Concomitant pancreatic and duodenal metastases 12 years after nephrectomy for renal cell carcinoma: a case report.

In selected patients with metastatic renal cell carcinoma, metastasectomy can achieve prolonged survival. Herein we report a patient with concomitant pancreatic and duodenal metastases occurring 12 years after total right nephrectomy for a renal cell carcinoma. The metastases were successfully treated by a pancreas-sparing duodenectomy and distal pancreatectomy. A 66-year-old man was referred to our hospital with a chief complaint of right upper abdominal pain. He had undergone laparoscopic total right nephrectomy for renal cell carcinoma 12 years before. Enhanced computed tomography showed hypervascular tumors in the pancreatic body and the descending duodenum near the papilla of Vater. Histopathological examination of endoscopic ultrasonography-guided fine needle aspiration cytology specimens revealed metastatic clear cell renal cancer. The patient underwent pancreas-sparing duodenectomy and distal pancreatectomy. He developed a pancreatic fistula after surgery that improved with conservative treatment, and has been free of evidence of recurrence up to 20 months postoperatively.

Time-course analysis of liver and serum galectin-3 in acute liver injury after alpha-galactosylceramide injection.

Galectin-3 is a beta-galactoside-binding lectin that plays important roles in diverse physiological functions, such as cell proliferation, apoptosis, and mRNA splicing. This protein is expressed on inflammatory cells and acts as a local inflammatory mediator. Recently, galectin-3 has been detected in several diseases, such as chronic liver, heart, and kidney diseases, diabetes, viral infection, autoimmune and neurodegenerative diseases, and tumors, and its role as a biomarker has attracted attention. Alpha-galactosylceramide is an artificially synthesized sphingolipid that can induce acute liver injury via the natural killer T pathway. However, the pathophysiological roles and kinetics of galectin-3 in acute liver injury are not fully understood. This study aimed to elucidate the expression and time course of galectin-3 in liver tissues during acute liver injury following alpha-galactosylceramide injection. Animals were histologically examined on days 1, 2, 4, and 7 after intraperitoneal injection of alpha-galactosylceramide, and the expressions of galectin-3 and ionized calcium-binding adaptor molecule 1 were analyzed. Notably, galectin-3 formed characteristic cluster foci, particularly on day 2 after injection. Cluster formation was not observed in chronic liver disease. Simultaneously, ionized calcium-binding adaptor molecule 1-positive cells were observed in the cluster foci. Serum galectin-3 levels increased on day 2 of treatment and correlated well with the number of galectin-3-positive cell clusters in the liver. Moreover, galectin-3 expression was an important mediator of the early phase of liver injury after alpha-galactosylceramide injection. These results suggest that serum galectin-3 may be a biomarker for the early diagnosis of acute liver injury and that clusters of galectin-3-positive cells may be a specific finding in acute liver injury.

Successful treatment of cervical and upper thoracic esophageal adenocarcinoma using induction chemotherapy followed by surgery: a case report.

Cervical esophageal adenocarcinoma has a low incidence rate and its treatment involves various strategies. We report a patient with locally advanced cervical to upper esophageal adenocarcinoma who was able to undergo induction chemotherapy and radical surgery. A 55-year-old man was diagnosed with a poorly differentiated adenocarcinoma between the cervical and upper thoracic esophagus. The primary lesion had infiltrated into the tracheal membrane and had metastasized into the cervical lymph nodes. The initial diagnosis was T4bN1M1 stage IVB. The lower edge of the tumor was close to the tracheal bifurcation, making it difficult to create a longitudinal tracheal foramen during surgery. Therefore, when biweekly-DCF therapy was performed as induction chemotherapy, the tumor shrank sufficiently and its infiltration into the tracheal membrane decreased subsequently. We performed total laryngopharyngoesophagectomy with three-field lymph node dissection and reconstruction using free jejunal grafts and subtotal stomach via a posterior mediastinum route and a permanent tracheal foramen as a radical surgery. The pathological diagnosis was T2/MP, N1, and the effect of chemotherapy was grade 2. Cervical esophageal adenocarcinoma was rare, but technically reliable and safe oncologic surgery was possible after induction chemotherapy.

ALDH1 and SALL4 Expression in Cell Block Samples from Patients with Lung Adenocarcinoma and Malignant Pleural Effusion.

Malignant pleural effusion (MPE) can accompany advanced lung adenocarcinoma. Recent studies suggest that MPE could contain a heterogeneous subpopulation of cells with stem-like properties, such as tumorigenicity and self-renewal, indicating that they could be the source of metastasis. Although previous studies analyzed the correlation between cancer stem cell (CSC) marker expression and clinical outcomes using lung cancer tissues, investigations regarding the association of MPE with CSC marker expression are limited. We performed immunohistochemistry to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and Sal-like 4 (SALL4) in 46 cell block samples of MPE from patients with lung adenocarcinoma. ALDH1-positive and SALL4-positive cancer cells in MPE were detected in 30 (65.2%) and 21 samples (45.7%), respectively. Cluster formation was detected in 26 samples (56.5%). The number of clusters was significantly higher in ALDH1-positive/SALL4-negative samples. SALL4 expression was inversely correlated with the cluster ratio (r = -0.356) and positively associated with the Ki-67 index (r = 0.326), suggesting that MPE cells with high SALL4 expression comprised the proliferative subpopulation. In conclusion, we demonstrated that MPE contains an ALDH1-positive/SALL4-negative subpopulation exhibiting cluster formation and a SALL4-positive proliferative subpopulation.

Characterization of kaposiform lymphangiomatosis tissue-derived cells.

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a recently characterized systemic lymphatic anomaly. Activation of RAS/MAPK and PI3K/AKT/mTOR pathways may affect KLA pathogenesis, but the cellular basis of KLA is unclear. Abnormal-spindle endothelial cells that express lymphatic endothelial cell (LEC) markers are characteristic of KLA histopathology. This study evaluated patient-derived KLA cells to establish their morphological and biological characteristics. PROCEDURE: We established cell lines from primary KLA tissues of two patients with KLA and examined their morphological and functional characteristics, messenger RNA and protein expression profiles, gene mutations, and responses to inhibitors of the RAS/MAPK and PI3K/AKT/mTOR pathways. RESULTS: Both KLA cell lines showed spindle-shaped morphology, stained positive for podoplanin (PDPN), and exhibited impaired tube-formation properties. They expressed LEC marker PDPN and mesenchymal stem cell markers (CD90, CD105) in the absence of endothelial cell markers (CD34, CD31, VWF), per real-time polymerase chain reaction. Both mTOR inhibitor rapamycin and MEK inhibitor trametinib inhibited growth of the two cell lines. A NRAS p.Q61R variant was found in one of two independent KLA tissue samples, but not in the KLA cells (per targeted next-generation sequencing); and KLA cells with this variant had elevated AKT phosphorylation levels. ERK phosphorylation levels were undetectable in both KLA cell lines. CONCLUSIONS: Inhibition of the RAS/MAPK and PI3K/AKT/mTOR pathways may represent potential therapeutic targets in KLA. These patient-derived KLA cell lines will be useful research tools to elucidate KLA etiology, and could pave the way for basic, translational, and preclinical studies of this disease.

Clinically relevant umbilical cord inflammation identified based on CD15-associated vasculitis patterning.

INTRODUCTION: Acute funisitis, a granulocyte-related inflammation of the umbilical cord, is associated with chorioamnionitis and perinatal adverse events. However, there is no efficient procedure for detecting clinically relevant umbilical cord inflammation. The objective of this study was to identify such inflammation, based on immunohistochemical assessment of umbilical cord vasculitis patterns. METHODS: Accordingly, 261 cases were retrieved from a single medical institute. Using the well-established granulocyte marker CD15, we developed a five-tier umbilical cord inflammation-scoring system. Additionally, previous morphological assessments from pathological reports were compared to the immunohistochemical findings. RESULTS: Analysis of results based on our new scoring system revealed that severe umbilical phlebitis (score 3) was significantly associated with maternal inflammatory response and that severe umbilical arteriophlebitis (score 4) was correlated with low umbilical arterial blood pH, a feature linked to fetal mortality and morbidity. These results corresponded with and were validated by the morphology-based assessments. Additionally, immunohistochemical analysis revealed the clinical and pathological relevance of vitelline vasculitis, a recently proposed condition. We found that analyzing three umbilical cord sections enabled superior detection of severe umbilical vasculitis than analyzing two sections. However, whether these sections were sampled from multiple distant sites or a single localized site did not significantly affect the detection of clinically relevant inflammation. DISCUSSION: CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation. CD15 immunohistochemistry is a potent tool for observing the patterns of clinically relevant umbilical vasculitis, especially in cases that were indeterminate according to morphology alone. Sampling three umbilical cord sections was an efficient procedure for addressing the spatial heterogeneity of umbilical cord inflammation.

Inhibition of FGF10-ERK signal activation suppresses intraductal papillary neoplasm of the bile duct and its associated carcinomas.

Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With KrasG12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early Stage Pathology.

The use of molecular biomarkers for the early detection of heart disease, before their onset of symptoms, is an attractive novel approach. Ideal molecular biomarkers, those that are both sensitive and specific to heart disease, are likely to provide a much earlier diagnosis, thereby providing better treatment outcomes. Galectin-3 is expressed by various immune cells, including mast cells, histiocytes and macrophages, and plays an important role in diverse physiological functions. Since galectin-3 is readily expressed on the cell surface, and is readily secreted by injured and inflammatory cells, it has been suggested that cardiac galectin-3 could be a marker for cardiac disorders such as cardiac inflammation and fibrosis, depending on the specific pathogenesis. Thus, galectin-3 may be a novel candidate biomarker for the diagnosis, analysis and prognosis of various cardiac diseases, including heart failure. The goals of heart disease treatment are to prevent acute onset and to predict their occurrence by using the ideal molecular biomarkers. In this review, we discuss and summarize recent developments of galectin-3 as a next-generation molecular biomarker of heart disease. Furthermore, we describe how galectin-3 may be useful as a diagnostic marker for detecting the early stages of various heart diseases, which may contribute to improved early therapeutic interventions.

Specific Deletion of p16INK4a with Retention of p19ARF Enhances the Development of Invasive Oral Squamous Cell Carcinoma.

The cyclin-dependent kinase inhibitor 2A (CDKN2A)/alternate reading frame (ARF) locus consists of two overlapping tumor suppressor genes, p16INK4a and p14ARF (p19ARF in mice), encoding two unrelated proteins in alternative reading frames. Previous reports suggest that p16INK4a and p14ARF alterations independently exhibit differential roles, and p16INK4a is more closely associated with a poor prognosis in oral cancer. However, the role of p16INK4a-specific loss in oral squamous cell carcinogenesis remains unclear. The authors assessed chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced multistep oral squamous cell carcinogenesis in mice carrying p16INK4a-specific loss with retention of the p19ARF gene (p16INK4a-/-). 4NQO-treated p16-/- mice exhibited a higher incidence and multiplicity of oral squamous cell carcinoma (OSCC) development relative to 4NQO-treated wild-type mice. 4NQO-treated p16INK4a-/- OSCC cells exhibited higher proliferation and up-regulation of Arf, transcription factor E2f1, tumor protein p63 (tp63), and oncogenic ΔNp63, an isoform p63, compared with observations in 4NQO-treated wild-type OSCC cells. Furthermore, the overexpression of oncogenic ΔNp63 was associated with human OSCC. In conclusion, these results in mice indicate the biological significance of p16INK4a-specific loss with retention of p19ARF in oral squamous cell carcinogenesis, and ΔNp63 may be a potential target for OSCC.

Multiple trauma including pelvic fracture with multiple arterial embolization: an autopsy case report.

BACKGROUND: Pelvic fracture with high energy trauma has a high mortality rate, especially in men. In addition, severe multiple trauma, major hemorrhage, and administration of red blood cells predict mortality in elderly patients with pelvic fracture. We herein report a rare case in which multiple arterial embolization occurred after pelvic fracture. CASE PRESENTATION: An 83-year-old male cyclist was transported to our hospital after being struck by a car. On arrival, he was diagnosed with multiple trauma, including rib fractures with hemothorax, lumbar fractures of the transverse process, and injuries in the right acetabulum, left adrenal gland, and liver. He underwent massive transfusion and transcatheter arterial embolization due to extravasation from the right superior gluteal artery and left adrenal gland. On the second day, owing to right lower leg ischemia, serum creatinine kinase and myoglobin levels were markedly elevated from the reference value; hence, a right above-knee amputation was performed 12 h after the accident. However, both protein levels remained high after amputation, resulting in acute renal injury, which was treated via hemodiafiltration on hospital day 3. In addition, sustained low efficiency hemodialysis and plasma exchange were performed on hospital day 4. Despite these treatments, the patient's hemodynamics did not improve, and he died on hospital day 8. The autopsy revealed necropsy of the iliopsoas muscles and the digestive tract. CONCLUSIONS: The causes of the patient's death were considered to be persistent rhabdomyolysis and severe hypotension due to iliopsoas necrosis and peritonitis due to digestive tract necrosis. Multiple arterial embolization caused by consumption coagulopathy associated with multiple trauma may account for severe outcomes in this case.

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases.

Galectin-3 is a ß-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.

Treatment Strategies Based on Histological Targets against Invasive and Resistant Glioblastoma.

Glioblastoma (GBM) is the most common and the most malignant primary brain tumor and is characterized by rapid proliferation, invasion into surrounding normal brain tissues, and consequent aberrant vascularization. In these characteristics of GBM, invasive properties are responsible for its recurrence after various therapies. The histomorphological patterns of glioma cell invasion have often been referred to as the "secondary structures of Scherer." The "secondary structures of Scherer" can be classified mainly into four histological types as (i) perineuronal satellitosis, (ii) perivascular satellitosis, (iii) subpial spread, and (iv) invasion along the white matter tracts. In order to develop therapeutic interventions to mitigate glioma cell migration, it is important to understand the biological mechanism underlying the formation of these secondary structures. The main focus of this review is to examine new molecular pathways based on the histopathological evidence of GBM invasion as major prognostic factors for the high recurrence rate for GBMs. The histopathology-based pharmacological and biological targets for treatment strategies may improve the management of invasive and resistant GBMs.

Time-course analysis of cardiac and serum galectin-3 in viral myocarditis after an encephalomyocarditis virus inoculation.

Galectin-3 is a ß-galactoside-binding lectin which is important in cell proliferation and apoptotic regulation. Recently, serum galectin-3 has been shown to have prognostic value as a biomarker in heart failure. Encephalomyocarditis virus (EMCV) can cause severe myocarditis, congestive heart failure and dilated cardiomyopathy as well as encephalitis in various animals including mice. The pathophysiological role of galectin-3 in acute myocarditis following viral infection is not fully understood. The goal of this study is to determine the cardiac localization and the time-course of galectin-3 expression in heart failure after viral inoculation with EMCV. At 12, 24, 48, 96 hours, 7 and 10 days after intraperitoneal EMCV inoculation, animals were examined histologically and analyzed for the expression of galectin-3 and Iba1. Galectin-3 was up-regulated in degenerated fibrotic lesions of cardiac tissues 96 hours after viral inoculation and were followed by myocardial fibrosis. At the same time, Iba1 positive macrophages were observed within the inflammatory sites. A time-course correlation between the number of galectin-3 positive cells and the cardiac area of degenerated fibrotic lesions was detected-serum galectin-3 increased at 96 hours and correlated well with the number of cardiac galectin-3 positive cells. Our results indicate that galectin-3 expression may be a useful biomarker of cardiac fibrotic degeneration in acute myocarditis following viral infection. In addition, measuring serum galectin-3 levels might be an early diagnostic method for detecting cardiac degeneration in acute myocarditis.

Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia.

Ischemia-reperfusion injuries produce reactive oxygen species that promote the peroxide lipid oxidation process resulting in the production of an endogenic lipid peroxide, 4-hydroxy-trans-2-nonenal (4-HNE), a highly cytotoxic aldehyde that induces cell death. We synthesized a novel 4-HNE scavenger - a carnosine-hydrazide derivative, l-carnosine hydrazide (CNN) - and examined its neuroprotective effect in a model of transient ischemia. PC-12 cells were pre-incubated with various doses (0-50 mmol/L) of CNN for 30 min, followed by incubation with 4-HNE (250 µM). An MTT assay was performed 24 h later to examine cell survival. Transient ischemia was induced by bilateral common carotid artery occlusion (BCCO) in the Mongolian gerbil. Animals were assigned to sham-operated (n = 6), placebo-treated (n = 12), CNN pre-treated (20 mg/kg; n = 12), CNN post-treated (100 mg/kg; n = 11), and histidyl hydrazide (a previously known 4-HNE scavenger) post-treated (100 mg/kg; n = 7) groups. Heat shock protein 70 immunoreactivity in the hippocampal CA1 region was evaluated 24 h later, while delayed neuronal death using 4-HNE staining was evaluated 7 days later. Pre-incubation with 30 mmol/L CNN completely inhibited 4-HNE-induced cell toxicity. CNN prevented delayed neuronal death by >60% in the pre-treated group (p < 0.001) and by >40% in the post-treated group (p < 0.01). Histidyl hydrazide post-treatment elicited no protective effect. CNN pre-treatment resulted in high heat shock protein 70 and low 4-HNE immunoreactivity in CA1 pyramidal neurons. Higher 4-HNE immunoreactivity was also found in the placebo-treated animals than in the CNN pre-treated animals. Our novel compound, CNN, elicited highly effective 4-HNE scavenging activity in vitro. Furthermore, CNN administration both pre- and post-BCCO remarkably reduced delayed neuronal death in the hippocampal CA1 region via its induction of heat shock protein 70 and scavenging of 4-HNE.

Novel Indirect Revascularization Technique with Preservation of Temporal Muscle Function for Moyamoya Disease Encephalo-Duro-Fascio-Arterio-Pericranial-Synangiosis: A Case Series and Technical Note.

BACKGROUND: Direct and/or indirect bypass surgery is the established approach for preventing stroke in patients with moyamoya disease. However, conventional indirect revascularization, including encephalo-myo-synangiosis, has some disadvantages associated with the mass effect of the temporal muscle under the bone flap and postsurgical depression in the temporal region. We devised a novel indirect revascularization method, using only the temporal fascia, to address the aforementioned disadvantages. METHODS: A skin incision was performed along the superficial temporal artery. The temporal fascia was cut such that the base of the fascia flap was on the posterior side. The fascia and temporal muscles were dissected separately. After turning over the fascia, the muscle was cut such that the base of the muscle flap was on the anterior side. Craniotomy, direct bypass, and encephalo-duro-synangiosis were performed conventionally. Only the temporal fascia was used for indirect revascularization and duraplasty. The muscle was replaced in the anatomically correct position after replacing the bone flap. RESULTS: We performed the aforementioned surgery on 18 (13 women and 5 men) consecutive patients (21 cerebral hemispheres) enrolled between 2012 and 2016. The average age was 28.7 years. The mean follow-up period was 31.6 months. In 17 patients (94%), the symptoms and cerebral blood flow improved. Digital subtraction angiography showed satisfactory angiogenesis from the temporal fascia. Depression in the temporal region and atrophy of the temporal muscle were negligible. CONCLUSIONS: This surgical technique provides good clinical and cosmetic outcomes. It may also be one of the good surgical treatments available for symptomatic moyamoya disease.

Stenotic changes of the posterior cerebral artery are a major contributing factor for cerebral infarction in moyamoya disease.

BACKGROUND: Some patients with moyamoya disease (MMD) show broad infarction with moderate internal carotid artery (ICA) stenosis, whereas others with complete ICA occlusion show no infarction. This suggests that other factors contribute to the occurrence of infarction. Contributing factors predictive of cerebral infarcts must be identified for the prevention of infarction and the consequent neurological deficits. METHODS: We examined data from 93 patients with confirmed MMD for the presence of infarction (n = 72), transient ischemic attack (TIA, n = 41), asymptomatic presentation (n = 51), or hemorrhage (n = 22) in 186 bilateral cerebral hemispheres. We analyzed the relationship between the occurrence of infarction and several clinical factors, such as steno-occlusive status or the site of the ICA and posterior cerebral artery (PCA). RESULTS: The incidence of PCA steno-occlusive lesions was significantly higher in infarcted (77.8%) than in non-infarcted hemispheres (TIA, 14.6%; asymptomatic, 9.8%; hemorrhagic 9.1%; P < 0.01). The steno-occlusive site of ICA was also a significant factor (P < 0.05). There was no significant correlation between the occurrence of infarction and the steno-occlusive status of the ICA or grade of the moyamoya vessels. Multivariate statistical analysis demonstrated that the PCA steno-occlusive changes were an important contributing factor for infarction (P < 0.0001). CONCLUSIONS: This is the multivariate statistical analysis study identifying PCA steno-occlusive lesions as the most important independent factor that is predictive to cerebral infarction in moyamoya patients. The prediction and inhibition of PCA steno-occlusive changes may help to prevent cerebral infarction.

Correction: The different pathogenesis of sporadic adenoma and adenocarcinoma in non-ampullary lesions of the proximal and distal duodenum.

[This corrects the article DOI: 10.18632/oncotarget.17051.].

Expression analyses of Phactr1 (phosphatase and actin regulator 1) during mouse brain development.

Phactr1 (Phosphatase and actin regulator 1) is abundantly expressed in the central nervous system and considered to regulate various neuronal processes through the regulation of protein phosphorylation and actin cytoskeletal organization. In this study, we prepared a specific antibody against Phactr1, anti-Phactr1, and carried out biochemical and morphological analyses of Phactr1 with mouse brain tissues. Western blotting analyses revealed that Phactr1 was expressed in a tissue-dependent profile in the young adult mouse and in a developmental stage-dependent manner in the mouse brain. In primary cultured hippocampal neurons, while Phactr1 was diffusely distributed in the nucleus and cytoplasm, it was visualized in axon and dendrites with partial colocalization with synapses. Phactr1 was also detected in the synaptosomal and postsynaptic density fractions in biochemical fractionation. Immunohistochemical analyses clarified that Phactr1 was differentially expressed in cortical neurons during corticogenesis; the protein was frequently accumulated in the nucleus at the embryonic stage while it came to diffusely distribute in the cell body at the prepubertal stage. The obtained results suggest that Phactr1 takes part in neuronal functions regulated in a spatiotemporal manner.

Long-term Prognosis after Extracranial-intracranial Bypass Surgery for Symptomatic Cerebrovascular Occlusive Disease.

Prognosis after extracranial-intracranial (EC-IC) bypass surgery has only been studied for a few years and the benefits of this procedure are still controversial. In this single-center retrospective study, we examined the long-term prognosis of patients who underwent EC-IC bypass surgery. Subjects were patients with symptomatic internal carotid artery or intracranial lesion occlusive disease who underwent EC-IC bypass surgery between 1991 and 2003. Of these, long-term prognosis was examined in 57 patients (39 male, 18 female; mean age, 61.8 years) who showed good surgical outcomes 30 days after bypass surgery, measured as a 0-2 on the modified Rankin Scale (mRS). They were divided into 2 groups (survivors and non-survivors) and were analyzed to identify factors effecting long-term survival after bypass surgery. Sixteen patients (28%), whose mean follow-up period (survival time) was 8.3±3.8 years, died after the bypass surgery. The average follow-up period for the survivors was 12.0±1.1 years, which was significantly longer than that for the non-survivors (P<0.0001). At surgery, the non-survivors (mean age 71.5 years) were significantly older than the survivors (P=0.0012). Pneumonia and other respiratory diseases were a frequent cause of death (31.2%), but death by cerebrovascular disease also occurred (12.5%). The rate of recurrent ischemic stroke was 28%, with no significant difference between groups (survivors vs. non-survivors: 31.2% vs. 26.1%, P= 0.82). In the absence of perioperative complications, the long-term prognosis of patients who underwent EC-IC bypass surgery was very good.

Promotion of cell proliferation by the proto-oncogene DEK enhances oral squamous cell carcinogenesis through field cancerization.

Oral squamous cell carcinoma (OSCC) develops through a multistep carcinogenic process involving field cancerization. The DEK gene is a proto-oncogene with functions in genetic and epigenetic modifications, and has oncogenic functions, including cellular proliferation, differentiation, and senescence. DEK overexpression is associated with malignancies; however, the functional roles of DEK overexpression are unclear. We demonstrated that DEK-expressing cells were significantly increased in human dysplasia/carcinoma in situ and OSCC. Furthermore, we generated ubiquitous and squamous cell-specific doxycycline (DOX)-inducible Dek mice (iDek and iDek-e mice respectively). Both DOX+ iDek and iDek-e mice did not show differences in the oral mucosa compared with DOX- mice. In the environment exposed to carcinogen, DOX-treated (DOX+) iDek mice showed field cancerization and OSCC development. Microarray analysis revealed that DEK overexpression was mediated by the upregulation of DNA replication- and cell cycle-related genes, particularly those related to the G1 /S transition. Tongue tumors overexpressing DEK showed increased proliferating cell nuclear antigen and elongator complex protein 3 expression. Our data suggest that DEK overexpression enhanced carcinogenesis, including field cancerization, in OSCC by stimulating the G1 /S phase transition and promoting DNA replication, providing important insights into the potential applications of DEK as a target in the treatment and prevention of OSCC.