Treatment Guidelines for Branch Duct Type Intraductal Papillary Mucinous Neoplasms of the Pancreas: When Can We Operate or Observe?

Background The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN. Methods We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea. Results Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor ≤2 cm without a mural nodule was 9.2%, for a tumor of ≤2 cm plus a mural nodule was 25%, and for other conditions such as tumor >2 cm, >25%. Conclusions Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of ≤2 cm without a mural nodule.     

Masticatory muscle reaction in simulated low-velocity rear-end impacts

AIMS: To evaluate the electromyographic (EMG) activity of masseter and temporalis muscles in relation to impact awareness, gender, impact magnitude, and kinematics of head movement in simulated low-velocity rear-end impacts. METHODS: Twenty-nine individuals (17 men and 12 women) were subjected in random order to 3 rear-end impacts: 2 unexpected impacts (chair accelerations of 4.5 m/s2 and 10.1 m/s2) and 1 expected impact (chair acceleration of 10.1 m/s2). The EMG activity of the deep and superficial masseter muscle was recorded bilaterally. EMG activity was also recorded for the left anterior temporalis muscle. Angular acceleration and angular displacement of the head were also recorded. The temporal relationship between onset of the masticatory muscle activity and maximum peak of the kinematics of head movement was determined. RESULTS: The magnitude of normalized masticatory EMG activity ranged from 1.4 to 1.8 times higher (P < .05) for fast unexpected impacts compared to slow unexpected impacts in all masticatory muscles. The magnitude of normalized anterior temporalis EMG peak response ranged from 1.8 to 2.5 times higher (P < .05) in female subjects than in male subjects for all impacts. No significant differences were identified for impact awareness in the magnitude of normalized EMG activity for any masticatory muscle. No significant differences were identified with respect to timing of masticatory muscle response (P > .05). CONCLUSION: EMG activity increased with increased impact magnitude. Temporal and amplitude awareness of a simulated impact did not produce a difference in the masticatory muscle response. Gender differences were identified in the anterior temporalis muscle response. The onset of the masticatory muscle response occurred after peak angular acceleration of the head but prior to peak angular displacement of the head.     

Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha‐2‐HS‐glycoprotein

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2‐HS‐glycoprotein gene (AHSG) and its protein, fetuin‐A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA‐dependent manner. In HepG2 cells treated with 300 μmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 μmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA‐overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid‐induced ER stress markers, CHOP, Bip, ATF‐6, XBP‐1, ATF‐4, and PERK. In addition, in the high‐fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one‐third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p‐AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.     

Expression of cyclooxygenase-2 in cholangiocarcinoma: correlation with clinicopathological features and prognosis

BACKGROUND AND AIMS: No information is available on the nature of the correlation between cyclooxygenase-2 (COX-2) expression and the clinicopathological features and prognosis of cholangiocarcinoma (CC). The goal of the present study was to determine the possible roles and clinical significance of COX-2 expression in CC. METHODS: We investigated the immunohistochemical expression of COX-2 in 102 patients with CC with respect to clinicopathological characteristics, namely evidence of Clonorchis sinensis infection, proliferation index (PI, assessed by Ki-67 expression), apoptotic index (AI, assessed by TUNEL stain), and microvessel density (MVD, assessed by CD34 expression). Evidence of C. sinensis infection was assessed by the microscopic examination of stools for C. sinensis ova, serological testing (ELISA), and the detection of peripheral bile duct dilations by imaging studies. RESULTS: An immunohistochemical investigation demonstrated the immunolabeling of tumor cells, mainly in the cytoplasmic and perinuclear regions, in 53 (52%) of the 102 patients with CC. No significant differences were found in terms of age, sex, tumor differentiation, involvement of the resection margin, presence of lymph nodes or liver metastases, or in pTNM stage between COX-2 positive and COX-2 negative patients. However, evidence of C. sinensis infection was more common in COX-2 positive patients (P < 0.05). No significant differences were found for PI, AI, MVD, or cumulative survival between COX-2 positive and COX-2 negative patients. CONCLUSION: Clonorchis sinensis infection is related to aberrant COX-2 expression in patients with CC. However, COX-2 expression is not related to clinical outcome in CC patients.     

Comparison of the Child-Turcotte-Pugh classification and the model for end-stage liver disease score as predictors of the severity of the systemic inflammatory response in patients undergoing living-donor liver transplantation

The aim of this study was to evaluate and compare the Child-Turcotte-Pugh (CTP) classification system and the model for end-stage liver disease (MELD) score in predicting the severity of the systemic inflammatory response in living-donor liver transplantation patients. Recipients of liver graft were allocated to a recipient group (n = 39) and healthy donors to a donor group (n = 42). The association between the CTP classification, the MELD scores and perioperative cytokine concentrations in the recipient group was evaluated. The pro-inflammatory cytokines measured included interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; the anti-inflammatory cytokines measured included IL-10 and IL-4. Cytokine concentrations were quantified using sandwich enzyme-linked immunoassays. The IL-6, TNF-α, and IL-10 concentrations in the recipient group were significantly higher than those in healthy donor group patients. All preoperative cytokine levels, except IL-6, increased in relation to the severity of liver disease, as measured by the CTP classification. Additionally, all cytokine levels, except IL-6, were significantly correlated preoperatively with MELD scores. However, the correlations diminished during the intraoperative period. The CTP classification and the MELD score are equally reliable in predicting the severity of the systemic inflammatory response, but only during the preoperative period.     

Nanoscale intracortical iron injection induces chronic epilepsy in rodent

We studied the electrophysiological, hemodynamic, and cytomorphological consequences of microhemorrhagic brain injury induced by a nanoscale iron injection. Of particular interest were the etiology, development, and treatment of epilepsy associated with this injury. We developed an animal model of chronic epilepsy using nanoscale injection into the adult mouse cortex. Although injection of nanoamounts of iron did not cause clear cell death or damage in the cortex, it elicited varying degrees of spontaneous epileptiform events that could be recorded under anesthesia 3 months postinjection. The influence of these chronic epileptiform events on neurovascular coupling was probed by directly stimulating the cortex ipsilateral to the epileptic focus and by measuring cerebral blood volume simultaneously in both hemispheres using intrinsic signal optical imaging. The ipsilateral hemodynamic response was dramatically lower in animals that exhibited longer, more frequent epileptiform events, but it was unchanged in animals displaying infrequent, short events. In contrast, the contralateral hemodynamic response was augmented in all iron‐injected animals compared with the control group. These abnormal hemodynamic responses in chronically epileptic animals were correlated with the degree of reduction in the number of GABAergic interneurons. Therefore, nanoscale iron injection, which mimics some aspects of microhemorrhagic brain injury, generated chronic, yet varying, degrees of spontaneous epileptiform events. Moreover, the severity of the epileptiform events corresponded to the degree of reduction in GABAergic interneurons in the iron‐injected hemisphere and the level of autoregulatory dysfunction of cerebral blood flow. © 2013 Wiley Periodicals, Inc.     

Evaluation of left ventricular mechanical dyssynchrony as determined by phase analysis of ECG-gated SPECT myocardial perfusion imaging in patients with left ventricular dysfunction and conduction disturbances

Background  Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms. Methods and Results  A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n=120), left bundle branch block (n=33), right bundle branch block (n=19), and ventricular paced rhythms (n=23) and were compared with normal control subjects (n=157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P<.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P=.001). Conclusions  A novel SPECT technique for describing left ventricular mechanical dyssyn-chrony has been developed and may prove useful in the evaluation of patients for CRT. This study was funded in part by a research grant from the Medtronic-Duke Strategic Alliance, of which Dr Borges-Neto is the primary investigator.     

Comparison of temporal lobectomies of children and adults with intractable temporal lobe epilepsy

Introduction

The aim of the study was to assess the difference in clinical characteristics and postsurgical outcomes between children and adults who have undergone temporal lobectomy (TL).

Materials and methods

We retrospectively reviewed the medical records of 52 patients who had undergone TL between 2006 and 2008. Nineteen patients were classified as children (≤18 years old), and 33 patients were classified as adults (>18 years old) according to the age when TL had been performed.

Results

Twelve of 19 (63.2%) children and 24 of 33 (72.7%) adults became seizure free. Rapid secondary generalization such as generalized tonic or tonic–clonic seizures showed a tendency to be more prominent in children (four of 19, 21.1%) than in adults (three of 33, 9.1%). Patients in childhood had significantly more multifocal discharges on interictal electroencephalography (EEG) (42.1%) compared to adults (15.2%, p?=?0.014). The mean extent of surgical excision was 5.0 cm in children and 4.1 cm in adults (p?=?0.001). The incidence of hippocampal sclerosis, the most common pathologic finding in the two groups, was 57.9% (11 of 19) in children and 78.8% (26 of 33) in adults. Malformations of cortical development were significantly more frequent in children (nine of 19, 47.4%) than in adults (seven of 33, 21.2%). Dual pathology was found in 31.6% of children and in 12.1% of adults. The intelligence quotient and memory quotient values in children with temporal lobe resection remained nearly steady during follow-up period without significant decline.

Conclusion

Patients undergoing TL during childhood compared to during adulthood had distinctively different interictal EEG, resectional extents, and pathologic findings.     

Calorie restriction (CR) reduces age-dependent decline of non-homologous end joining (NHEJ) activity in rat tissues

Even though CR has shown to enhance base excision repair (BER) and nucleotide excision repair (NER) capacities, it has not been reported whether CR can enhance non-homologous end joining (NHEJ) activity. To examine the effect of CR on NHEJ activity, ad libitum (AL)- and calorie restricted (CR)-dieted rats were used. Age-dependent decline of NHEJ activity was apparent in the lung, liver, and kidney and appeared to be slightly decreased in spleen. CR reduced age-dependent decline of NHEJ activity in all tissues, even though the extent of recovery was variable among tissues. Moreover, CR appeared to reduce age-dependent decline of XRCC4 protein level. These results suggest that CR could reduce age-dependent decline of NHEJ activity in various tissues of rats possibly through up-regulation of XRCC4.