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Ewing sarcoma and peripheral primitive neuroectodermal tumor (ES/pPNET) is an undifferentiated malignant tumor that is most prevalent in children and young adults and often radiologically mimics a meningioma. A 38-year-old female patient visited our hospital with complaints of right-sided tinnitus, right hemiparesis, and imbalance. She underwent preoperative imaging and was subsequently diagnosed as having a meningioma on the petrous ridge. After partial resection, EWSR1-FLI1 gene fusion was confirmed, and she was diagnosed with ES/pPNET. The tumor was successfully treated using a multidisciplinary approach of adjuvant chemo- and radiotherapy. This case is noteworthy because it is an extremely rare case of an intracranial ES/pPNET, and it is worth sharing our clinical experience that the tumor was successfully treated through a multidisciplinary therapeutic approach even though complete resection was not achieved.
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Purpose@#The KNOG-1101 study showed improved 2-year PFS with temozolomide during and after radiotherapy compared to radiotherapy alone for patients with anaplastic gliomas. This trial investigates the effect of concurrent and adjuvant temozolomide on health-related quality of life (HRQoL). @*Materials and Methods@#In this randomized, open-label, phase II trial, 90 patients with World Health Organization grade III glioma were enrolled across multiple centers in South Korea between March 2012 to February 2015 and followed up through 2017. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) and 20-item EORTC QLQ-Brain Neoplasm (QLQ-BN20) were used to compare HRQoL between patients assigned to concurrent chemoradiotherapy with temozolomide followed by 6 cycles of adjuvant temozolomide (arm A) and radiotherapy (RT) alone (arm B). @*Results@#Of the 90 patients in the study, 84 patients (93.3%) completed the baseline HRQoL questionnaire. Emotional functioning, fatigue, nausea and vomiting, dyspnea, constipation, appetite loss, diarrhea, seizures, itchy skin, drowsiness, hair loss, and bladder control were not affected by the addition of temozolomide. All other items did not differ significantly between arm A and arm B throughout treatment. Global health status particularly stayed consistent at the end of adjuvant temozolomide (p=0.47) and at the end of RT (p=0.33). @*Conclusion@#The addition of concurrent and adjuvant temozolomide did not show negative influence on HRQoL with improvement of progression-free survival for patients with anaplastic gliomas. The absence of systematic and clinically relevant changes in HRQoL suggests that an overall long-term net clinical benefit exists for concurrent and adjuvant temozolomide.
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Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.
ABSTRACT
Programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibition has revolutionized the treatment paradigm of urothelial carcinoma (UC). Several PD-L1 assays are conducted to formulate appropriate treatment decisions for PD-1/PD-L1 target therapy in UC. However, each assay has its own specific requirement of antibody clones, staining platforms, scoring algorithms, and cutoffs for the determination of PD-L1 status. These prove to be challenging constraints to pathology laboratories and pathologists. Thus, the present article comprehensively demonstrates the scoring algorithm used and differences observed in each assay (22C3, SP142, and SP263). Interestingly, the SP142 score algorithm considers only immune cells and not tumor cells (TCs). It remains controversial whether SP142 expressed only in TCs truly accounts for a negative PD-L1 case. Moreover, the scoring algorithm of each assay is complex and divergent, which can result in inter-observer heterogeneity. In this regard, the development of artificial intelligence for providing assistance to pathologists in obtaining more accurate and objective results has been actively researched. To facilitate efficiency of PD-L1 testing, several previous studies attempted to integrate and harmonize each assay in UC. The performance comparison of the various PD-L1 assays demonstrated in previous studies was encouraging, the exceptional concordance rate reported between 22C3 and SP263. Although these two assays may be used interchangeably, a clinically validated algorithm for each agent must be applied.
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A 23-year-old Korean woman with a residence history in Kenya and Malawi for about 2 years presented with gross hematuria for 1 month. Blood tests were within normal range except eosinophilia. Asymmetrically diffuse wall thickening and calcification were observed at the urinary bladder on CT. Multiple erythematous nodular lesions were observed in the cystoscopy and transurethral resection was done. Numerous eggs of Schistosoma haematobium with granulomatous inflammation were observed in the submucosal layer of the bladder. The patient was diagnosed with schistosomiasis-related cystitis and treated with praziquantel (40 mg/kg/day) twice before and after transurethral resection. This case suggests that S. haematobium infection should be considered as a cause of hematuria in Korea when the patient had a history of traveling endemic areas of schistosomiasis.
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Purpose@#We investigated the efficacy of temozolomide during and after radiotherapy in Korean adultswith anaplastic gliomas without 1p/19q co-deletion. @*Materials and Methods@#This was a randomized, open-label, phase 2 study and notably the first multicenter trial forKorean grade III glioma patients. Eligible patients were aged 18 years or older and hadnewly diagnosed non-co-deleted anaplastic glioma with an Eastern Cooperative OncologyGroup performance status of 0-2. Patients were randomized 1:1 to receive radiotherapyalone (60 Gy in 30 fractions of 2 Gy) (control group, n=44) or to receive radiotherapy withconcurrent temozolomide (75 mg/m2/day) followed by adjuvant temozolomide (150-200mg/m2/day for 5 days during six 28-day cycles) (treatment group, n=40). The primary endpointwas 2-year progression-free survival (PFS). Seventy patients (83.3%) were availablefor the analysis of the isocitrate dehydrogenase 1 gene (IDH1) mutation status. @*Results@#The two-year PFS was 42.2% in the treatment group and 37.2% in the control group. Overallsurvival (OS) did not reach to significant difference between the groups. In multivariableanalysis, age was a significant risk factor for PFS (hazard ratio [HR], 2.08; 95% confidenceinterval [CI], 1.04 to 4.16). The IDH1mutation was the only significant prognostic factor forPFS (HR, 0.28; 95% CI, 0.13 to 0.59) and OS (HR, 0.19; 95% CI, 0.07 to 0.50). Adverseevents over grade 3 were seen in 16 patients (40.0%) in the treatment group and werereversible. @*Conclusion@#Concurrent and adjuvant temozolomide in Korean adults with newly diagnosed nonco-deleted anaplastic gliomas showed improved 2-year PFS. The survival benefit of this regimenneeds further analysis with long-term follow-up at least more than 10 years.
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Background@#High-grade glioma (HGG) with primary leptomeningeal seeding (PLS) at initial diagnosis is rare. The purpose of this study was to identify its clinical features and to describe the clinical treatment outcomes. @*Methods@#We retrospectively reviewed the medical records of patients with HGG (World Health Organization grade III or IV) at our institution between 2004 and 2019, and patients with PLS at the initial diagnosis were enrolled in the study. Clinical features, such as the location of leptomeningeal seeding, surgical methods, and degree of resection, were sorted based on electronic medical records also containing performance scale, and hematological and serological evaluations. Radiological findings and immunohistochemical categories were confirmed. Furthermore, we sought to determine whether controlling intracranial pressure (ICP) via early cerebrospinal fluid (CSF) diversion increases overall survival (OS) after the initial diagnosis. @*Results@#Of the 469 patients with HGG in our institution, less than 2% had PLS at the initial diagnosis. Most patients suffered from headache, diplopia, and dizziness. Pathological findings included 7 glioblastomas and 2 anaplastic astrocytomas. Seven of the 9 patients underwent CSF diversion. All patients were administered concurrent chemoradiotherapy (CCRT) with temozolomide, 89% of which started adjuvant temozolomide and 33% of which completed the six cycles of adjuvant temozolomide.The OS of patients with HGG and PLS was 8.7 months (range, 4-37), an extremely poor result compared to that of other studies. Also, the 1-year and 2-year OS rates were 44.4% and 16.7%, respectively. @*Conclusion@#Diagnosis and treatment of HGG with PLS are challenging. Aggressive control of ICP followed by early initiation of standard CCRT seems to be helpful in improving symptoms. However, despite aggressive treatment, the prognosis is poor. A multicenter trial and research may be necessary to create a standardized protocol for this disease.
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BACKGROUND: The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas. METHODS: A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis. RESULTS: According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDHmut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDHmut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDHmut, 11 diffuse astrocytoma, IDHwt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDHmut, eight anaplastic astrocytoma, IDHwt, NOS; and 35 glioblastoma, IDHwt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDHmut and 1p/19q co-deleted and diffuse astrocytoma IDHmut showed significantly higher survival than those with diffuse astrocytoma IDHwt, NOS (p<.01). CONCLUSIONS: Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.
Subject(s)
Humans , Astrocytoma , Brain , Central Nervous System , Chromosome Deletion , Classification , Diagnosis , Fluorescence , Glioblastoma , Glioma , Global Health , Immunohistochemistry , In Situ Hybridization , Isocitrate Dehydrogenase , Nervous System Neoplasms , Nervous System , Oligodendroglioma , World Health OrganizationABSTRACT
This report presents a case of fourth ventricle neurenteric cyst (NE cyst) mimicking hemangioblastoma, which developed in a 50-year-old woman. A tiny enhancing mural portion of the fourth ventricle in MRI suggested that the cyst was hemangioblastoma, but pathological evidence showed that the cyst was in fact NE cyst in the fourth ventricle. In order to make proper decision on to what extent of surgical resection should be done, considering every possibility in differential diagnosis might be helpful. This case reports an unusual pathology in 4th ventricle, considering the patient's age, and demonstrates that a rarer disease may share radiological features of a common disease.
Subject(s)
Female , Humans , Middle Aged , Diagnosis, Differential , Fourth Ventricle , Hemangioblastoma , Magnetic Resonance Imaging , Neural Tube Defects , PathologyABSTRACT
PURPOSE: The purpose of this study was to analyze the detection rate of prostate cancers from targeted biopsy specimens of midline focal lesions and to investigate the ultrasonographic findings to reduce unnecessary additional targeted biopsies. METHODS: Ninety-eight men with midline focal lesions detected on transrectal ultrasonography were enrolled. Additional targeted biopsies for midline focal lesions were performed after 12-core random systematic biopsies. Correlations between the ultrasonographic characteristics of midline focal lesions and the pathologic results were analyzed. RESULTS: Twenty of 98 targeted biopsy cores (20.4%) were positive for malignancy. In a univariate analysis, midline focal lesions without bulging contours (P=0.023), with involved margins (P=0.001), without hypoechoic perilesional rims (P=0.005), and with longer diameters (P=0.005) were statistically significant for cancer detection. In a multivariate analysis, involved margin (P=0.027), having longer diameter (P=0.011) or absence of hypoechoic perilesional rim (P=0.025) made a statistically significant contribution to cancer detection. CONCLUSION: Biopsy of midline focal lesions was not always non-significant in the detection of prostate cancer. Additional targeted biopsies should be considered in cases of midline focal lesions with involved margins but without hypoechoic perilesional rims.
Subject(s)
Humans , Male , Biopsy , Image-Guided Biopsy , Multivariate Analysis , Prostate , Prostatic Neoplasms , UltrasonographyABSTRACT
In recent years there has been significant growth in multidisciplinary cancer treatment. In cancer patient management, multidisciplinary cancer treatment is essential for evaluation of treatment response and proper decision making. Multidisciplinary cancer treatment has some systematic problems in Korea; however, it is expected to be increasingly activated in tertiary medical institutions. Pathologists are core members of multidisciplinary cancer treatment teams. We reviewed the pathologist's role in multidisciplinary cancer treatment. The days of precision medicine have arrived with remarkable development in molecular pathology. Pathologists not only histologically confirm the cancer diagnosis and pathologic stage but also evaluate both prognostic factors and predictive factors determining targeted therapy. Pathologists' participation in multidisciplinary cancer treatment and explanation of pathologic results can draw good curative effect and improve patient satisfaction. The only caveat is that pathologists need to be brought down to the patient's level while describing pathologic findings. We suspect that pathologists' role will expand as pathologists participate in multidisciplinary cancer treatment in the era of precision medicine.
Subject(s)
Humans , Decision Making , Diagnosis , Korea , Pathology, Molecular , Patient SatisfactionABSTRACT
BACKGROUND: The aim of this study was to determine the regional heterogeneity and clinicopathological significance of microRNA-21 (miR-21) in advanced colorectal cancer (CRC) patients with distant metastasis. METHODS: miR-21 expression was investigated by using locked nucleic acid- fluorescence in situ hybridization in the center and periphery of the primary cancer and in distant metastasis from 170 patients with advanced CRC. In addition, α-smooth muscle actin and desmin were evaluated to identify cancer-associated fibroblasts (CAFs) by using immunohistochemistry. RESULTS: The miR-21 signal was observed in the cancer stroma. The expression of miR-21 (a score of 1-4) in the center and periphery of the primary cancer and in distant metastasis was observed in specimens from 133 (78.2%), 105 (61.8%), and 91 (53.5%) patients, respectively. miR-21 expression was heterogeneous in advanced CRC. Discordance between miR-21 expression in the center of the primary cancer and either the periphery of the primary cancer or distant metastasis was 31.7% or 44.7%, respectively. miR-21 stromal expression in the periphery of the primary cancer was significantly associated with a better prognosis (p=.004). miR-21 expression was significantly associated with CAFs in the center of the primary cancer (p=.001) and distant metastases (p=.041). CONCLUSIONS: miR-21 expression is observed in cancer stroma related to the CAF quantity and frequently presents regional heterogeneity in CRC. Our findings indicate that the role of miR-21 in predicting prognosis may be controversial but provide a new perspective of miR-21 level measurement in cancer specimens.
Subject(s)
Humans , Actins , Colorectal Neoplasms , Desmin , Fibroblasts , Fluorescence , Genetic Heterogeneity , Immunohistochemistry , In Situ Hybridization , Neoplasm Metastasis , Population Characteristics , PrognosisABSTRACT
Extra ventricular neurocytoma (EVN) is a rare brain tumor with histologic features similar with a central neurocytoma, but located outside of the ventricular system. In this study, we present an unusual case of hypothalamic EVN in a 14-year-old patient. The patient underwent subtotal removal and had tumor relapse. The patient was then treated using intensity modulated radiation therapy, and the tumor remained stable for 24 months. This case report may be important in that this is the first pediatric case of EVN located in the hypothalamic region. EVN has similar radiologic features with pilocytic astrocytomas and therefore a hypothalamic EVN may be misdiagnosed as a hypothalamic glioma. Also, the pathologic-radiologic-clinical correlation of EVN located in the hypothalamic area may be different from that of EVNs originating from other usual sites.
Subject(s)
Adolescent , Humans , Astrocytoma , Brain Neoplasms , Glioma , Hypothalamic Neoplasms , Neurocytoma , Radiotherapy, Adjuvant , RecurrenceABSTRACT
Extra ventricular neurocytoma (EVN) is a rare brain tumor with histologic features similar with a central neurocytoma, but located outside of the ventricular system. In this study, we present an unusual case of hypothalamic EVN in a 14-year-old patient. The patient underwent subtotal removal and had tumor relapse. The patient was then treated using intensity modulated radiation therapy, and the tumor remained stable for 24 months. This case report may be important in that this is the first pediatric case of EVN located in the hypothalamic region. EVN has similar radiologic features with pilocytic astrocytomas and therefore a hypothalamic EVN may be misdiagnosed as a hypothalamic glioma. Also, the pathologic-radiologic-clinical correlation of EVN located in the hypothalamic area may be different from that of EVNs originating from other usual sites.
Subject(s)
Adolescent , Humans , Astrocytoma , Brain Neoplasms , Glioma , Hypothalamic Neoplasms , Neurocytoma , Radiotherapy, Adjuvant , RecurrenceABSTRACT
BACKGROUND: Meningiomas show high recurrence rates even after curative tumor removal. The invasiveness of meningiomas may contribute to their high recurrence rates. Recently, c-MET and hepatocyte growth factor (HGF) have been reported to be involved in cancer invasion. METHODS: We examined the immunohistochemical expression of c-MET and HGF in 100 cases of patients with meningiomas who have undergone complete tumor removal. RESULTS: c-MET(-High) and HGF(-High) were found in 17% and 13% of meningiomas, respectively. Brain invasion was observed in 17.6% of c-MET(-High) meningiomas, but in only 2.4% of c-MET(-Low) meningiomas (p=.033). Bone/soft tissue invasion was observed in 23.5% of c-MET(-High) meningiomas and in 9.6% of c-MET(-Low) meningiomas (p=.119). HGF(-High) did not show statistical association with brain invasion or bone/soft tissue invasion. c-MET(-High) demonstrated shorter recurrence-free survival (RFS, 93.5+/-8.2 months vs 96.1+/-1.9 months); however, this difference was not statistically significant (p=.139). There was no association of HGF(-High) with RFS. CONCLUSIONS: This study demonstrates that c-MET(-High) is associated with brain invasion of meningiomas, and that c-MET expression may be a useful predictive marker for meningioma recurrence. Patients with invasive meningiomas with high expressions of c-MET may be good candidates for targeted therapy using c-MET inhibitors.
Subject(s)
Humans , Brain , Hepatocyte Growth Factor , Immunohistochemistry , Meningioma , Neoplasm Invasiveness , Proto-Oncogene Proteins c-met , RecurrenceABSTRACT
BACKGROUND: Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification. METHODS: We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases. RESULTS: According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs. CONCLUSIONS: We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.
Subject(s)
Humans , Antibodies , Astrocytoma , Classification , Coloring Agents , Genes, erbB-1 , Genes, p53 , Glioblastoma , Immunohistochemistry , Isocitrate Dehydrogenase , ErbB ReceptorsABSTRACT
BACKGROUND/AIMS: Intestinal metaplasia (IM) is a premalignant condition. This study aimed to evaluate the correlation between endoscopic and histological findings of IM. METHODS: The cases of IM were graded by conventional endoscopy, and biopsies were taken from the antrum and body of 1,333 subjects for histological IM diagnosis. Multivariate analyses were performed to identify the factors that affect the sensitivity of endoscopic IM diagnosis. RESULTS: The sensitivity/specificity of endoscopic IM diagnosis based on histology was 24.0%/91.9% for the antrum and 24.2%/88.0% for the body. As indicated by multivariate analysis, the presence of endoscopic atrophic gastritis (AG) (odds ratio [OR], 4.73; 95% confidence interval [CI], 2.07 to 10.79) and the activity of mucosal inflammation (OR, 2.21; 95% CI, 1.08 to 4.54) were associated with the sensitivity of endoscopic IM diagnosis in the antrum, while the presence of endoscopic AG (OR, 8.02; 95% CI, 4.55 to 14.15), dysplasia (OR, 2.40; 95% CI, 1.07 to 5.39), and benign gastric ulcers (OR, 0.35; 95% CI, 0.15 to 0.081) were associated with the sensitivity of endoscopic IM diagnosis in the body. CONCLUSIONS: As the sensitivity of endoscopic IM diagnosis was low, a high index of suspicion for IM is necessary in the presence of atrophy, and confirmation by histology is also necessary.
Subject(s)
Atrophy , Biopsy , Endoscopy , Gastritis, Atrophic , Inflammation , Metaplasia , Multivariate Analysis , Stomach UlcerABSTRACT
Giant cell arteritis (GCA) is a rare disease among Asians. Arteritic anterior ischemic optic neuropathy, which accompanies GCA, has not yet been reported in Koreans. Diagnosis of GCA is difficult if typical symptoms other than visual loss are absent. Here, we report a case of an 83-year-old Korean woman presenting with sudden visual loss in both eyes (oculus uterque, OU). Her visual acuities included perception of light in the right eye (oculus dexter, OD) and perception of hand motion in the left eye (oculus sinister, OS). The results of the Hardy-Rand-Rittler test and Ishihara test showed total dyschromatopsia OU. The Goldmann perimetry test revealed a total field defect OD and paracentral island OS. Fundus examination revealed chalky-white disc swelling OU. Other systemic symptoms and signs were unremarkable. The erythrocyte sedimentation rate, C-reactive protein and platelet count were highly elevated. Temporal artery biopsy revealed multiple lymphocytes and multinucleated giant cells in the arterial media layer. To our knowledge, this is the first report of GCA in a Korean that has been confirmed with temporal artery biopsy. In conclusion, silent GCA can occur in Koreans, and hence, elderly patients presenting with chalky-white disc swelling, and corresponding laboratory findings must be evaluated for GCA.
Subject(s)
Aged, 80 and over , Female , Humans , Asian People , Giant Cell Arteritis/complications , Optic Neuropathy, Ischemic/diagnosis , Vision Disorders/diagnosisABSTRACT
BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.
Subject(s)
Animals , Rats , Administration, Oral , Calcium Channels , gamma-Aminobutyric Acid , Ganglia, Spinal , Horns , Inflammation , Injections, Epidural , Neuritis , Neurons , Spinal Cord , PregabalinABSTRACT
BACKGROUND: Although chemotherapy-related hepatic injury has been reported in colorectal cancer liver metastasis (CRLM) patients, the morphologic changes caused by chemotherapeutic agents and the effect of chemotherapy on postoperative outcome remain ill-defined. A comprehensive review of the morphologic changes in the post-chemotherapy non-neoplastic liver was performed and the clinical effect of preoperative chemotherapy in CRLM patients was analyzed. METHODS: Hematoxylin-eosin, Masson's trichrome and reticulin-stained slides from non-neoplastic livers obtained from 89 CRLM patients were analyzed, and the clinicopathologic features were correlated with the status of chemotherapy exposure. RESULTS: Histopathologic features of sinusoidal injury (sinusoidal dilatation, centrilobular perivenular fibrosis, parenchymal extinction lesions, small vessel obliteration, and hepatocyte plate disruption) were significantly more frequent in oxaliplatin-exposed livers (p<0.05). The extent of sinusoidal dilatation was positively correlated with increasing numbers of chemotherapy cycles (p=0.022). Abnormal preoperative liver function tests were more frequently seen (p<0.05) and postoperative total bilirubin was higher in the chemotherapy group (p=0.008). Postoperative morbidity was more common in the chemotherapy group (p=0.044). CONCLUSIONS: Sinusoidal injury is frequently seen in oxaliplatin-treated livers, and its presence, especially when extensive, should be documented in surgical pathology practice. The recognition of sinusoidal injury may provide helpful guidelines for surgeons in deciding the extent of hepatic resection.