to NAC (odds ratio, 3.961; p=0.003). The sensitivity, specificity, positive predictive value, and negative predictive value of p53 expression for predicting pCR were 77.8%, 50.3%, 26.2%, and 90.9%, respectively. The pCR rate was the lowest (5.2%) in patients with low expression of both p53 and Ki-67, and it was the highest (25.8%) when both biomarkers showed high expression. CONCLUSION: Expression of p53 was significantly associated with pCR after NAC in patients with TNBC, suggesting that this biomarker might be particularly valuable in identifying TNBC patients prone to have residual disease after NAC.

Low Rates of Additional Cancer Detection by Magnetic Resonance Imaging in Newly Diagnosed Breast Cancer Patients Who Undergo Preoperative Mammography and Ultrasonography / 한국유방암학회지

PURPOSE: We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography. METHODS: We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified. RESULTS: Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci. CONCLUSION: Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.

Reliability of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients / 한국유방암학회지

PURPOSE: Sentinel lymph node biopsy (SLNB) is an accurate and effective means of axillary nodal staging in early breast cancer. However its indication after neoadjuvant chemotherapy (NAC) is under constant debate. The present study evaluates the reliability of SLNB in assessing axillary nodal status after NAC. METHODS: Data from 281 patients who had received NAC and subsequent SLNB were reviewed. The identification and false negative rates of SLNB were determined and the clinicopathologic factors associated with false negative results were investigated using univariate analysis. RESULTS: The identification rate of SLNB after NAC was 93.6% and the false negative rate was 10.4%. Hormone receptor status, especially progesterone receptor positivity, was significantly associated with false negative results. The accuracy of intraoperative frozen section examination of sentinel lymph nodes was 91.2%. CONCLUSION: The identification rate of SLNB and the accuracy of intraoperative frozen section examination after NAC are comparable to the results without NAC in patients with early breast cancer. However considering the high false negative rates, general application of SLNB after NAC should be avoided. Patients with progesterone-positive tumors and non-triple-negative breast cancers may be a select group of patients in whom SLNB can be employed safely after NAC, but further studies are necessary.

Validation of a Scoring System for Predicting Malignancy in Patients Diagnosed with Atypical Ductal Hyperplasia Using an Ultrasound-Guided Core Needle Biopsy / 한국유방암학회지

PURPOSE: The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. METHODS: The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. RESULTS: The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size >15 mm and a patient age of > or =50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p<0.001; area under the curve, 0.852). No patient with a U score <3.5 had an underestimated lesion. CONCLUSION: The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of < or =3.5 indicates that surgical excision may not be necessary.

One-step Nucleic Acid Amplification (OSNA): Intraoperative Rapid Molecular Diagnostic Method for the Detection of Sentinel Lymph Node Metastases in Breast Cancer Patients in Korean Cohort / 한국유방암학회지

PURPOSE: Sentinel lymph node (SLN) biopsy has become a standard procedure in breast cancer patient management. Accurate intraoperative assessment of metastasis of SLNs is essential for appropriate selection to avoid unnecessary axillary dissection. The aim of this study was to evaluate the performance of one-step nucleic acid amplification (OSNA) assay for detection of sentinel lymph node metastasis examination in breast cancer patients. METHODS: In this study, we compared intraoperative OSNA to histological investigation with multi-level observation in 284 sentinel lymph nodes of 199 patients. Surgically obtained sentinel lymph nodes were sectioned into 2 mm intervals of up to four pieces, half of which were examined with the OSNA assay. The other half of adjacent pieces were histopathologically examined both intraoperatively and postoperatively. The presence/absence of metastases was judged by observing hematoxylin and eosin staining and cytokeratin (AE1/ AE3) immunohistochemically stained multiple slides from one lymph node. RESULTS: Among 199 patients included, 36 cases were positive on histological examination and 34 cases were positive on OSNA assay. There were 14 discordant cases. The overall concordance with histology was 93.0% (95% confidence interval [CI], 0.86-0.96), with a sensitivity of 77.8% (95% CI, 0.61-0.90), specificity of 96.3% (95% CI, 0.92-0.99), positive predictive value of 82.4% (95% CI, 0.65-0.93) and negative predictive value of 95.2% (95% CI, 0.91-0.98). The kappa statistic analysis indicated substantial agreement of both methods, with a value of 0.76 (95% CI, 0.64-0.88). The average turnaround time was 39.0 minutes. CONCLUSION: The results of this study indicate that the OSNA assay has equivalent accuracy to histopathology in detecting breast cancer metastasis to lymph nodes when each method is assigned two alternate blocks of four blocks sectioned at 2 mm intervals.

Clinicopathological Characteristics and Factors Affecting Recurrence of Ductal Carcinoma In Situ in Korean Women / 한국유방암학회지

PURPOSE: As breast cancer screening becomes more popular in Korea, incidence of ductal carcinoma in situ (DCIS) of breast has increased to more than 10% of all breast cancer diagnosed. We aimed to show the clinicopathological characteristics and factors affecting recurrence of DCIS in Korean women. METHODS: We retrospectively reviewed 152 DCIS patients who underwent breast conserving surgery in Seoul National University Hospital between January 1995 and December 2005. RESULTS: Mean age at diagnosis was 46.7 years (24 to 66 years). Mean follow up duration of the patients was 73.82 months (0.80 to 168.43 months). Recurrence of disease occurred in 19 (12.5%) patients: 2 in contralateral breast, 15 in ipsilateral breast, and 2 in axilla. One patient showed ipsilateral breast recur after excision of axillary metastasis. Eight (42.11%) of all recurrence was infiltrating ductal carcinoma and one of them showed bone metastasis during follow up. In an multivariate analysis of factors affecting recurrence, younger age at diagnosis and omission of radiotherapy had significant association with recurrence (p=0.005 and p=0.002, respectively). However, tumor size (p=0.862), microinvasion (p=0.988), histologic grade (p=0.157), estrogen receptor status (p=0.401) and resection margin status (p=0.112) were not significantly correlated with recurrence. There was no breast cancer associated mortality. CONCLUSION: In this study, we found that the younger age at diagnosis and omission of adjuvant radiotherapy are independent predictors of recurrence in Korean DCIS patients.

Efficacy of Breast Ultrasonography for Detection of Local, Regional, and Contralateral Recurrence of Breast Cancer / 한국유방암학회지

PURPOSE: Breast ultrasonography (US) is not recommended for recurrence monitoring after breast cancer surgery due to the lack of evidence for its advantage. The purpose of this study was to evaluate the usefulness of US for detecting local recurrence (LR), regional recurrence (RR) and contralateral breast cancer (CBC) in breast cancer patients during follow-up. METHODS: The medical records of 5,833 breast cancer patients who underwent breast cancer surgery between January 2003 and December 2009 were reviewed retrospectively. Physical examination (PE), mammography (MMG), and US were done routinely to detect recurrences. Detection rate for locoregional and contralateral recurrence was compared between the three modalities. RESULTS: During the follow-up period, 125 LR, 46 RR, 83 CBC, and 29 synchronous local and regional recurrences developed in 245 patients among the study population of 5,833 breast cancer patients. Median time to recurrence was 34.7 months. The recurrence detection rate was 51.9%, 43.5%, and 90.1% for PE, MMG, and US, respectively. Mean size of the recurrent lesions detected by US (1.57 cm) was smaller than that of PE (2.69 cm) and MMG (2.03 cm) (p=0.002). CONCLUSION: Breast US had higher recurrence detection rate for LR, RR, and CBC than PE or MMG after breast cancer surgery.

The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer / 한국유방암학회지

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.

The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer / 한국유방암학회지

PURPOSE: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients. METHODS: We reviewed the records of the stage IV breast cancer patients who were treated at Seoul University Hospital between April 1992 and December 2007. The tumor and clinical characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients. RESULTS: Of the 198 identified patients, 110 (55.8%) received surgical excision of their primary tumor and 88 (44.2%) did not. The mean survival was 67 months vs. 42 months for the surgically treated patients vs. the patients without surgery, respectively (p=0.0287). On a multivariate analysis with using the Cox model and after adjusting for the estrogen receptor status, visceral metastases, the number of metastatic sites and trastuzumab treatment, surgery was an independent factor for improved survival (hazard ratio, 0.55; 95% confidence interval, 0.31-0.97; p=0.041). CONCLUSION: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival. Randomized prospective trials are needed to firmly recommend surgical resection of the primary tumor in stage IV breast cancer patients.

The Effects of Soybean Diet on the Diabetic Neuropathy in the Rats / 대한해부학회지

Neuropathy is a serious and disabling complication that contributes to increased morbidity and mortality in diabetic patients. There is progressive distal to proximal axonal atrophy that ultimately leads to Wallerian degeneration. This study was performed to identify the effect of soy bean on diabetic neuropathy using morphometry. Male Sprague-Dawley rats were grouped into control, diabetic with red chow diet and diabetic with soy bean diet. The myelinated nerve fibers were counted and fiber size distributions were evaluated in each group at 4 and 8 weeks, respectively. Diabetic neuropathy didn't develop in streptozotocin-induced diabetic rats at four weeks. At 8 weeks, the myelinated nerve fiber in diabetic with soy bean diet was larger in number than that in diabetic to which did not be administered insulin. The number of myelinated nerve fiber was not different between diabetic group with insulin and without insulin. Mean myelinated nerve fiber size was smaller in diabetic with soy bean diet than diabetic with red chow diet and control. Histogram of fiber size distribution was shifted to left in diabetic with red chow and soy bean diet groups compared to control. Light and electron microscopic findings showed marked degeneration of nerve fibers in diabetic with red chow diet but preservation in diabetic with soy bean diet. The level of glucose and HbA1c was lower in diabetic with soy bean diet than red chow diet. Soy bean could be effective in the protection of neuropathy induced by diabetes mellitus.

Correlation between C-MYC and HER2 Amplification in Non-selected Breast Cancers / 한국유방암학회지

PURPOSE: c-myc and HER2 have been reported be amplified in 20% to 30% of clinical breast cancers and appears to be related with poor clinical outcome. The relationship between amplification of c-myc and HER2 and other clinical and biological characteristics of the breast cancers, including clinical outcome, are described. METHODS: c-myc and HER2 amplification were analyzed on 225 consecutive non-selected breast cancers by fluorescence in situ hybridization using tissue microarray technology. RESULTS: c-myc was amplified in 33 cases (15.4%) and HER2 was amplified in 49 cases (23.3%). c-myc amplification was significantly increased with HER2 amplification (p<0.001) and closely linked with cell proliferative activity measured by Ki67 labeling index (p=0.010). In univariate survival analysis, lymph node status, tumor size, and histologic grade of the tumors were significant prognostic factors. However, lymph node status was the only significant prognostic factor for predicting patient survival in multivariate analysis. Patient survival was not different according to c-myc amplification status and c-myc amplification showed no significant correlation with clinco-pathologic parameters of the tumors. CONCLUSION: A strong correlation between c-myc and HER2 amplifications, and cell proliferative activity indicate a biologic link between c-myc and HER2 in breast cancer.

The Effect of Ependymal Cell Transplantation on Nerve Regeneration after Spinal Cord Injury in Rats / 대한해부학회지

Nerve regeneration in the central nervous system has been studied by grafting various tissues and cells. Choroid plexus epithelial cells represent a continuation of ventricular ependymal cells and have the same origin as regarded as modified ependymal cells. To study the use of choroid plexus ependymal cell grafting for nerve regeneration in the spinal cord, the choroid plexus was excised from the lateral and fourth ventricles of adult Sprague-Dawley rats, minced into small fragments, and grafted at the T9 level in adult rat spinal cord transected or contused. In this study, transplants of choroid plexus ependymal cells were successfully used to promote functional and structural recovery after spinal cord transection and contusion. The area of damaged spinal cord was diminished after choroid plexus ependymal cells transplantation. Nearly normal anterior horn cells were observed immediately distal to the transected region. Tyrosine hydroxylase immunoreactive descending fibers were observed in the distal region beyond transected area. These findings indicate that choroid plexus ependymal cells have the ability to facilitate axonal growth, suggesting that they may be a promising candidate as graft for the promotion of nerve regeneration in the spinal cord.

Microscopic Changes of the Spinal Cord after the Intrathecal Administration of Ondansetron in the Rat / 대한마취과학회지

BACKGROUND: Serotonin type 3 receptors are abundant in the dorsal horn of the spinal cord and in the spinal tract of the trigeminal nerve in the medulla. Moreover, the intrathecal (IT) or epidural administration of ondansetron, a selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, might prevent postoperative nausea, vomiting and intrathecal opioid-induced pruritus more effectively than the drug administered systemically. Before new drugs for spinal administration are accepted for clinical practice, experimental neurotoxicity studies must be undertaken. This study was performed in rats in order to reveal the behavioral and morphological signs of spinal cord damage after chronic IT ondansetron administration. METHODS: Rats were anesthetized using enflurane in oxygen and an 8 cm polyethylene catheter was advanced caudally through the atlanto-occipital membrane under aseptic surgical conditions. Twelve rats were randomly divided into two groups, an ondansetron (O) group (n = 6) and a normal saline (N) group (n = 6). After postoperative 7 days, we started the IT injection of ondansetron 40microgram (20microliter) or normal saline 20microliter once a day over two weeks. Potential changes of spinal cords were evaluated morphologically by light microscopy (LM) and electron microscopy (EM) in addition to behavioral changes. RESULTS: No rat in either groups showed any motor or behavioral changes during the administration of ondansetron. By LM and EM, all six rats in the O group showed massive neovascularization over the white and gray matters of spinal cords. CONCLUSIONS: The results suggest that chronic IT administration of ondansetron causes pathologic changes in the rat spinal cord.

The Effect of Capsaicin on the Sensory Nerve of the Rat Prostate / 대한해부학회지

Prostatodynia is a common and chronic debilitating disease manifested by pain referable to the prostate such as perineal, inguinal, lower back, and suprapubic pain. It has been estimated that more than half of all men suffer from this entity sometime in their lives. Although infection, autoimmunity, and intraprostatic reflux are some of the candidates for its cause, the etiology and pathogenesis of prostatodynia remains unclear. This study investigated the effect of capsaicin, a selective nociception blocking agent, on the prostatic afferent, and determined the presence of capsaicin sensitive nerve fiber at the rat prostate. Adult male Sprague-Dawley rats were used for the experiment. Capsaicin (4mM) or vehicle (10% ethanol, 10% Tween 80, 80% normal saline) 0.125 ml each was injected directly into the right ventral prostate and sacrificed at 1, 2, 24 hours, 1 week and 1 month after injection. Five rats were sacrificed at each time interval. Calcitonin gene related peptide (CGRP) and neurofilament (NF) immunohistochemistry was performed at the L2 dorsal root ganglion (DRG). CGRP and substance P (SP) immunohistochemistry was performed at L2 and T8 dorsal horn, and the prostate. The change in the number of c-fos positive cells was determined at L2, L6, and T8 dorsal horn. Change in c-fos positive cells was also compared between those injected with xylene only and those injected with xylene 24 hours and 1 week after capsaicin pretreatment. The prostate was observed under hematoxylin-eosin (H-E) staining for histological change after capsaicin injection. The number of CGRP positive cells decreased nearly half at the L2 DRG 24 hours after capsaicin injection and remained decreased up until 1 month. However, the number of NF positive cells did not change suggesting the effect of capsaicin only on B-type neurons. Decrease in CGRP and SP at the dorsal horn was observed only at L2 after capsaicin injection. There was no change at T8 and after vehicle injection. The number of c-fos positive cells after capsaicin and vehicle injection reached a peak at 2 hours at L2 and at 2 and 1 hour, respectively, at L6. However, c-fos positive cell was not observed at T8 even after capsaicin injection. In animals pretreated with capsaicin, injection of xylene induced fewer c-fos positive cells at both L2 and L6 compared to animals injected with xylene only. H-E staining of the prostate did not reveal any significant histological change of the prostate after capsaicin injection. However, CGRP and SP positive nerve fibers was not observed 1 week after capsaicin treatment. Direct injection of capsaicin into the rat prostate induced depletion of CGRP and SP, neurotransmitters related to pain conduction, at the DRG, dorsal horn and prostate suggesting that the prostatic afferent is affected by capsaicin. The decreased c-fos positive cells observed after capsaicin pretreatment further supports this observation and demonstrates that capsaicin injection can desensitize nociception originating from the rat prostate.

Morphometric Study of the Effects of Various Analgesic Compound in Experimental Arthritis Model / 대한해부학회지

Arthritis is the most common disease of joint in old age and almost all the old human are suffering from arthritis. Arthritis gives so severe pain hard to endure that it can devastate human. But we still do not know where the arthritic pain comes from and the generation mechanism of it. For the study of effects of anti-inflammatory drugs on the c-fos immunoreactive neurons, substance P-and CGRPimmunoreactive neurons in dorsal horn and DRG, cyclooxygenase (COX) inhibitors indomethacin (0.5 mg/kg), piroxicam (0.5 mg/kg), NMDA receptor antagonist MK 801 (2 mg/kg), and capsaicin (50 mg/kg) were administered to the experimental arthritis model. Male Sprague-Dawley rats were used for this study. Arthritis was induced by injection of 4% kaolin followed by 2% carrageenan into the articular capsule of left knee. Two hours, 24 hours and 7 days after injection, animals were sacrificed and processed for imunohistochemical staining for c-fos in spinal dorsal horn, for substance P (SP) and CGRP in DRG. The results were as follows; 1. The number of c-fos immunoreactive neurons were significantly decreased at 2 h after piroxicam and MK-801 administration and 1 week after indomethacin, MK-801 and capsaicin treatment in the inflamed side of dorsal horn. 2. There were the significant decrease of SP-and CGRP-immunoreactive area 2 h after indomethacin administration and 1week after capsaicin treatment in the inflamed side of dorsal horn. 3. The number of SP- and CGRP-immunoreactive neurons in DRG were decreased after drugs administration and no difference is in the degree of effectiveness between drugs. Indomethacin and piroxicam which is an inhibitors of COX, significantly reduced the expression of c-fos proteins and desensitized nociceptive primary afferents at the early time, and capsaicin, a pungent algesic substance, decreased the level of c-fos protein, SP and CGRP over a wider time in dorsal horn and DRG.

Studies on the changes of c-fos protein in spinal cord and neurotransmitter in dorsal root ganglion of the rat with an experimental peripheral neuropathy

Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.

The Morphological Studies on the Effects of Nerve Growth Factor on the Schwann Cell in the Diabetic Neuropathy in the Rats / 대한해부학회지

Diabetic neuropathy is a broad term that encompasses many destructive syndromes that various kinds of neuronal population is affected in diabetes mellitus. Diabetic neuropathy has been postulated to occur by diverse pathogenetic mechanisms. Recent studies suggest that the reduction of neurotrophic factors is one of the causes of diabetic neuropathy. This study was performed to identify the effect of nerve growth factor on Schwann cell in the streptozotocin-induced diabetic rats morphologically. Sprague-Dawley rats (weighed about 200 gm) were rendered diabetes by injection of streptozotocin (STZ 65 mg/kg) and nerve growth factor was administered for 4 weeks. The result obtained are as followed: 1. Degenerations in cytoplasmic organelles of Schwann cell of the myelinated nerve fibers in diabetic rats were identified. 2. Degenerations in cytoplasmic organelles of the Schwann cell of the unmyelinated nerve fibers in diabetic rats were identified and abnormal axons were appeared. 3. Nerve growth factor had an effect on the recovery of degeneration and it was more effective in myelinated nerve fibers. These results suggest that early administration of nerve growth factor have the effect of protection of diabetic neuropathy by morphological study.