Pancreatic Acinar Cell Carcinoma: A Multi-institutional Study

Introduction  The presentation and outcome of patients with acinar cell carcinoma (ACC) of the pancreas compared to the more common ductal cell adenocarcinoma (DCA) may be distinct. This study combines the experience with ACC from multiple academic institutions to better understand its natural history and outcomes. Methods  This study is a multi-institutional retrospective review of patients with ACC. Results  Between 1988 and 2008, 17 patients were identified with pathologically confirmed ACC. Median age at presentation was 59 years. Common presenting symptoms were abdominal pain (60%), back pain (50%), and weight loss (45%). Fifteen patients underwent 16 operations: pancreaticoduodenectomy (nine), distal pancreatectomy (four), and exploratory laparotomy (three). Mean tumor size was 5.3 cm. American Joint Commission on Cancer tumor stages were stage I (two), stage II (eight), stage III (four), and stage IV (three). Overall, 1- and 5-year survival rates were 88% and 50%, respectively. In resected cases (13), 1- and 5-year survival rates were 92% and 53%, respectively. Median survival in resected cases was 61 months. This is in contrast to 1,608 patients with ductal cell adenocarcinoma who underwent resection identified from recent literature reports where the average median survival was only 24 months. There was no discernable difference in the outcomes of patients with ACC between United States and Germany patients. Conclusion  Acinar cell carcinoma of the pancreas is rare and appears to have a presentation and outcome distinct from the more common pancreatic DCA. Based upon these data, the outcome of patients with ACC is superior to that of DCA. Jesus M. Matos and C. Max Schmidt contributed equally to this work. This paper was presented at the Society for Surgery of the Alimentary Tract (SSAT) in San Diego, California in May 2008.     

Construction of periventricular white matter hyperintensity maps by spatial normalization of the lateral ventricles

Subcortical and periventricular white matter hyperintensities (WMHs) may have different associations with cognition and pathophysiology. The aim of the present study is to develop an automated method for construction of periventricular WMH maps that enables the analysis of between-group differences in WMH location and characteristics in the periventricular region without the requirement of prior boundary definition. To avoid influence of WMHs on spatial normalization, a reference image of the lateral ventricles was constructed based on images of 24 subjects. Construction was not biased to a single subject. WMHs were segmented by k-nearest neighbor-based classification of magnetic resonance inversion recovery and fluid attenuated inversion recovery images. Cerebrospinal fluid segmentations of individual subjects were nonrigidly mapped to the reference image of the lateral ventricles. The subject's WMHs were transformed to the reference space accordingly. Spatial normalization accuracy was validated using measures of overlap and of displacement relative to the boundary of the lateral ventricles. After spatial normalization, the boundaries of the lateral ventricles closely matched the reference image and in an area of approximately 1 cm around the lateral ventricles the relative displacement was less than 1 mm. To illustrate the method, it was applied to 61 patients with Type 2 diabetes and 26 control subjects, whereupon periventricular WMH maps were constructed and compared. The proposed method is particularly suited to analyze WMH distribution differences at the level of the lateral ventricles between large groups of patients.     

Causality assessment of drug-induced hepatotoxicity: promises and pitfalls

Drug-induced liver injury is the leading cause of acute liver failure in the United States, but the ability to ascribe hepatic injury confidently to a specific drug remains a challenging and often difficult pursuit. This article explores the ongoing challenges inherent in what is currently a clinical process of elimination made in the attempt of assigning causality in drug-induced liver injury. In particular, it points out the shortcomings and pitfalls that often limit the applicability of the causality-assessment methodologies currently in use.     

Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM: To evaluate the role of N-myc downstream-regulated gene 1 (NDRG1) expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS: Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α (HIF-1α),we examined NDRG1 expression together with p53 and HIF-1α by immunohistochemistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed.in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion,venous invasion,depth of invasion,histopathological type,and Dukes' stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type,Dukes' stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly,Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However,in p53-positive US cases,NDRG1 positivity correlated significantly with better survival. In addition,NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and Ⅳ tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors,strong NDRG1 staining in p53-positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION: NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.     

Maternal mental health and child behaviour problems at 2 years: findings from the Pacific Islands Families Study

OBJECTIVE: The present study investigated associations between the timing and persistence of maternal psychological disorder and child behaviour problems in a cohort of Pacific 2-year-old children in New Zealand. METHOD: Mothers of a cohort of 1,398 Pacific infants born in South Auckland, New Zealand were interviewed when their children were 6 weeks, 12 and 24 months of age. Within the context of a wider interview, data regarding maternal mental health were obtained at these times and maternal reports of child behaviour were gathered when the children were 2 years old. RESULTS: Prevalence rates for internalizing problems were significantly higher in children of mothers who had self-reported symptoms of psychological disorder (11.9% in no symptoms, 27.8% in early symptoms of postnatal depression, 21.1% in late symptoms of psychological disorder and 42.9% in persistent or recurrent symptoms). The adjusted odds ratio (OR) of a child having internalizing problems was 1.38 (95% confidence interval (CI): 0.79-2.43) in those of mothers reporting early symptoms of postnatal depression, 1.45 (95%CI: 0.85-2.49) in late symptoms of psychological disorder, and 2.93 (95%CI: 1.54-5.57) in persistent or recurrent symptoms relative to the no symptoms group. For externalizing problems, the effects of maternal psychological disorder were not significant. CONCLUSIONS: Maternal persistent or recurrent symptoms of psychological disorder may contribute to the behaviour problems of children as young as 2 years old. However, the timing of disorder, whether it is infant or toddler exposure, does not appear to be as crucial. Improved understanding of the associations between maternal psychological disorder and early child behaviour problems may help maternal and child health professionals design appropriate and effective screening and intervention programs to help Pacific mothers and children.     

Cerebral embolic ischemia in rats: correlation of stroke severity and functional deficit as important outcome parameter

The embolic MCA occlusion model in rats is used for recanalisation studies in acute stroke. In addition to the determination of lesion size, the assessment of functional outcome may improve the value of this model. Male Wistar rats were submitted to MCA clot embolism or sham surgery. In order to achieve a larger variety of lesion volume, 2 subgroups (each 7 animals) were subjected to differently sized emboli (30 and 40 mm). Follow-up period was 6 days. Outcome assessment consisted of a test battery including parallel bar crossing, observation of behaviour in an open field and an 8-arm maze and a neurological score with ten different sensorimotor and coordinative items. Animals were perfusion-fixed on day 7 (blinded examination). For both subgroups, there were significant impairments with regard to performance on the Neuro score, parallel bar crossing and maze exploration. Improvement was only partial during the follow-up period. On follow-up day 6, there was still a significant correlation between total infarct volume and functional outcome on the Neuro score (R=0.80, p=0.0006) and the exploration behaviour in the maze (R=0.66, p=0.01). Application of emboli with a length of 40 mm caused more functional impairment and a more extended lesion volume compared with 30 mm. We present outcome tests that provide quantitative and objective tools to test functional impairment in rats following embolic stroke.     

The neuropsychological basis of hypersociability in Williams and Down syndrome

People with Williams syndrome (WS) display indiscriminate approach toward strangers in everyday life. People with Down syndrome (DS) can also do so, but to a lesser degree. Inappropriate approach behavior is also characteristic of people with acquired amygdala damage and people with acquired frontal lobe impairment; given this, the developmental disorder of social approach seen in WS and perhaps also DS might be due to poor emotion recognition (due to abnormal amygdala functioning) or poor control of behavior (due to frontal lobe abnormality). A third account of this developmental disorder of social cognition can be couched in terms of heightened salience for social stimuli. We explored these three hypotheses by testing emotion recognition, social approach and frontal lobe functioning in people with WS and DS. Overall, our results were inconsistent with predictions from the amygdala and social salience hypotheses. In contrast, results from a battery of neuropsychological tasks suggested that abnormal social approach in WS and DS in everyday life is best explained by frontal lobe impairment, in particular, poor response inhibition.