Generation of Cortical Brain Organoid with Vascularization by Assembling with Vascular Spheroid

Background and Objectives@#Brain organoids have the potential to improve our understanding of brain development and neurological disease. Despite the importance of brain organoids, the effect of vascularization on brain organoids is largely unknown. The objective of this study is to develop vascularized organoids by assembling vascular spheroids with cerebral organoids. @*Methods@#and Results: In this study, vascularized spheroids were generated from non-adherent microwell culture system of human umbilical vein endothelial cells, human dermal fibroblasts and human umbilical cord blood derived mesenchymal stem cells. These vascular spheroids were used for fusion with iPSCs induced cerebral organoids. Immunostaining studies of vascularized organoids demonstrated well organized vascular structures and reduced apoptosis. We showed that the vascularization in cerebral organoids up-regulated the Wnt/β-catenin signaling. @*Conclusions@#We developed vascularized cerebral organoids through assembly of brain organoids with vascular spheroids. This method could not only provide a model to study human cortical development but also represent an opportunity to explore neurological disease.

Histopathological Analysis of Esophageal Mucosa in Patients with Achalasia

Background/Aims@#Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. @*Methods@#From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. @*Results@#The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. @*Conclusions@#Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.

Histopathological Analysis of Esophageal Mucosa in Patients with Achalasia

Background/Aims@#Achalasia is an esophageal motor disorder that leads to functional esophageal obstruction. Food stasis and bacterial fermentation can predispose an individual to esophageal mucosal inflammation, causing multifocal dysplasia and increasing the risk of developing esophageal squamous cell carcinoma. We aimed to evaluate esophageal mucosal alterations in achalasia patients and determine clinical factors associated with the histopathological findings. @*Methods@#From 2009 to 2013, we obtained endoscopic biopsies from the lower and middle esophagus of 22 patients with achalasia and 17 controls. Patients’ clinical data and histological severity of esophagitis were retrospectively analyzed. Additionally, immunohistochemical staining for CD3, CD20, Ki-67, and p53 was conducted. @*Results@#The median age of achalasia patients was 49.5 years (range, 27 to 82 years), and there were nine males (40.9%). The median symptom duration was 5.8 years (range, 1 to 33.5 years), and 10 patients (45%) underwent previous treatment (nine, balloon dilation; one, botulinum toxin injection). Achalasia patients had significantly more severe esophagitis than did controls (p=0.001, lower esophagus; p=0.008, middle esophagus), and the number of CD3-positive lymphocytes exceeded that of CD20-positive lymphocytes (p<0.001). Achalasia patients also had a higher esophageal Ki-67 proliferation index (p=0.048). Although statistically nonsignificant, p53 expression was only observed in achalasia patients. There was no association between the histological severity of esophagitis and other clinicopathological findings. @*Conclusions@#Achalasia patients showed significantly severe histological esophagitis and a high Ki-67 proliferation index, indicating an increased risk of neoplastic progression. Therefore, careful endoscopic inspection is necessary for the early detection of superficial neoplasia in these patients.

The prognoses and postoperative outcomes of patients with both colorectal cancer and liver cirrhosis based on a nationwide cohort in Korea

Purpose@#The management of patients with colorectal cancer (CRC) who have liver cirrhosis (LC) requires a thorough understanding of both diseases; however, the prognoses and postoperative outcomes of such patients remain understudied. We investigated the effect of LC on surgical and oncologic outcomes in patients with CRC, and identified prognostic factors. @*Methods@#We analyzed 453 patients with CRC and LC (CRC-LC group), 906 with CRC only (CRC group), 906 with LC only (LC group), and 1,812 healthy subjects using health insurance claim data (2008–2013). @*Results@#The CRC-LC group had a higher frequency of intensive care unit admission than the CRC group; there were no differences between the 2 groups in terms of early and late postoperative small bowel obstruction and incisional hernia. However, the 30-day, 60-day, and 90-day mortality rates were all significantly higher in the CRC-LC group. The higher Charlson comorbidity index (hazard ratio [HR], 1.127) and the lower socioeconomic status (HR, 0.985) were significant worse predictors of 5-year survival. Patients with underlying LC had a significantly higher HR in both the advanced CRC (HR, 1.858) and nonadvanced CRC (HR, 1.799) subgroups. However, the nonadvanced CRC subgroup showed a lower HR than the LC group (HR, 0.730). @*Conclusion@#Patients with CRC who had underlying LC had a lower survival rate than did those without LC, although the incidence rates of postoperative complications were not significantly different. The presence of LC was associated with a significantly lower survival rate regardless of CRC presence.

The prognoses and postoperative outcomes of patients with both colorectal cancer and liver cirrhosis based on a nationwide cohort in Korea

Purpose@#The management of patients with colorectal cancer (CRC) who have liver cirrhosis (LC) requires a thorough understanding of both diseases; however, the prognoses and postoperative outcomes of such patients remain understudied. We investigated the effect of LC on surgical and oncologic outcomes in patients with CRC, and identified prognostic factors. @*Methods@#We analyzed 453 patients with CRC and LC (CRC-LC group), 906 with CRC only (CRC group), 906 with LC only (LC group), and 1,812 healthy subjects using health insurance claim data (2008–2013). @*Results@#The CRC-LC group had a higher frequency of intensive care unit admission than the CRC group; there were no differences between the 2 groups in terms of early and late postoperative small bowel obstruction and incisional hernia. However, the 30-day, 60-day, and 90-day mortality rates were all significantly higher in the CRC-LC group. The higher Charlson comorbidity index (hazard ratio [HR], 1.127) and the lower socioeconomic status (HR, 0.985) were significant worse predictors of 5-year survival. Patients with underlying LC had a significantly higher HR in both the advanced CRC (HR, 1.858) and nonadvanced CRC (HR, 1.799) subgroups. However, the nonadvanced CRC subgroup showed a lower HR than the LC group (HR, 0.730). @*Conclusion@#Patients with CRC who had underlying LC had a lower survival rate than did those without LC, although the incidence rates of postoperative complications were not significantly different. The presence of LC was associated with a significantly lower survival rate regardless of CRC presence.

Cancer-Associated Fibroblasts and Desmoplastic Reactions Related to Cancer Invasiveness in Patients With Colorectal Cancer

PURPOSE: We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC). METHODS: Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness. RESULTS: The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding. CONCLUSION: The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.

Primary Glomerulonephritis with Unique C4d Deposition and Concurrent Non-infectious Intermediate Uveitis: a Case Report and Literature Review

C4 glomerulopathy is a recently introduced entity that presents with bright C4d staining and minimal or absent immunoglobulin and C3 staining. We report a case of a 62-year-old man with C4 glomerulonephritis (GN) and uveitis. He presented to the nephrology department with proteinuria and hematuria. The patient also had intermediate uveitis along with proteinuria and hematuria. A kidney biopsy that was performed in light of continuing proteinuria and hematuria showed a focal proliferative, focal sclerotic glomerulopathy pattern on light microscopy, absent staining for immunoglobulin or C3 by immunofluorescence microscopy, with bright staining for C4d on immunohistochemistry, and electron-dense deposits on electron microscopy. Consequently, C4 GN was suggested as the pathologic diagnosis. Although laser microdissection and mass spectrometry for glomerular deposit and pathologic evaluation of the retinal tissue were not performed, this is the first report of C4 GN in Korea and the first case of coexisting C4 GN and uveitis in the English literature.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers. MATERIALS AND METHODS: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray. RESULTS: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor. CONCLUSION: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

Unmasked chronic renal function deterioration after unilateral adrenalectomy in patients with primary aldosteronism

We report 2 cases of chronic estimated glomerular filtration rate (eGFR) decline after unilateral adrenalectomy due to primary aldosteronism. The patients were diagnosed with unilateral adrenal cortical adenoma releasing aldosterone. Two patients were examined for hypertension and hypokalemia. Unilateral laparoscopic adrenalectomy was performed in both cases, and pathology confirmed adrenal cortical adenoma. After adrenalectomy, hypertension and hypokalemia improved to within normal range. However, the eGFR decreased postoperatively, and abdominal computed tomography scan showed decreased kidney size compared to previous images. Kidney biopsy was performed to delineate the exact cause of renal function deterioration and revealed hypertensive changes with chronic interstitial changes, indicating that glomerular hyperfiltration with aldosterone excess masked renal function damage. Physicians have to consider the probability of postadrenalectomy eGFR decline related to chronic hypertensive change.

Establishing Quality Control Ranges for Antimicrobial Susceptibility Testing of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus: A Cornerstone to Develop Reference Strains for Korean Clinical Microbiology Laboratories

Quality control (QC) processes are being performed in the majority of clinical microbiology laboratories to ensure the performance of microbial identification and antimicrobial susceptibility testing by using ATCC strains. To obtain these ATCC strains, some inconveniences are encountered concerning the purchase cost of the strains and the shipping time required. This study was focused on constructing a database of reference strains for QC processes using domestic bacterial strains, concentrating primarily on antimicrobial susceptibility testing. Three strains (Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus) that showed legible results in preliminary testing were selected. The minimal inhibitory concentrations (MICs) and zone diameters (ZDs) of eight antimicrobials for each strain were determined according to the CLSI M23. All resulting MIC and ZD ranges included at least 95% of the data. The ZD QC ranges obtained by using the CLSI method were less than 12 mm, and the MIC QC ranges extended no more than five dilutions. This study is a preliminary attempt to construct a bank of Korean QC strains. With further studies, a positive outcome toward cost and time reduction can be anticipated.

High serum and urine neutrophil gelatinaseassociated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin A nephropathy

BACKGROUND/AIMS: Tubulointerstitial injury plays an important role in the progression of immunoglobulin A nephropathy (IgAN), and neutrophil gelatinase-associated lipocalin (NGAL) is among the most sensitive tubular biomarkers. We investigated whether serum or urine NGAL predicts prognosis in patients with IgAN. METHODS: The present study enrolled patients with biopsy-proven IgAN from January 2005 to December 2010, whose serum and urine samples at the time of kidney biopsy were preserved by freezing. We retrospectively reviewed patient clinical data and followed patients until October 2012. Serum and urine NGAL levels were measured using an enzyme-linked immunosorbent assay kit. Renal progression was defined as an estimated glomerular filtration rate decline by > 50% or progression to end-stage renal disease. RESULTS: There were 121 patients enrolled in this study. During the median follow-up period of 41.49 months, renal progression was found in nine patients (7.4%). Serum or urine NGAL alone could not predict renal progression; however, when serum and urine NGAL levels were combined, belonging to the high NGAL group independently predicted renal progression (hazard ratio [HR], 5.56; 95% confidence interval [CI], 1.42 to 21.73; p = 0.014), along with tubular damage graded according to the Oxford classification as T2 (HR, 8.79; 95% CI, 2.01 to 38.51; p = 0.004). In addition, a Kaplan-Meier curve of renal survival showed significantly higher renal progression in patients in the high NGAL group (log rank, p = 0.004). CONCLUSIONS: In patients with IgAN, high serum and urine NGAL levels at the time of kidney biopsy predict renal progression.

Nodular Fasciitis of the Parotid Gland, Masquerading as Pleomorphic Adenoma

It is difficult to distinguish nodular fasciitis (NF) from other neoplasm of the parotid gland, especially pleomorphic adenoma (PA) by fine needle aspiration cytology. A 39-year-old female noticed a mass in the parotid region. The aspirate material showed cohesive parts composed of the cells that had oval or spindle-shaped nuclei and relatively abundant cytoplasm and some cells with plasmacytoid features. The background substance was fibromyxoid. PA was diagnosed based on the cytologic findings. Subsequently, parotidectomy was performed and NF was diagnosed based on histologic and immunohistochemical findings. NF in the parotid region is rare and may be misdiagnosed as other benign or malignant tumors of the parotid gland. The clinical history of rapid growth and the presence of mitoses and inflammatory cells help to distinguish NF from PA. In addition, immunohistochemical stains for smooth muscle actin and CD68 are useful to confirm the diagnosis of NF.

Mediastinal Thymolipoma with Striated Myoid Cells: Report of a Peculiar Case

No abstract available.

Pathologic Diagnosis of Gastric Intestinal Metaplasia

Gastric intestinal metaplasia (IM) is one of the precursors of gastric adenocarcinoma and is clinically important regarding issue for recommendation of further endoscopic evaluation. Herein we review the histologic characteristics, molecular features and pathological diagnosis of IM. Histologically, IM has been classified as 3 types: type I complete IM, type 2 incomplete IM and type 3 incomplete IM. This classification is important to clinicians as well as pathologists. We emphasize that careful follow up should be recommended in patient with extensive IM or incomplete IM.

A study on dietary habits, health related lifestyle, blood cadmium and lead levels of college students

This study was performed in order to investigate dietary habits, health related lifestyle and blood cadmium and lead levels in female college students. 80 college students (43 males and 37 females) participated in the survey questionnaires. Body weight and height, blood pressure, and body composition were measured. The systolic blood pressure of male and female students were 128.9 +/- 13.9 and 109.8 +/- 12.0, respectively. The diastolic blood pressure of male and female students were 77.1 +/- 10.3 and 66.0 +/- 6.9, respectively, showing that male students had significantly higher blood pressure than female students (P < 0.001). The BMI of male and female students were 23.4 +/- 3.3 and 20.2 +/- 2.3, respectively. Most male students were in the range of being overweight. The dietary habits score of female students was significantly higher than that of male students (P < 0.01).The blood cadmium level of male and female students were 0.54 +/- 0.23 and 0.52 +/- 0.36, respectively. There was no significant difference between male and female students. The blood lead level of male and female students were 1.09 +/- 0.49 and 0.59 +/- 0.45, respectively. The blood lead level of male students was significantly higher than that of female students (P < 0.001). The blood cadmium level of smokers and nonsmokers were 0.69 +/- 0.29 and 0.49 +/- 0.29 respectively (P < 0.05). The blood cadmium level of smokers was significantly higher than that of nonsmokers (P < 0.05). The blood lead level of smokers and nonsmokers were 1.09 +/- 0.43 and 0.80 +/- 0.54, respectively. The blood lead level of smokers was significantly higher than that of nonsmokers (P < 0.05). Therefore, proper nutritional education programs are required for college students in order to improve their dietary and health related living habits.

Ectomesenchymal Chondromyxoid Tumor in the Anterior Tongue: Case Report of a Unique Tumor

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare tumor, exclusively arising in the anterior tongue. Thirty-eight cases have been reported in the English literature. It usually presents as a sessile protrusion and shows round to spindle cells embedded in myxoid to chondroid stroma. Tumor cells are almost always positive for polyclonal glial fibrillary acidic protein (GFAP). We report our experience in the recent treatment of a case of ECMT, the third case in 3 years. The mass in the anterior tongue revealed characteristic morphologic features of ECMT and the expression of polyclonal GFAP. Although ECMT should be differentiated from other mesenchymal tumors including myoepithelioma, its clinical, morphological, and immunohistochemical features enable its diagnosis, especially when pathologists are aware of it.

Cultured human chromaffin cells grafted in spinal subarachnoid space relieves allodynia in a pain rat model / 대한마취과학회지

BACKGROUND: Implantation of xenogenic chromaffin cells into the spinal subarachnoid space can produce analgesia in neuropathic pain models. However, transplantation of xenogeneic chromaffin cell has a potential risk of viral or bacterial infections from animals to humans including encephalopathy due to prion transmission. The aim of this study was to investigate the possibility of developing a homogeneic source of therapeutic chromaffin cells. METHODS: Anti-allodynic effects of human chromaffin cells (HCCs) were evaluated in a neuropathic pain model in rats induced by chronic constriction injury of the sciatic nerve. HCCs encapsulated with alginate-poly-L-lysine-alginate were intrathecally implanted into rats (n = 10), while empty capsules were intrathecally implanted as a control (n = 8). Levels of norepinephrine from encapsulated HCCs before and after nicotinic stimulation were measured. We then perfomed a behavior test (cold allodynia) with acetone. In addition, to assess the potential contribution to pain reduction of opioid peptides released from the HCCs, all animals were injected with naloxone. RESULTS: The concentration of norepinephrine after nicotine stimulation was significantly increased compared to basal levels. Intrathecal implantation of encapsulated HCCs, significantly reduced cold allodynia as compared to rats receiving empty capsules (P < 0.05). Fifteen minutes after the injection of naloxone, cold allodynia significantly decreased in rats with HCCs (P < 0.05), while the degree of cold allodynia in control animals was unaltered. CONCLUSIONS: From these results, it appears that HCCs have a possibility as an analgesic source for transplants delivering pain-reducing neuroactive substances.

Molecular Biological Characteristics of Differentiated Early Gastric Cancer on the Basis of Mucin Expression

BACKGROUND: It is clear that the biologic characteristics of gastric cancer are different on the basis of mucin phenotypes. However, there are unabated controversies on the exact biologic differences of mucin expression in gastric cancer. METHODS: We analyzed various protein expressions and microsatellite instability (MSI) status based on mucin expression in 130 differentiated early gastric adenocarcinoma cases. Furthermore, we evaluated the genomic alternation in 10 selected differentiated early gastric adenocarcinoma cases using array based comparative genomic hybridization (aCGH). RESULTS: Intestinal mucin predominant subtype showed significantly elevated p53 protein and caudal-related homeobox 2 expression, and delocalization of beta catenin expressions compared to the gastric mucin predominant subtype. On MSI status, the gastric mucin predominant subtype more frequently showed unstable status than the intestinal mucin predominant subtype. CGH study showed more frequent chromosomal gain and loss in the intestinal mucin predominant subtype than the gastric mucin predominant subtype, albeit without statistical significance. Interestingly, there were significant differences in chromosomal alternation between four mucin phenotypes. CONCLUSIONS: Study results suggest possible different points of biologic behaviors in early differentiated gastric adenocarcinomas by mucin expression type.