Effect of first epinephrine administration time on cerebral perfusion pressure and cortical cerebral blood flow in a porcine cardiac arrest model.

OBJECTIVE: The optimal time for epinephrine administration and its effects on cerebral blood flow (CBF) and microcirculation remain controversial. This study aimed to assess the effect of the first administration of epinephrine on cerebral perfusion pressure (CePP) and cortical CBF in porcine cardiac arrest model. METHODS: After 4 min of untreated ventricular fibrillation, eight of 24 swine were randomly assigned to the early, intermediate, and late groups. In each group, epinephrine was administered intravenously at 5, 10, and 15 min after cardiac arrest induction. CePP was calculated as the difference between the mean arterial pressure and intracranial pressure. Cortical CBF was measured using a laser Doppler flow probe. The outcomes were CePP and cortical CBF measured continuously during cardiopulmonary resuscitation (CPR). Mean CePP and cortical CBF were compared using analysis of variance and a linear mixed model. RESULTS: The mean CePP was significantly different between the groups at 6-11 min after cardiac arrest induction. The mean CePP in the early group was significantly higher than that in the intermediate group at 8-10 min and that in the late group at 6-9 min and 10-11 min. The mean cortical CBF was significantly different between the groups at 9-11 min. The mean cortical CBF was significantly higher in the early group than in the intermediate and late group at 9-10 min. CONCLUSION: Early administration of epinephrine was associated with improved CePP and cortical CBF compared to intermediate or late administration during the early period of CPR.

Prediction of Increased Intracranial Pressure in Traumatic Brain Injury Using Quantitative Electroencephalogram in a Porcine Experimental Model.

Continuous and non-invasive measurement of intracranial pressure (ICP) in traumatic brain injury (TBI) is important to recognize increased ICP (IICP), which can reduce treatment delays. The purpose of this study was to develop an electroencephalogram (EEG)-based prediction model for IICP in a porcine TBI model. Thirty swine were anaesthetized and underwent IICP by inflating a Foley catheter in the intracranial space. Single-channel EEG data were collected every 6 min in 10 mmHg increments in the ICP from baseline to 50 mmHg. We developed EEG-based models to predict the IICP (equal or over 25 mmHg) using four algorithms: logistic regression (LR), naive Bayes (NB), support vector machine (SVM), and random forest (RF). We assessed the performance of each model based on the accuracy, sensitivity, specificity, and AUC values. The accuracy of each prediction model for IICP was 0.773 for SVM, 0.749 for NB, 0.746 for RF, and 0.706 for LR. The AUC of each model was 0.860 for SVM, 0.824 for NB, 0.802 for RF, and 0.748 for LR. We developed a machine learning prediction model for IICP using single-channel EEG signals in a swine TBI experimental model. The SVM model showed good predictive power with the highest AUC value.

Hypertonic versus isotonic crystalloid infusion for cerebral perfusion pressure in a porcine experimental cardiac arrest model.

BACKGROUND: The effect of intravenous (IV) fluid administration type on cerebral perfusion pressure (CePP) during cardiopulmonary resuscitation (CPR) is controversial. The purpose of this study was to evaluate the association between IV fluid type and CePP in a porcine cardiac arrest model. METHODS: We randomly assigned 12 pigs to the hypertonic crystalloid, isotonic crystalloid and no-fluid groups. After 4 min of untreated ventricular fibrillation (VF), chest compression was conducted for 2 cycles (CC only). Chest compression with IV fluid infusion (CC + IV) was followed for 2 cycles. Advanced life support, including defibrillation and epinephrine, was added for 8 cycles (ALS phase). Mean arterial pressure (MAP), intracranial pressure (ICP) and CePP were measured. A paired t-test was used to measure the mean difference in CePP. RESULTS: Twelve pigs underwent the experiment. The hypertonic crystalloid group showed higher CePP values than those demonstrated by the isotonic crystalloid group from ALS cycles 2 to 8. The MAP values in the hypertonic group were higher than those in the isotonic group starting at ALS cycle 2. The ICP values in the hypertonic group were lower than those in the isotonic group starting at ALS cycle 4. From ALS cycles 2 to 8, the reduction in the mean difference in the isotonic group was larger than that in the other groups. CONCLUSION: In a VF cardiac arrest porcine study, the hypertonic crystalloid group showed higher CePP values by maintaining higher MAP values and lower ICP values than those of the isotonic crystalloid group.

Prediction of cerebral perfusion pressure during CPR using electroencephalogram in a swine model of ventricular fibrillation.

BACKGROUND: Measuring the quality of cardiopulmonary resuscitation (CPR) is important for improving outcomes in cardiac arrest. Cerebral perfusion pressure (CePP) could represent cerebral circulation during CPR, but it is difficult to measure non-invasively. In this study, we developed the electroencephalogram (EEG) based brain index (EBRI) derived from EEG signals by machine learning techniques, which could estimate CePP accurately in a porcine cardiac arrest model. METHODS: We conducted a randomised crossover study using nine female pigs. After 1 min of untreated ventricular fibrillation, we performed CPR with 12 different 2-min tilting angle sessions, including two different head-up tilt (HUT) angles (30°, 15°) twice, horizontal angle (0°) four times and two different head-down tilt (HDT) angles (-15°, -30°) twice with the random order. We collected EEG signals using a single channel EEG electrode in real-time during CPR. We derived the EBRI models to predict the CePP classified by the 5 or 10 groups using three different machine learning algorithms, including the support vector machine (SVM), k-nearest neighbour (KNN) and random forest classification (RFC) method. We assessed the accuracy, sensitivity and specificity of each model. RESULTS: The accuracy of the EBRI model using an SVM algorithm in the 5-group CePP classification was 0.935 with a standard deviation (SD) from 0.923 to 0.946. The accuracy in the 10-group classification was 0.904 (SD: 0.896, 0.913). The accuracy of the EBRI using the KNN method in the 5-group classification was 0.927 (SD: 0.920, 0933) and in the 10-group was 0.894 (SD: 0.880, 0.907). The accuracy of the RFC algorithm was 0.947 (SD: 0.931, 0.963) in the 5-group classification and 0.920 (SD: 0.911, 0.929) in the 10-group classification. CONCLUSION: We developed the EBRI model using non-invasive acquisition of EEG signals to predict CePP during CPR. The accuracy the EBRI model was 0.935, 0.927 and 0.947 for each machine learning algorithm, and the EBRI could be used as a surrogate indicator for measuring cerebral perfusion during CPR.

A peculiar case report of extraovarian Brenner tumor arising in the omentum.

BACKGROUND: Brenner tumors almost always develop in the ovary. Exceptionally, extraovarian Brenner tumors have been reported in the lower abdomen or pelvic organs. Here, we introduce a peculiar case of an extraovarian Brenner tumor arising in the omentum. CASE PRESENTATION: A 43-year-old woman presented with a palpable abdominal mass. Computed tomography (CT) scan revealed a 9.0-cm solid mass in the omentum. The tumor was not associated with pelvic structures, including the ovaries. It was excised under the clinical impression of an extragastrointestinal stromal tumor or neurogenic tumor. Grossly, the mass was a well-circumscribed solid tumor, with yellow-tan cut surface and minute cystic spaces. Microscopically, the tumor showed well-defined epithelial nests with variable cystic changes embedded in an abundant fibrous stroma. The cells within the nests were reminiscent of benign urothelial cells in that they had oval, frequently grooved nuclei. The epithelial cells focally showed a gradual transition into the surrounding stromal cells with short spindled features. The urothelium-like cells were positive for pancytokeratin, WT-1, p63, CK7, uroplakin-III, and GATA-3 but were negative for CD34, CD10, CK20, c-KIT, DOG-1, PAX-8, and calretinin. Morphological and immunohistochemical features of the tumor were the same as an ovarian Brenner tumor, and so it was diagnosed as an extraovarian Brenner tumor. CONCLUSIONS: Although the location of the tumor was very unusual, we could diagnose the tumor as an extraovarian Brenner tumor on the basis of the histologic and immunohistochemical findings. This is the first case of extraovarian Brenner tumor arising in the omentum near the stomach ever reported in the English literature.

Primary mucinous cystadenoma of the spermatic cord within the inguinal canal.

We report a hitherto not documented case of primary mucinous cystadenoma arising in the spermatic cord within the right inguinal canal of a78-year-old man. The tumor was painless, hard and mobile. A computed tomography scan on the pelvis revealed an oval shaped, low attenuation mass, measuring 5.0x2.5x2.1 cm, that was present adjacent to the vas deferens. Grossly, the excised mass was multicystic mucinous tumor, filled with thick mucoid materials. Microscopically, the cystic wall was irregularly thickened. The cystic epithelium commonly showed short papillae lined by a single layer of columnar to cuboidal mucinous epithelial cells without significant stratification or cytologic atypia. Goblet cells were also frequently present. Immunohistochemically, the neoplastic cells showed positive reaction to carcinoembryonic antigen, cytokeratin 20, CDX2, epithelial membrane antigen, and CD15. However, they were negative for PAX8 and Wilms' tumor 1 protein. Pathological diagnosis was a papillary mucinous cystadenoma of the spermatic cord. Although mucinous cystadenoma in this area is extremely rare, it is important that these lesions be recognized clinically and pathologically in order to avoid unnecessary radical surgery. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1720965948762004.

Reticulated myxoid tumor of the tongue: 2 cases supporting an expanded clinical and immunophenotypic spectrum of ectomesenchymal chondromyxoid tumor of the tongue.

An ectomesenchymal chondromyxoid tumor (ECMT) is a rare neoplasm that exclusively occurs in the anterior dorsum of the tongue. The tumor consists of small round to fusiform or spindle cells with myxoid or chondroid stroma. The tumor consistently shows a positive reaction with glial fibrillary acidic protein antibodies, especially polyclonal antibodies. We report 2 cases of reticulated myxoid tumors arising in the tongue. One tumor occurred in the posterior dorsum of the tongue and another in the anterior. Both tumors showed characteristic morphology of ECMT; however, both were negative for reactions with monoclonal and polyclonal glial fibrillary acidic protein antibodies. On the basis of morphology, they are thought to be belonging to ECMT. Hence, we suggest that ECMT can show broader spectrum of clinical and immunophenotypic feature.

Lymph node metastasis from intestinal-type early gastric cancer: experience in a single institution and reassessment of the extended criteria for endoscopic submucosal dissection.

BACKGROUND: Given the increasing use of endoscopic resection as a therapeutic modality for cases of early gastric cancer (EGC), it is very important to define strict criteria for the use of endoscopic mucosal resection and endoscopic submucosal dissection. To date, the criteria are almost entirely based on Japanese literature evaluating the risk of lymph node (LN) metastasis in patients with EGC. OBJECTIVE: To analyze our own experience with the factors affecting LN metastasis and to reappraise the extended criteria for endoscopic submucosal dissection. DESIGN: Retrospective, single-center study. SETTING: University teaching hospital. PATIENTS: This study involved 478 patients who underwent gastrectomy with LN dissection (n = 270, mucosal [m] EGC; n = 208, submucosal [sm] EGC). INTERVENTION: Gastrectomy with LN dissection. MAIN OUTCOME MEASUREMENTS: LN metastasis. RESULTS: Overall, 12.6% (60/478) of patients with EGCs presented with LN metastasis (mEGC, 3.0% [8/270], smEGC, 25.0% [52/208]). Increased size, macroscopic type (elevated), depth of invasion, and lymphovascular invasion were associated with LN metastasis. In 270 cases of mEGC, there was no relationship between clinicopathologic features and LN metastasis. In the smEGC group, size, depth of invasion, and lymphovascular emboli were associated with an increased risk of LN metastasis. Significantly, LN metastasis was noted in EGCs falling within established extended endoscopic submucosal dissection criteria, that is, intestinal-type mucosal cancer of any size without ulcer and no lymphovascular emboli (2/146 [1.4%]) or < or =3 cm with no lymphovascular emboli and irrespective of the presence of ulceration (2/126 [1.6%]) or intestinal-type submucosal cancer (sm1, <500 microm) without lymphovascular invasion and measuring < or =3 cm in size (3/20 [15.0%]). LIMITATIONS: Retrospective review of a single-center study. CONCLUSION: We recommend that more centers survey their experiences of LN metastasis in cases of EGC to refine the criteria for endoscopic submucosal dissection as a therapeutic modality of intestinal-type EGC.

Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings.

Gastroblastoma is a rare gastric epitheliomesenchymal biphasic tumour composed of spindle and epithelial cells, reported by Miettinen et al in a series of three cases in 2009. All those cases arose in stomachs of young adults. Neither the epithelial nor the mesenchymal component displayed sufficient atypia to diagnose a carcinosarcoma or other malignancy. On immunohistochemistry, the epithelial component expressed cytokeratin, and the mesenchymal component was positive for vimentin and CD10. Miettinen et al designated these neoplasms as gastroblastomas based on their similarities with other childhood blastomas such as pleuropulmonary blastoma and nephroblastoma. This report describes a probable fourth case of this unique type of neoplasm. The present case arose in the gastric antrum of a 9-year-old boy. While similarities were evident with the other cases, there were some differences. The epithelial component was more predominant and showed more mature morphology. Immunohistochemically, the epithelial component showed immunolabelling for c-KIT and CD56. The mesenchymal component was only focally positive for CD10. Ultrastructually, desmosomes and microvilli were found supporting a truly epithelial lesion.

Accuracy of high-frequency catheter-based endoscopic ultrasonography according to the indications for endoscopic treatment of early gastric cancer.

BACKGROUND AND AIM: The development of endoscopic treatment, such as endoscopic submucosal dissection, extends the indications for endoscopic resection in patients with early gastric cancer (EGC). Endoscopic ultrasonography (EUS) is the first-choice imaging modality for determining the depth of invasion of gastric cancer. The aim of the present study was to prospectively assess the accuracy of EUS for determining the depth of EGC, according to the accepted/extended indications. METHODS: We prospectively included a total of 181 lesions in 178 patients, with an endoscopic diagnosis of EGC, who underwent EUS for staging the depth of tumor invasion using a 20-MHz catheter probe. We investigated the accuracy of EUS for determining the depth of endoscopically-suspected EGC and then analyzed the difference in the accuracy of EUS according to the accepted/extended indications. RESULTS: Of the 178 patients, five patients were dropped because of the absence of final histological results. For the 176 lesions in 173 patients, the accuracy of EUS assessment for the depth of tumor invasion was 80.7% (142 of 176 lesions). The accuracy of EUS for the lesions with accepted indications and with extended indications was 97.6% (40 of 41 lesions) and 83.6% (46 of 57 lesions), respectively (P = 0.040). Of the lesions with extended indications, the accuracy of EUS decreased especially for the lesions with ulceration and those with minute submucosal invasion (79.2% and 42.9%, respectively). CONCLUSIONS: The accuracy of EUS for the lesions with the extended indications was lower than that for the lesions with the accepted indications. In particular, lesions with ulceration and minute submucosal invasion should be carefully considered prior to endoscopic treatment by pretreatment EUS staging.

Expression of beta-catenin and its mechanism of delocalization in intestinal-type early gastric cancer based on mucin expression.

The biological characteristics of intestinal-type early gastric cancers (ICs) differ based on mucin phenotypes. Beta-catenin delocalization is a predictive marker of aggressive biological behavior (submucosal invasion and lymph node metastasis) of ICs. The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes. Therefore, in the current study, the expression and mechanisms of delocalization of beta-catenin were elucidated on the basis of mucin phenotypes in 109 cases of ICs. There was increased cytoplasmic and nuclear beta-catenin expression (delocalization) in ICs with a predominant intestinal mucin phenotype (ICIP; 46.3% [25/54 cases]) compared to ICs with a predominant gastric mucin phenotype (ICGP; 20% [11/55 cases]). There were no beta-catenin or APC mutations in ICs. APC promoter hypermethylation was present in 49 of 105 (46.7%) cases of ICs. There was a significant relationship between APC promoter hypermethylation and beta-catenin delocalization in ICs, especially in ICIPs. There was no relationship between beta-catenin delocalization and APC gene loss of heterozygosity in ICs. In conclusion, we showed that beta-catenin delocalization was more evident in ICIPs, and APC promoter hypermethylation might play a role in delocalization of beta-catenin, especially in ICIPs.

Inactivation of O6-methylguanine-DNA methyltransferase in soft tissue sarcomas: association with K-ras mutations.

The DNA-repair protein O(6)-methylguanine-DNA methyltransferase removes alkyl adducts from the O(6)-position of guanine. The adducts can mispair with T during DNA replication, resulting in a G-to-A mutation. Epigenetic inactivation of O(6)-methylguanine-DNA methyltransferase has been found in human neoplasia and is considered one of the implicated factors in chemoresistance. Sixty-two patients with soft tissue sarcomas were analyzed with regard to the status of O(6)-methylguanine-DNA methyltransferase protein expression status using immunohistochemistry and promoter hypermethylation of the MGMT gene using methylation-specific PCR. G-to-A transitions in codons 12 and 13 of the K-ras oncogene were investigated using PCR and direct automated sequencing analysis. A loss of O(6)-methylguanine-DNA methyltransferase expression was noted in 20 (32.3%) cases of 62 total soft tissue sarcomas. The MGMT promoter hypermethylation rate was 33.9% (21/62 cases). Of the 54 sarcomas evaluated, K-ras mutations were found in only 2 (3.7%) cases. Loss of O(6)-methylguanine-DNA methyltransferase expression and MGMT promoter hypermethylation showed a significant association with high American Joint Committee on Cancer stage, high French Federation of Cancer Centers grade, and aggressive behavior. On multivariate analysis, these were not an independently significant prognostic factors. However, when the group receiving chemotherapy was analyzed (n = 27), loss of O(6)-methylguanine-DNA methyltransferase expression was correlated with worse survival on multivariate analysis (P = .024). MGMT promoter hypermethylation status had a strong correlation with loss of O(6)-methylguanine-DNA methyltransferase expression (P = .000). Our results suggest that MGMT promoter hypermethylation and loss of O(6)-methylguanine-DNA methyltransferase expression tend to be associated with poor prognosis and that the loss of O(6)-methylguanine-DNA methyltransferase protein expression frequently occurs via MGMT promoter hypermethylation. However, MGMT promoter hypermethylation was not significantly associated with point mutations of K-ras at codons 12 and 13 in sarcomas.

[Pathologic diagnosis of gastric epithelial neoplasia].

Gastric epithelial neoplasia is a very common disease entity in Korea, encompassing gastric adenoma and adenocarcinoma. There are still discrepancies in pathologic diagnosis of gastric epithelial neoplasia between Western and Japanese pathologists after Vienna consensus classification. With increasing use of endoscopic therapy such as endoscopic mucosal resection and endoscopic submucosal dissection, it is very important to agree on the consensus criteria in the diagnosis of gastric epithelial neoplasia among pathologists in Korea. On this background, the current concepts, and contemporary issues of definition, diagnostic and classification criteria of gastric epithelial neoplasia were reviewed.