Two rare cases of synchronous and metachronous colonic metastases in patients with advanced gastric cancer.

BACKGROUND: Patients with advanced gastric cancer (GC) may ultimately die because GC mostly leads to synchronous or metachronous metastasis. However, colonic metastasis of GC is extremely rare. According to a PubMed search of papers published from May 1968 to March 2017, only 21 patients with GC (10 patients from 10 case reports and 11 patients from a retrospective study) have been found to have colonic metastasis. In this report, we present two cases of synchronous and metachronous colonic metastases of advanced GC. CASE PRESENTATION: Two patients with advanced GC received a diagnosis of colonic metastasis based on colonoscopic findings and computed tomography images, and the diagnosis was confirmed through pathological immunohistochemical analysis. Herein, we describe the management and outcomes of these metastases. CONCLUSIONS: Submucosal swelling and segmental bowel wall thickening observed through colonoscopy in patients with advanced GC might indicate colonic metastasis.

Specificity protein 1-modulated superoxide dismutase 2 enhances temozolomide resistance in glioblastoma, which is independent of O6-methylguanine-DNA methyltransferase.

Acquisition of temozolomide (TMZ) resistance is a major factor leading to the failure of glioblastoma (GBM) treatment. The exact mechanism by which GBM evades TMZ toxicity is not always related to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT), and so remains unclear. In this study, TMZ-resistant variants derived from MGMT-negative GBM clinical samples and cell lines were studied, revealing there to be increased specificity protein 1 (Sp1) expression associated with reduced reactive oxygen species (ROS) accumulation following TMZ treatment. Analysis of gene expression databases along with cell studies identified the ROS scavenger superoxide dismutase 2 (SOD2) as being disease-related. SOD2 expression was also increased, and it was found to be co-expressed with Sp1 in TMZ-resistant cells. Investigation of the SOD2 promoter revealed Sp1 as a critical transcriptional activator that enhances SOD2 gene expression. Co-treatment with an Sp1 inhibitor restored the inhibitory effects of TMZ, and decreased SOD2 levels in TMZ-resistant cells. This treatment strategy restored susceptibility to TMZ in xenograft animals, leading to prolonged survival in an orthotopic model. Thus, our results suggest that Sp1 modulates ROS scavengers as a novel mechanism to increase cancer malignancy and resistance to chemotherapy. Inhibition of this pathway may represent a potential therapeutic target for restoring treatment susceptibility in GBM.

Electrophysiologic monitoring correlates of recurrent laryngeal nerve heat thermal injury in a porcine model.

OBJECTIVES/HYPOTHESIS: Thermal injury to the recurrent laryngeal nerve (RLN) may not be visually apparent and may go unrecognized intraoperatively. This study aimed to investigate the heat thermal tolerance of RLN and evaluate the electrophysiologic correlates of electromyographic (EMG) signal change during an acute RLN heat damage. STUDY DESIGN: Prospective porcine model with continuous intraoperative neuromonitoring (CIONM). METHODS: Ten pigs (20 RLNs) undergoing CIONM had their EMG tracings recorded and correlated with heated normal saline (NS) irrigation of varying temperature and duration. RESULTS: In the initial pilot study, the EMG was without change during incremental heated NS irrigation (40/45/50/55 °C for 60 seconds), but adverse EMG combined events (CE) (amplitude decrease with a concordant latency increase) occurred and degraded to loss of signal (LOS) (by 17.5 ± 1.3 seconds) when the temperature was elevated to 60 °C (n = 4). Another 16 RLNs were evaluated to further compare the EMG pattern after various degrees of thermal stress (60/70 °C for 30/20 seconds). Electromyographic recordings showed CEs and LOS in all RLNs, and only six of eight RLNs with 60 °C exposure showed slight EMG amplitude recovery (16%-35%) after 20 minutes. None of the injured nerve segments were visually apparent, but all were detectable by IONM. CONCLUSION: Sixty degrees Celsius is a critical temperature to cause RLN thermal injury. Continuous intraoperative neuromonitoring can be used as a tool for the early detection of acute thermal stress and may guide use of energy-based devices during thyroid procedures. LEVEL OF EVIDENCE: N/A.

Postoperative wound infection after posterior spinal instrumentation: analysis of long-term treatment outcomes.

PURPOSE: Postoperative spinal implant infection (PSII) places patients at risk for pseudarthrosis, correction loss, spondylodiscitis, adverse neurological sequelae, and even death; however, prognostic factors that predict long-term treatment outcomes have not been clearly investigated. In addition, few studies concerning the feasibility of reconstructing the failed spinal events have been published. METHODS: We performed a cohort study of 51 patients who contracted PSII in the posterolateral thoracolumbar region at a single tertiary center between March 1997 and May 2007. Forty-seven patients (92.2 %) had one or more medical problems. Isolated bacterial species, infection severity, treatment timing, and hosts' defense response were evaluated to assess their relationship with management outcomes. The use of implant salvage, or removal subsequent with a revision strategy depended on the patient's general conditions, infection control, and implant status for fusion. RESULTS: The most common infective culprit was Staphylococcus spp. found in 35 of 60 (58.3 %) isolates, including 20 methicillin-resistant species. Gram-negative bacilli and polymicrobial infection were found significantly in patients presenting early-onset, deep-site infection and myonecrosis. Prompt diagnosis and aggressive therapy were responsible for implant preservation in 41 of 51 cases (80.4 %), while implant removal noted in 10 cases (19.6 %) was attributed to delayed treatment and uncontrolled infection with implant loosening, correction loss, or late infection with spondylodesis. The number of employed debridements alone was not significantly correlated with successful implant preservation. Delayed treatment for infection >3 months significantly led to implant removal (p < 0.05) and a higher number of failed spinal events. Patients with significant comorbidities, malnutrition, severe trauma, neurological deficits, long-level instrumentation, and delayed treatment had poor outcomes. Sixteen patients (31.4 %) exhibited probable nonunion or pseudarthrosis, and eight symptomatic patients among them underwent successful revision surgery. CONCLUSIONS: Retention of the mechanically sound implants in early-onset infection permits fusion to occur, while delayed treatment, severe malnutrition and multiple comorbidities will most likely result in a lack of effectiveness in eradicating the infecting pathogens. Restoring optimal physiological conditions is imperative in high-risk patients to allow for further healing. When loosened screws cause peridiscal erosion and incapacitating motion pain, premature implant removal possibly results in failed fusion and correction loss. Reconstruction for a failed spinal event is feasible following infection control.

Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance.

BACKGROUND: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. RESULTS: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. CONCLUSIONS: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.

Xanthogranulomatous prostatitis: a rare entity resembling prostate adenocarcinoma with magnetic resonance image picture.

Granulomatous prostatitis, characterized by chronic granulomatous inflammation in the prostate, is rare. Xanthogranulomatous prostatitis is an even rarer granulomatous inflammation. We present a 74-year-old man who presented with lower urinary tract symptoms and elevated prostate specific antigen. A transrectal ultrasonography-guided prostate biopsy was performed, and pathological results showed foamy macrophage and inflammatory cell infiltrates, which were a distinctive feature of xanthogranulomatous prostatitis. We also present the characteristics of magnetic resonance imaging in xanthogranulomatous prostatitis which has never been previously described.

Ectomesenchymal chondromyxoid tumor of tongue.

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare entity of the dorsal tongue first described in 1995. Herein, we report a rare case of lingual ECMT in a 41-year-old man. Patient presented with an asymptomatic, small nodule (0.5 cm in diameter) in the anterior tongue. The pathological findings showed uni-lobular proliferation of fusiform cells, arranged in net-like sheets or swirls, in a chondromyxoid background. The tumor cells were immunoreactive for S-100 and glial fibrillary acidic protein (GFAP), but negative for epithelial markers. Familiarity with this entity helps pathologists make a correct diagnosis.

Novel phosphoinositide 3-kinase/mTOR dual inhibitor, NVP-BGT226, displays potent growth-inhibitory activity against human head and neck cancer cells in vitro and in vivo.

PURPOSE: Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling pathway frequently accounts for the tumorigenesis in head and neck cancer. To develop a new treatment, we investigated the effect of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in head and neck cancer cells. EXPERIMENTAL DESIGN: The in vitro antitumor effect of BGT226 was determined in various cancer cell lines. Animal models were also applied to examine drug potency. The inhibitory ability of BGT226 on the PI3K/AKT/mTOR signaling pathway was analyzed. RESULTS: The growth inhibition assay revealed that BGT226 was active against all tested cancer cell lines. Cross-resistance was not observed in the cisplatin-resistant cell line. The activation of the AKT/mTOR signal cascade was suppressed by BGT226 in a concentration- and time-dependent manner. Flow cytometric analysis revealed an accumulation of cells in the G(0)-G(1) phase with concomitant loss in the S-phase. Results of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and the analysis of caspase 3/7 and PARP indicated that BGT226 induced cancer cell death through an apoptosis-independent pathway. BGT226 induced autophagy as indicated by the aggregation and upregulation of the microtubule-associated protein light chain 3B-II, and p62 degradation. Gene silencing of Beclin1 or cotreatment of the autophagosome inhibitor, 3-methyladenine, inhibited the BGT226-induced autophagy and led to the retrieval of colony survival. In a xenografted animal model, BGT226 significantly delayed tumor growth in a dose-dependent manner, along with suppressed cytoplasmic expression of p-p70 S6 kinase and the presence of autophagosome formation. CONCLUSIONS: These data indicate that BGT226 is a potential drug in the treatment of head and neck cancer.