Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production

Background

Because of the rarity and variety of pancreatic neuroendocrine tumors (PNETs), there have been few reports regarding the indication for lymph node dissection in patients with these tumors. This study aimed to evaluate the risk of lymph node metastasis of PNETs based on the tumor size and hormonal production.

Methods

Data for a total of 66 patients who had PNETs resected at our department between 1987 and 2010 were retrospectively studied. The clinicopathological features, including the disease-specific survival rate, were assessed based on the status of lymph node metastasis at the time of initial surgical resection. Then the cut-off point of tumor size to predict lymph node metastasis was estimated.

Results

There were 12 patients (18%) with lymph node metastasis. The frequency of lymph node metastasis tended to be higher in gastrinomas than that in other tumors (43 vs. 15%; P?=?0.08). The size of PNETs with lymph node metastasis was significantly larger than that of the PNETs without metastasis (P?=?0.04). The postoperative survival rate in the PNET patients with lymph node metastasis was significantly lower than that in the patients without metastasis (P?Conclusions Non-gastrinomas with a tumor size of ≥15?mm and all gastrinomas would be an indication for pancreatectomy with lymph node dissection.     

Neural activity in the hippocampus predicts individual visual short‐term memory capacity

Although the hippocampus had been traditionally thought to be exclusively involved in long‐term memory, recent studies raised controversial explanations why hippocampal activity emerged during short‐term memory tasks. For example, it has been argued that long‐term memory processes might contribute to performance within a short‐term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short‐term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19–27 yr, nine males) while they performed a match‐to‐sample task requiring processing of object‐location associations (delay period = 900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K‐formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of “set size” in the posterior parietal cortex (PPC). In line with a “set size × group” interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity = 3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity = 5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance‐related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object‐location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating. © 2013 Wiley Periodicals, Inc.     

Minocycline suppresses experimental autoimmune encephalomyelitis by increasing tissue inhibitors of metalloproteinases

Matrix metalloproteinases (MMPs) that are secreted by activated T cells play a significant role in degradation of the extracellular matrix around the blood vessels and facilitate autoimmune neuroinflammation; however, it remains unclear how MMPs act in lesion formation and whether MMP‐targeted therapies are effective in disease suppression. In the present study, we attempted to treat experimental autoimmune encephalomyelitis (EAE) by administration of small interfering RNAs (siRNAs) for MMP‐2, MMP‐9, and minocycline, all of which have MMP‐inhibiting functions. Minocycline, but not siRNAs, significantly suppressed disease development. In situ zymography revealed that gelatinase activities were almost completely suppressed in the spinal cords of minocycline‐treated animals, while significant gelatinase activities were measured in the EAE lesions of control animals. However, MMP‐2 and MMP‐9 mRNAs and proteins in the spinal cords of treated rats were unexpectedly upregulated. At the same time, mRNA for tissue inhibitors of MMPs (TIMP)‐1 and ‐2 were also upregulated. The EnzChek Gelatinase/Collagenase assay using tissue containing native MMPs and TIMPs demonstrated that gelatinase activity levels in the spinal cords of treated rats were suppressed to the same level as those in normal spinal cord tissues. Finally, double immunofluorescent staining demonstrated that MMP‐9 immunoreactivities of treated rats were almost the same as those of control rats and that MMP‐9 and TIMP‐1 immunoreactivities were colocalized in the spinal cord. These findings suggest that minocycline administration does not suppress MMPs at mRNA and protein levels but that it suppresses gelatinase activities by upregulating TIMPs. Thus, MMP‐targeted therapies should be designed after the mechanisms of candidate drugs have been considered.     

Primary renal neuroblastoma with metastasis and matrix metalloproteinase‐14 expression

We herein report the rare case of a 4‐year–5‐month‐old boy who presented with primary renal neuroblastoma. The patient developed repeated lung and liver metastatic recurrences, but, following a combination of chemotherapy, radiation therapy and aggressive surgical resection, the patient is now in remission. To investigate the pathogenesis of lung metastasis, immunohistochemistry was performed for matrix metalloproteinase‐9 and ‐14 (MMP‐9 and MMP‐14), molecular markers of invasion, metastasis and angiogenesis in neuroblastoma. In the present case, MMP‐9 expression was not observed, but MMP‐14 expression was detected in the primary lesion and was more highly expressed in the metastatic lesion compared with the primary one. Given the MMP‐14 staining in other cases, expression of MMP‐14 may be associated with the aggressiveness of the tumor. This suggests that selected clones with high MMP‐14 expression in the primary tumor might metastasize and form MMP‐14‐rich lesions.